The clinical treatment of rheumatoid arthritis (RA) with first-line therapeutic drugs is hindered by the poor solubility, low bioavailability, off-target toxicity, and insufficient accumulation in inflamed joints. Liposomes have been shown to mitigate some of these limitations in drug delivery systems. However, the use of cholesterol to stabilize liposomal structures remains controversial due to its potential association with cardiovascular diseases. Here, we developed a novel liposome based on ginsenoside compound K (CK), which not only serves as an effective therapeutic agent for RA but also replaces cholesterol as a membrane stabilizer to address these challenges. Compared with conventional liposomes, ginsenoside CK Liposomes (CK@Lipo) are excellent nanoparticles, with CK stabilizing the liposomal structure and providing targeting functionality toward inflamed joints. When encapsulated with dexamethasone (Dex), CK@Lipo exhibits a synergistic anti-inflammatory effect, slowing the progression of RA. This study provides a theoretical basis for the future development of multifunctional novel ginsenoside CK@Lipo.

Peptide-based drug carriers with exceptional biodegradability offer promising avenues for tumor-targeted therapy. Nonetheless, almost all existing drug carriers harness receptor recognition to target tumors, which ultimately fall short in addressing tumor heterogeneity. Such a strategy requires intricate chemical modifications for carriers to selectively bind to specific receptors. While these modifications may induce long-term toxicity, tumor receptors are not absolutely specific but also exist in normal cells. Thus, precision therapeutic agents may inadvertently harm healthy cells as well. Tumors possess a distinctive weak acidic (pH 6.0-6.8) tumor microenvironment (TME) that contrasts with normal tissues (pH ~7.4). Hence, we developed a TME pH-triggered multilevel self-assembling peptide with simple modifications. The drug-encapsulating self-assembled peptide is size transformable from aggregates (~1.56 μm) at pH 7.4 to positively charged nanomicelles (~100 nm) at an acidic TME by protonation, which avoids being taken up by normal cells but could readily enter tumor cells, allowing TME pH-triggered tumor-specific therapy. This study establishes a breaking strategy of using peptide for TME-based tumor-specific treatment and advances the medical applications of peptide nanomaterials.

Breast cancer (BC) remains a significant global health challenge, with conventional treatment approaches such as surgery, chemotherapy, and radiation therapy. These approaches face limitations in targeting, toxicity, and efficacy. Liposomal drug delivery systems have emerged as promising tools for targeted breast cancer therapies. Liposomes can encapsulate both hydrophilic and hydrophobic drugs, improve drug distribution, and reduce the side effects. Passive targeting exploits the enhanced permeability and retention effect in tumor tissues, whereas active targeting employs small molecule ligands such as aptamers, folic acid (FA), transferrin, and monoclonal antibodies to specifically bind to overexpressed receptors on cancer cells. Aptamer-functionalized liposomes exhibit high specificity and affinity, folate and transferrin receptor targeting enhances cellular uptake and cytotoxicity, and antibody-conjugated liposomes improve drug delivery and efficacy by targeting specific antigens. Dual-responsive liposomes are sensitive to multiple stimuli and further enhance targeting precision. However, challenges remain, including tumor heterogeneity, limited penetration, and potential immunogenicity. Current research has focused on developing stable and effective formulations and exploring combination-targeting strategies to overcome these limitations. With further advancements, targeted liposomal drug delivery systems hold great promise in improving breast cancer treatment outcomes and reducing adverse effects.

Brain disorders, encompassing neurodegenerative conditions and intracranial neoplasms, present formidable obstacles in the realm of pharmacological delivery due to the existence of athe blood-brain barrier (BBB) and the restricted bioavailability of therapeutic agents. Alginate-derived nanoformulations have emerged as highly promising systems for drug delivery, offering attributes such as biocompatibility, regulated release, and improved targeting efficacies. This review investigates contemporary advancements in alginate-based nanoformulations, with a particular emphasis on their efficacy in surmounting obstacles to successful pharmacological delivery to the brain. Initially, we furnish a comprehensive overview of alginate, underscoring its pertinent properties, biomedical applications, and inherent limitations. Subsequently, the discourse progresses to strategies for nanoformulation, which encompass lipid-based, polymeric, and inorganic methodologies, with a focus on their benefits in relation to cerebral targeting. Moreover, this review entails the therapeutic potential of alginate-based nanoformulations in addressing significant neurological disorders, including Alzheimer's disease, Parkinson's disease, brain tumours, traumatic brain injury, epilepsy, and amyotrophic lateral sclerosis. By amalgamating cutting-edge nanotechnology with the distinctive properties of alginate, these formulations signify a promising pathway for the advancement of efficacious therapies aimed at brain targeting. Additionally, prospective research trajectories and challenges associated with the optimization of alginate-based nanocarriers for clinical applications are also elucidated.

Osteoarthritis (OA) associated with obesity is increasingly recognized as a distinct phenotype, driven by lipid metabolic imbalance and related inflammation. A particularly troublesome issue is that even after successfully correcting obesity, OA progression and lipid metabolic imbalance persist within the joint microenvironment, suggesting local lipid metabolism regulation as a potential treatment option. G-protein-coupled receptor 120 (GPR120), a primary receptor for long-chain fatty acids (including docosahexaenoic acid, DHA), has recently been found to play a pivotal role in regulating lipid homeostasis and suppressing inflammation. Here, we present ChD-FL/sgGPR, enabling dual endogenous-exogenous GPR120 activation. ChD-FL/sgGPR is a chondrocyte-biomimetic, fluorinated phenylboronic acid (FPBA)-modified ionizable liposome that codelivers DHA and a CRISPRa system comprising GPR120-specific sgRNA (single guide RNA) and dCas9-VPR mRNA (dead Cas9 fused to VP64-p65-Rta activator domain). Specifically, FPBA modification of liposomes enhances lysosomal escape and nuclear entry of RNA, while coextrusion with chondrocyte membranes facilitates cartilage-targeted delivery. In the coculture system of adipocytes and OA chondrocytes, ChD-FL/sgGPR significantly boosts chondrocytes GPR120 expression, facilitates lipid clearance via PPARγ signaling, and diminishes inflammatory mediators. In obese rat OA models, intra-articular injection of ChD-FL/sgGPR prolongs local retention, inhibits cartilage catabolism, and mitigates subchondral bone deterioration, collectively decelerating OA progression. By integrating CRISPR-mediated gene upregulation with DHA-induced receptor stimulation, this platform rebalances lipid metabolism in OA cartilage, offering a promising, mechanism-driven therapy for obesity-associated OA.

The pandemic caused by the SARS-CoV-2 virus has led scientists to intensify research on antiviral drugs and vaccines. As a result of these studies, it was observed that molnupiravir (MLP) and peramivir (PRV) could be used against pandemic. MLP affects SARS-CoV-2 replication, but it necessitates high doses, which can cause adverse effects in patients. PRV is a neuraminidase inhibitor, but the bioavailability of the drug after oral administration is very low. In this study, MLP-, PRV-loaded and combined liposome (COMB-Lipo) formulations were prepared via the thin film hydration method. Phospholipon 90 G-based formulations exhibited the most favorable characteristics, with a particle size of 111-145 nm, a polydispersity index (PDI) of less than 0.4, and a zeta potential (ZP) of 6-12 mV). Cell culture studies demonstrated that developed stable formulations are nontoxic to L929 and Vero E6 cells. Antiviral activity assessments against SARS-CoV-2 suggested the effectiveness of liposomes in inhibiting viral activity. These findings demonstrate that a possible synergistic effect of the newly developed sustained-release COMB-Lipo formulation is suggested with the complementary antiviral mechanisms of the combined agents. As a result, the therapeutic potential of co-delivery of anti-SARS-CoV-2 drugs for pulmonary application is considered a promising approach for long-acting treatment of COVID-19.

The efficient removal of refractory sulfides from fuels to achieve clean oil is a primary research focus in the petrochemical industry. This study introduces extraction and catalytic oxidation desulfurization (ECODS) as a technique for effective desulfurization. A cross-linking strategy was employed to construct structurally stable isotropic microreactors based on ionic liquid (IL)-modified liposomes (poly[MimA11, A11][heteropolyanions]), where exposed imidazolium cations anchor catalytic heteropolyanions (e.g., [PW12O40]3-) to ensure active site accessibility. In this interfacial catalytic reaction, the microreactor resembles an emulsified droplet with a spherical surface, significantly enhancing the catalytic interface. Additionally, the isotropic imidazolium cations of spherical vesicles provide the equivalent driving force for the attachment of heteropolyanions (such as [PW12O40]3- and [PMo12O40]3-), ensuring full exposure of active sites and reducing mass transfer resistance. The optimized poly[MimA11, A11][PW12O40] catalyst achieved complete dibenzothiophene (DBT) removal within 1.5 h and retained 92.4% efficiency after six cycles, demonstrating exceptional activity and recyclability. The morphology, structure, and properties of the microreactors were characterized, and optimal reaction conditions were established. Building on this foundation, the removal performances across various systems and sulfur-containing targets were assessed, thereby confirming the structure-activity relationship of this type of microreactor. Furthermore, the desulfurization mechanism was inferred from the identified oxidation products. Overall, this isotropic poly[MimA11, A11][heteropolyanion] demonstrates excellent desulfurization performance and holds significant potential for broad applications.

Iron is a crucial nutrient for our bodies, and its absence can lead to serious health issues like anemia. Unfortunately, oral iron supplements are frequently poorly absorbed and can lead to gastrointestinal discomfort due to iron's oxidative properties. However, using nanocarrier systems to encapsulate iron can mitigate these issues, enhancing its absorption and protecting it from oxidation, ultimately improving its effectiveness. In this research, niosomes loaded with iron sulfate were prepared using surfactant span 60 and Tween 80 via thin film hydration method. Cholesterol and 1-Dodecanol were used as stabilizers in different ratios. Physiochemical properties of niosomes loaded with iron sulfate, such as particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency (EE%), were investigated. The vesicle sizes varied between 453 and 3,276 nm, with encapsulation efficiencies ranging from 75 to 93%. The zeta potential measured between - 9.91 and 6.3 mV, while the particle size distribution (PDI) was observed to be between 0.004 and 0.59 in a phosphate buffer solution at pH 6.8. Ultimately, F1 Formula was established as the most effective formula, achieving an efficiency of 90.8%, a particle size of 546.8 nm, a zeta potential of 5.5, and a PDI of 0.57.

Silicosis is an occupational and irreversible interstitial lung disease, which is caused by the inhalation of respirable crystalline silica. Recent studies suggested that the senescence of endothelial cells is implicated in the pathogenesis of lung diseases. However, the role of senescent endothelial cells in silicosis remains poorly understood. By establishing multiple endothelial cell senescence models, and a silica-induced pulmonary fibrosis mouse model, we found that silica-induced endothelial cell senescence was accompanied by the increased expression of Galectin 3 (Gal3, gene name LGALS3). Mechanistically, silica-induced senescent cells synthesized a substantial amount of Gal3, which was subsequently released into the cellular microenvironment. Then, Gal3 directly binds to TGFBR1 on the cell membrane of lung fibroblasts and TLR4 on the macrophages, respectively. This cell communication facilitates the progression of silicosis by promoting fibroblast-myofibroblast transition (FMT) and NLRP3 inflammasome activation. Furthermore, Gal3 is regulated by the transcriptional regulatory factor CEBPB (CCAAT/ enhancer-binding protein beta) in senescent endothelial cells. In vivo, the administration of Lgals3 siRNA-loaded liposomes significantly ameliorated silica-induced pulmonary fibrosis. Collectively, our study demonstrated the critical role of endothelial cell senescence through the secretion of Gal3, which contributes to pulmonary fibrosis by promoting endothelial-fibroblast and endothelial-macrophage crosstalk.

Candida infections pose a significant health risk, prompting the search for new antifungal solutions due to the diminishing effectiveness of traditional drugs. Benzo[a]phenoxazine derivatives, described to have antimicrobial activity, are promising candidates. This study assessed the antifungal efficacy of five benzo[a]phenoxazine derivatives against Candida species for an effective antifungal strategy. The antifungal activity of various compounds against C. albicans, C. auris, C. glabrata C. parapsilosis, C. krusei and C. bracarensis was assessed using the yeast EUCAST protocol. C34, the most effective compound, was encapsulated in DODAB:MO liposomes. Antifungal efficacy, adhesion, and filamentation effects were compared for free and encapsulated C34. Cytotoxicity was determined via the MTT assay in the J774A.1 macrophage-like cell line, which was also employed to assess macrophage yeast killing in the presence of C34. The MIC values ranged from 3.75 to 60 μM, with C34 emerging as the most effective compound against all tested species/strains, specifically against fluconazole-resistant strains. Encapsulation in DODAB:MO liposomes improved C34's antifungal activity for most species, reducing MIC values. Both free and encapsulated C34 effectively reduced Candida adhesion and filamentation. Cytotoxicity assessment allowed the identification of a non-cytotoxic concentration of C34 that significantly enhanced macrophage activity against C. albicans. C34 displayed potent antifungal activity against various strains, including fluconazole-resistant ones as C. auris. It reduced key virulence factors, such as adhesion and filamentation, and enhanced macrophage-mediated clearance, making it a compound of interest for further development as a potential therapeutic option.

Personalized treatment strategies have greatly improved the efficacy of anticancer drugs. Nanocarriers, especially liposomes, function as excellent platform for the delivery of both hydrophilic and hydrophobic agents. iRGD is a peptide composed of 9-amino acid denoted as (iRGDP), enhances selective and intratumoral delivery of anticancer drugs. Trastuzumab (TMAB), mainly targets HER2-positive advanced stage breast cancer is an FDA-approved monoclonal antibody. Gefitinib (GEB) is an anticancer drug, effective against metastatic breast cancer (MBC), while Lycorine hydrochloride (LCOH), a naturally derived compound, possess both anti-inflammatory and anticancer properties. This research is mainly emphasizing on the preparation of GEB and LCOH-entrapped TPGS-COOH coated-liposomes, camouflaged with an antibody (TMAB) and cyclic peptide (iRGDP) for targeted delivery in MBC therapy. The developed multifunctional liposomes were studied for extensive in vitro cell line studies on MCF-7 cells. The half-maximum inhibitory concentration (IC-50) values of GEB and LCOH co-loaded single functionalized liposome (SFL) (iRGDP-LiP, and TMAB-LiP) and dual-functionalized liposome (DFL) (iRGDP-TMAB-LiP) on MCF-7 cells were 1.04 ± 0.023 μg/mL, 0.71 ± 0.018 μg/mL, and 0.56 ± 0.028 μg/mL, respectively. Inverted confocal laser scanning microscopy (ICLSM) revealed enhanced cellular internalization in SFL and DFL-treated groups tagged with coumarin-6 and rhodamine-B dye as compared to conventional liposome. The scratch assay revealed a marked reduction in cell migration, while DAPI staining confirmed enhanced nuclear condensation (NC) and nuclear fragmentation (NF) in SFL and DFL-treated groups. Moreover, flow cytometry demonstrated enhanced early and late apoptosis in SFL and DFL groups. These findings indicate that GEB and LCOH co-loaded multifunctional liposome holds promise as a multifaceted therapeutic approach for MBC therapy.

Cancer treatments such as surgery and chemotherapy have several limitations, including ineffectiveness against large or persistent tumors, high relapse rates, drug toxicity, and non-specificity of therapy. Researchers are exploring advanced strategies for treating this life-threatening disease to address these challenges. One promising approach is targeted drug delivery using prodrugs or surface modification with receptor-specific moieties for active or passive targeting. While various drug delivery systems have shown potential for reaching hepatic cells, nano-carriers offer significant size, distribution, and targetability advantages. Engineered nanocarriers can be customized to achieve effective and safe targeting of tumors by manipulating physical characteristics such as particle size or attaching receptor-specific ligands. This method is particularly advantageous in treating liver cancer by targeting specific hepatocyte receptors and enzymatic pathways for both passive and active therapeutic strategies. It highlights the epidemiology of liver cancer and provides an in-depth analysis of the various targeting approaches, including prodrugs, liposomes, magneto-liposomes, micelles, glycol-dendrimers, magnetic nanoparticles, chylomicron-based emulsion, and quantum dots surface modification with receptor-specific moieties. The insights from this review can be immensely significant for preclinical and clinical researchers working towards developing effective treatments for liver cancer. By utilizing these novel strategies, we can overcome the limitations of conventional therapies and offer better outcomes for liver cancer patients.

Periodontitis (PD) is a chronic gum illness that may be hard to cure for a number of reasons, including the fact that no one knows what causes it, the side effects of anti-microbial treatment, and how various kinds of bacteria interact with one another. As a result, novel therapeutic approaches for PD treatment must be developed. Additionally, supplementary antibacterial regimens, including local and systemic medication administration of chemical agents, are necessary for deep pockets to assist with mechanical debridement of tooth surfaces. As our knowledge of periodontal disease and drug delivery systems (DDSs) grows, new targeted delivery systems like extracellular vesicles, lipid-based nanoparticles (NPs), metallic NPs, and polymer NPs have been developed. These systems aim to improve the targeting and precision of PD treatments while reducing the systemic side effects of antibiotics. Nanozymes, photodermal therapy, antibacterial metallic NPs, and traditional PD therapies have all been reviewed in this research. Medicinal herbs, antibiotics, photothermal therapy, nanozymes, antibacterial metallic NPs, and conventional therapies for PD have all been examined in this research. After that, we reviewed the key features of many innovative DDSs and how they worked for PD therapy. Finally, we have discussed the advantages and disadvantages of these DDSs.

Current cancer therapies including immunotherapy and chemotherapy produce adverse side effects that demand improved drug distribution methods. Research shows that thermosensitive chitosan/pectin-based hydrogels serve as an effective platform technology for drug delivery during cancer therapy because of their ability to control drug release at specific locations. The hydrogels perform temperature-triggered sol-gel phase shifts which enables prolonged drug delivery together with minimal toxic side effects. The biocompatible and biodegradable properties of these materials enable solutions against drug resistance and tumour heterogeneity challenges. Studies have demonstrated that these hydrogels enhance drug bioavailability, extend circulation time, and improve tumour targeting, leading to increased therapeutic efficacy and reduced systemic toxicity. Their ability to sustain drug release and penetrate tumour microenvironments makes them a promising strategy for overcoming drug resistance and tumour heterogeneity. Their ability to reproduce native tissue properties poses challenges that scientists must address through improved structural optimization approaches. The combination of latest nanotechnology innovations and interdisciplinary studies has sped up the creation of chitosan/pectin hydrogels for cancer treatment applications. This review highlights the significant advancements and demonstrated effectiveness of thermosensitive chitosan/pectin hydrogels in cancer treatment by exploring their design parameters alongside their drug release behaviour while discussing their potential medical applications.

Naringenin may play a role in browning by increasing thermogenic gene expression. In this study, we encapsulated naringenin using a liposomal formulation and examined the effects of both free and liposomal naringenin on white adipose tissue browning in C57BL6/J mice. In the first phase of the study, naringenin was encapsulated by the liposome method, which is biocompatible and biodegradable. The physical and chemical properties of liposomal naringenin were tested. In the second phase, a total of 48 six-week-old mice were divided into two main groups: prevention and recovery. Each main group was divided into four subgroups: nano-naringenin, void, free-naringenin, and control. The prevention group received a high-fat diet for 10 weeks along with weekly intravenous injections of 20 µM naringenin. On the other hand, the recovery group was first subjected to a high-fat diet for 10 weeks, followed by an additional 10 weeks of the same diet, along with weekly intravenous injections of 20 µM naringenin. Body weight was measured once per week, and brown adipose tissue, inguinal white adipose tissue, and serum samples were collected from each mouse. The mean particle size, polydispersity index and zeta potential values of liposomal naringenin were ∼207 nm, 0.35, and -27 mV, respectively. The encapsulation and loading efficiencies of liposomal naringenin were 94.6 and 19.2%, respectively. Liposomal naringenin exhibited sustained-release behavior, while free naringenin showed a burst-release profile. Liposomal naringenin showed the best physical stability in light and at 4 °C, while free naringenin was more chemically stable in light and at 4 and 22 °C. Free and liposomal naringenin did not significantly reduce weight gain. In the prevention group, liposomal naringenin increased PRDM16 gene expression in inguinal white adipose tissue 4.29 times more than free naringenin (p = 0.010). However, neither formulation significantly altered the expression levels of other browning or adipogenesis markers in the tissues. The results suggest that free naringenin can be efficiently encapsulated in biocompatible and biodegradable nanoparticles. Further research is needed to better understand the physiological effects of liposomal naringenin.

Manganese-based STING-activating tumor immunotherapy faces limitations due to T cell exhaustion. Mitochondrial dysfunction is a key factor contributing to T cell exhaustion. Modulating mitochondrial function during manganese-based immunotherapy offers a promising strategy to reverse T cell exhaustion. Spermidine (SPD) enhances mitochondrial function in T cells, making the co-delivery of Mn and SPD a potential therapeutic approach. However, intravenous co-delivery is hindered by the rapid formation of MnO(OH)₂ precipitates. In this study, liposomes were employed as nano-reactors to facilitate the reaction between pre-loaded Mn²⁺ and O₂ in the presence of SPD, forming MnO(OH)₂ precipitates within the liposomes. These liposomes function as nanofactories, further processing MnO(OH)₂ under the regulation of the tumor microenvironment (TME) and delivering Mn, SPD, and O₂. Beyond activating the STING pathway in dendritic cells, L@Mn@SPD alleviates TME hypoxia and effectively reverses CD8⁺ T cell exhaustion. In vivo, L@Mn@SPD achieved a 2.44-fold increase in tumor suppression compared to MnCl₂, along with a 47% rise in CD8⁺ T cell infiltration, a 62.1% reduction in PD-1 expression, and a 110% increase in IFN-γ secretion. This STING-activating nanofactory provides a promising strategy to enhance manganese-based tumor immunotherapy by addressing mitochondrial dysfunction in exhausted T cells.

It has been reported that miR-29a-3p played a part in series neurological disorders. However, it remains unclear whether miR-29a-3p participate in the pathological mechanism in hypoxia-ischemia (HI) brain injury. In this study, we detected the change of miR-29a-3p level in the ipsilateral cortex following HI brain injury and found that miR-29a-3p was significantly increased at 3 days in the ipsilateral cortex following HI insult in neonatal mice. Therefore, we further explored the role of miR-29a-3p in HI brain injury and its molecular mechanism. The results showed that miR-29a-3p mimics attenuated and miR-29a-3p antagomir aggravated brain infarction volume at 3 days following HI insult. We further found that overexpression of miR-29a-3p also suppressed apoptosis and neuroinflammation, reduced synaptic loss and prevent HI-induced microglial morphological changes 3 days following HI insult. Neurobehavioral tests revealed that overexpression of miR-29a-3p could improve both short-term and long-term behavioral defects after HI injury. Furthermore, we proved that miR-29a-3p targets B-cell translocation gene 2 (BTG2) and further inhibits the expression of Bax by luciferase reporter assay and qRT-PCR. Moreover, overexpression of miR-29a-3p, by applying liposomes through intranasal route, could also achieve the same therapeutic effect in HI injury. Our data showed that by inhibiting BTG2/Bax, increasing level of miR-29a-3p might serve as a strategy to prevent brain damage and behavioral deficiency in HI.

Chemotherapy is one of the primary modalities for the treatment of malignant diseases. The outcomes, however, are different between tumors of various origins, which hinder clinical applications. The advantages of chemotherapies in patients with hematological lesions are more obvious than those seen in solid tumors. This might be attributed to the availability of drug concentration and exposure time. Based on this phenomenon, we hypothesis that localized drug administration is expected to be more potential for solid tumors, particularly for the residual tumors in post-operative "window period". The presence of residual tumors after surgical resection are the major factors leading to tumor recurrence after surgery. The methods of dealing with this problem are yet to be found. Conventional chemotherapies are scarcely applied in the post-surgical window period due to their unselected and unexpected side effects. This article studied the advantages and disadvantages of prominent formulations currently utilized in the field of local implantation in cancer treatment, with the notable superiority of injectable hydrogel platforms being most appealing. These platforms not only enhance wound healing of the patients with less side effects, during the "window period" following tumor surgery, but also effectively eradicate residual tumors by facilitating the establishment of a favorable microenvironment. Additionally, the challenges seen in this field and future directions are discussed, which is expected to provide insights for pharmaceutical professionals and clinical applications.

Lipid nanoparticles (LNPs) represent a versatile delivery platform proposed for a wide range of therapies based on nucleic acids, including microRNA (miRNAs). The ability of LNPs to encapsulate and protect RNA from degradation, as well as their ability to promote cellular uptake, has led to their clinical use with the approval of RNA-based medicinal products, i.e., COVID vaccines. In this context, a growing number of LNP formulations with improved transfection and biocompatibility are under development, requiring rapid, sensitive, and robust quality control tests, e.g., for the quantification of the encapsulated RNA. Nowadays, classical analytical approaches such as fluorescence, ultraviolet-visible (UV-vis) spectrophotometry, and chromatography are mainly used for the quantification of the encapsulated drug. However, the user-friendly and cost-effective quantification of the encapsulation efficacy within LNPs represents an important research focus, as it would allow monitoring of the amount of encapsulated RNA, thus providing immediate quality control. In this work, we present the adaptation of an electrochemical strip to quantify the encapsulation of a miRNA, i.e., miR-218, whose antitumor effect has been widely reported in the literature within LNPs. We provide a rapid and sensitive method to assess the concentrations of miRNA actually encapsulated, obtaining satisfactory agreement compared to the traditional fluorimetric approach. Specifically, the platform is based on a commercial gold-screen-printed electrode modified with a DNA probe designed to be fully complementary to the target miRNA-218. The electrochemical system was successfully combined with a 3D-printed chamber that allowed the use of multiple electrodes simultaneously and the use of Triton X-100 surfactant to disrupt the LNPs and release the encapsulated miRNA-218 achieving a detection limit as low as 1 nM.

Degeneration of intervertebral discs is a significant factor in chronic lower back pain, impacting millions annually. Existing studies propose a potential link between lipids and disc disease, though causal relationships remain unclear. The objective of this study is to explore the causal connections between lipids, lower back pain, disc degeneration, and the risk of sciatica In this research, we utilized a comprehensive GWAS dataset encompassing 179 lipid traits to explore the causal connections between lipids and the susceptibility to conditions such as lower back pain (LBP), intervertebral disc degeneration (IVDD), and sciatica. To establish causality, we employed two-sample Mendelian randomization, supplemented by Bayesian model averaging for verification. Our assessment of diversity and mutual influence involved Cochran's Q test, MR-Egger intercept assessment, and MR-PRESSO. Additionally, we performed a sensitivity analysis by systematically excluding individual elements to gauge their impact on outcomes in Mendelian randomization. Lastly, bidirectional Mendelian randomization was conducted to explore potential inverse associations between lipids and IVDD. Analyzing 179 lipidomic features as exposures and IVDD, LBP, and sciatica as outcomes, this study reveals significant causal relationships of glycerophospholipids, sterols, and glycerolipids with the risk of IVDD, LBP, and sciatica. Phosphatidylcholine, triglycerides, and sterols consistently exerted risk influences on IVDD, while phosphatidylethanolamine (O-16:1_18:2) among glycerophospholipids exhibited a protective effect (OR: 0.927-0.998, P < 0.05). Regarding LBP, sphingomyelin (d38:2) in sphingolipids demonstrated a protective effect (OR: 0.925-0.997, P < 0.05). For sciatica, triglycerides exhibited a risk influence, with varying effects observed for phosphatidylcholine and sterols with different molecular structures. Notably, sterol ester (27:1/16:1) consistently showed a risk effect across all three conditions. Our research provides valuable insights into how certain lipids are linked to the risks of LBP, IVDD, and sciatica. Our findings indicate that phosphatidylcholine and triglycerides may increase the incidence of IVDD, LBP, and sciatica, suggesting potential adverse effects. In contrast, sphingomyelin appears to reduce the occurrence of LBP and sciatica, indicating a protective role. Sterol esters also show a protective effect against sciatica; however, the sterol ester (27:1/16:1) consistently demonstrates a detrimental impact on IVDD, LBP, and sciatica. Additionally, our study underscores the intricate nature of lipid metabolism concerning IVDD, LBP, and sciatica. It uncovers a range of structural variations among lipids and explores how these variations may lead to different effects across various molecular subtypes.

The feasibility of engineering the sophisticated hybrid drug delivery platforms through the integration of phospholipid vesicles within a matrix of amyloid suspensions has been evaluated. Utilizing the equilibrium dialysis methodology and spectrofluorometric technique, the quantitative analysis of doxorubicin (DOX) encapsulation capacity of diverse phospholipid assemblies, amyloid suspensions, and their corresponding composite systems has been performed. Our findings revealed that the incorporation of negatively charged cardiolipin (CL) into phosphatidylcholine (PC) lipid vesicles significantly enhances DOX encapsulation and retention, while the addition of amyloid fibrils to charged liposomes has minimal impact on the drug binding. The neutral PC liposomes modified with insulin and lysozyme fibrillar suspensions exhibited improved doxorubicin encapsulation and retention compared to unmodified liposomes, thereby displaying a potential for reduced toxicity and prolonged drug action in vivo. Notably, amyloid fibrils alone were found to demonstrate the lower degree of DOX encapsulation and retention as compared to liposomes. Fluorimetric analysis suggests that the presence of insulin and lysozyme fibrils alters the microenvironment of DOX towards a more hydrophobic which is consistent with deeper bilayer penetration. Cumulative data from release kinetics and retention studies along with fluorescence measurements suggest that PC liposome-insulin fibril composites represent the most promising DOX nanocarriers, combining enhanced drug encapsulation, structural stability, and optimal drug location within the bilayer. The results obtained provide valuable insights into the design of protein-lipid nanomaterials for enhanced drug delivery, offering promising avenues for the development of more effective and targeted therapeutic strategies.

Radiotherapy (RT) is a relevant treatment for head and neck squamous cell carcinoma (HNSCC) patients but radioresistance, which depends on DNA damage response (DDR), restrains outcome. Therefore, manipulating DDR by small molecule inhibitors (SMI) is a promising treatment option. The main DNA double strand break (DSB) repair mechanisms in healthy mammalian cells are homologous recombination (HR) and non-homologous end joining (NHEJ). It is known that HR is already often impaired in tumors because of cancerous transitions. Therefore, additionally inhibiting NHEJ is a possibility to specifically target tumor cells and spare healthy tissue, which has the alternative DSB repair mechanism available. We treated HNSCC and healthy fibroblast cell lines with 30 µM of the ligase IV inhibitor SCR130 and a single dose of 2 Gy (Gy) ionizing radiation (IR) to investigate the inhibitor's radiosensitizing effect. In short, the effect of SCR130 in combination with IR on cell death, clonogenicity, and DNA damage is limited and highly cell line specific. Nevertheless, SCR130 increases the number of cells in G0/G1 phase concomitant with gained p21 expression consistently. We suggest that SCR130 in combination with IR has anti-proliferative effects, but an escape of the cells by upregulation of ligase IV resulting from the treatment is possible.

Silk fibroin materials are promising for use in controlled drug delivery in the field of tissue engineering and biomedical applications thanks to silk's generally established biocompatibility and tunable properties for implants and drug storage. Several factors must be considered in the materials design, including material format, drug properties and release kinetics, and the activity and stability of the drug after release. While numerous reviews described silk-based DDS that demonstrated controllable in vitro release, success in vivo has been limited, especially in some material formats. This review therefore aims to provide insight into the current material format and functionalization strategies to maximize in vivo performance by describing the in vivo activity of recently developed silk drug delivery systems. The review also aims to provide a fresh perspective on the suitable format and functionalization strategies for a target biomedical application. Based on the release behavior of drugs in various material formats, silk films, foams, and microneedles were better suited to serve as scaffolds for cell regeneration and improved recovery rate for biomedical applications involving wound healing and tissue engineering. Gels and particles could be incorporated within the films and foams but the purpose would be to serve as additional physical barriers towards drug diffusion in these types of application. For drugs or therapeutics that target internal organs (i.e. brain, liver, intestines, etc.), gels and particles were mainly used due to their size. In the event that the material format selection based on the target application does not contribute a lot to the prolonged release of drugs or therapeutic agents, hybrid functionalization strategies were adapted to make the surface chemistry of the material more responsive to the environmental stimuli for a more tunable silk DDS.

Amantadine hydrochloride (AMH) is a repurposed moiety of anti-viral category having significant response against Parkinsonism. Nasal route is linked with the direct delivery of drugs to brain through olfactory and trigeminal nerves. The mucociliary clearance is the major obstacle for effective delivery of drugs. The optimized formulation was coated with chitosan (CH) to enhance the residence time of formulation in the nasal cavity. The optimized NLCs exhibited particle size of 174.2 ± 1.5 nm, PDI of 0.131 ± 0.019, zeta potential of -27.52 ± 3.29 mV, EE of 74.06 ± 2.3 %, and nasal flux of 66.03 ± 0.9 μg/cm2/h. FTIR analysis revealed AMH-excipient compatibility and encapsulation of AMH into NLCs. XRD analysis confirmed no polymorphic transition in the developed NLCs. Drug release exhibited sustained release of AMH (71.01 ± 2.19 %) up to 24 h. Ex vivo study (goat nasal mucosa) showed 3.22 folds enhanced permeability of AMH from AMH-NLCs in comparison to AMH-Sol. The recommended storage condition for AMH-NLCs was found to be 25 °C/60 % RH. AMH-NLCs showed high cell viability (88.23 ± 7.49 %) in comparison to AMH-Sol (62.14 ± 6.81 %) on H2O2 induced PC12 cells at a concentration level of 100 μg/ml. In vivo studies exhibited effectiveness of CH-AMH-NLCs and AMH-NLCs and showed increased response when compared with amantadine solution (pure form) and marketed formulation.

In this study, we reported a cationic azobenzene (Azo) tag to increase the retention of camptothecin (CPT) prodrugs in liposomes driven by π-π stacking interaction between Azo. Compared with a cationic CPT prodrug without Azo, the liposome-encapsulating Azo-linked CPT prodrugs (AzoCPT-Lips) exhibited slower prodrug leakage in plasma and a longer blood circulation time in mice. The AzoCPT-Lips had a high encapsulation efficiency (95%), loading capacity (20%, by weight), and good storage stability. The AzoCPT was efficiently taken up by 4T1 tumor cells (100-fold higher than CPT) and readily converted into active CPT in the cytoplasm to exert 10-fold higher cytotoxicity than free CPT. More importantly, AzoCPT-Lips resulted in 5-20 times higher tumor distribution of active CPT than that of CPT solution or those in other tissues, which further led to more potent antitumor activity and lower toxicities in the 4T1 breast cancer xenograft. Such a cationic Azo tag represents an effective strategy for developing liposomal antitumor drugs with improved antitumor efficacy.

Periodontal diseases affect tooth-supporting structure producing bone-defects. Well-known bone-regeneration techniques are expensive, sophisticated and maybe immunogenic. We aimed at emerging a cost-effective, easily manufactured and safe nano-bone graft containing the natural-polyphenol resveratrol (RSV) which was reported to have in-vivo bone-regeneration efficacy. However, RSV suffers from poor solubility, bioavailability and photosensitivity. Its incorporation into a nanocarrier system could resolve these problems. RSV liposomes were prepared using Phosal® in different ratios and the optimized formula showed multilamellar vesicles, PS (126.1 nm), PDI (0.3017), ZP (-34.5 mV), %EE (90.86 %), with a sustained-release pattern. Then it was lyophilized and recharacterized and the obtained pliable mass (RSV-Ph75-LyoMan) lyo-nanograft suited its application into bone-defects performed in rabbits' tibiae. Histomorphometric quantitative analyses of bone sections micrographs were performed to verify RSV anti-inflammatory action, by counting bone marrow-infiltrating lymphocytes, and to explore the phases of bone-regeneration process exerted by RSV, by counting osteocytes, osteoblasts and osteoclasts and further confirmed by assessing bone-thickness, using ImageJ-software. This was done after 3, 6, 9 weeks of applying either placebo or RSV-Ph75-LyoMan. A significant decrease in lymphocytes' counts in RSV-Ph75-LyoMan compared to control-sites at the assessed time points was obtained. Further, RSV-Ph75-LyoMan significantly accelerated bone-healing and regeneration processes as concluded from the differential osteocytes, osteoblasts and osteoclasts counts. Consequently, a significant increase in bone-thickness in (RSV-Ph75-LyoMan)-treated-sites; 68.25 ± 3.45, 109.5 ± 5.49, and 148.2 ± 7.25 µm after 3, 6, 9 weeks was obtained, with a significant difference when compared to control-sites; 40.05 ± 2.21, 45.23 ± 1.87 and 46.57 ± 1.45 µm, respectively. Histological studies confirmed trabecular-remolding after 9 weeks in (RSV-Ph75-LyoMan)-treated-sites. RSV-Ph75-LyoMan lyo-nanograft is promising for treatment of osseous bony-defects in rabbits.

A novel combination delivery approach entrapping Sorafenib inside a nanoliposome bilayer and Doxorubicin within the aqueous core to achieve the broad-spectrum synergistic chemotherapeutic effect. DOX-SOR liposomes were synthesized by thin film hydration and characterized using UV-visible spectroscopy, Fourier Transform Infrared Spectroscopy, Dynamic Light Scattering, Fluorescence, and Scanning Electron Microscopy, followed by cytotoxicity assessments. Nanoliposomes demonstrated effective loading and encapsulation of Doxorubicin (10.23% ± 0.65 and 89.65% ± 0.52) and Sorafenib (10.42% ± 0.50 and 85.35% ± 0.72) with a 165 nm ± 1.34 mean diameter, -15.2 ± 1.78 zeta potential, and 75% ± 1.92 of cumulative release. In vitro analysis of nanoliposomes demonstrated biocompatibility up to 250 µg/mL concentration (p < 0.05), enhanced intracellular localization in Hep2c cell lines, 91% ± 1.72 cytotoxic effects (p < 0.0001) with IC50 up to 127µg/mL, 21% ± 0.89 cell viability with 85% apoptosis (p < 0.0001) using flow cytometer. This study presents a promising treatment approach using a multidrug-loaded nanoliposomes for broad-spectrum synergistic chemotherapy.

Human Papillomavirus (HPV) is the main cause of cervical cancer, and formulations have been widely used to treat vaginal lesions caused by HPV. Herein, liposomes with acridine orange derivative C8 were produced and functionalized with AT11 aptamer. Subsequently, they were incorporated into a formulation, prepared based on the universal placebo formulation, which included Thymus vulgaris (TEO) or Origanum vulgare (OEO) essential oils. The formulation was technologically characterized and permeation of C8 into vaginal tissue was determined. To assess its biological effect, cell viability and internalization tests were carried out using the MTT assay and confocal microscopy, respectively, and antimicrobial susceptibility was also assessed. The prepared formulations were able to internalize cells and reduce cell viability, especially in cancer cell lines. Additionally, formulations showed promising antibacterial and antifungal effects. The effect of the formulation containing TEO and the C8 AT11 liposomes was also tested in vivo in HPV16 transgenic and wild type mice. Briefly, the formulation proved to be safe for animals and presented some therapeutic potential, namely through the reduction of ear epithelial cells' proliferation. Overall, results suggest that essential oils can increase the anticancer potential of liposomes with associated C8 and AT11 promotes their selectivity towards cancer cells.

Although oxidative stress is the main pathophysiology of the development of diabetic neuropathy, oral administration of antioxidants has given disappointing results. Here, we hypothesized that local delivery of antioxidants would provide protective effects on Schwann cells due to the high concentration of local lesions. We prepared alpha-tocopherol (ATF)-loaded liposomes and tested their skin penetration after sonication. An in vitro study using IMS-32 cells was conducted to determine the level of reactive oxygen species (ROS) scavenging effects of ATF-liposomes. ATF reduced ROS in high-glucose-exposed IMS-32 cells in a dosedependent manner. ATF-liposomes also reduced the ROS level in vitro and ultrasound irradiation enhanced delivery to the dermis in porcine ear skin. This study showed that it is feasible to deliver ATF through the skin and can effectively reduce ROS. This model is worthy of development for clinical use.

Bladder cancer (BC) in the urinary system remains one of the most prevalent malignancies with high recurrence rate globally. Current treatment schemes against BC such as surgery, chemotherapy, and radiotherapy have substantial limitations including side effects, drug resistance, and poor tumor targeting. Considering the above-mentioned challenges, nanotechnology has become a current research hotspot, particularly liposome-based drug delivery systems, which offer promising novel therapeutic strategies aimed at reducing systemic toxicity, overcoming drug resistance, and enhancing drug targeting. This review systematically elaborates the current research progress on liposomal drug delivery systems in BC treatment, focusing on their application in chemotherapy, immunotherapy, and gene therapy. Additionally, we provide a comprehensive assessment of the benefits and limitations of liposome nanocarriers used in BC treatment. The advanced targeting strategies and combination treatments via liposomal therapies are also discussed, demonstrating that liposomal formulations have great potential application value in the treatment of BC owing to their superior bioavailability, stability, and targeting and minimal adverse effects.

Objectives: Hot-melt extrusion (HME) offers a solvent-free, scalable approach for manufacturing pharmaceutical co-crystals (CCs), aligning with the industry's shift to continuous manufacturing (CM). However, challenges like undefined yield optimization, insufficient risk management, and limited process analytical technology (PAT) integration hinder its industrial application. This study aimed to develop a proof-of-concept HME platform for CCs, assess process risks, and evaluate PAT-enabled monitoring to facilitate robust production. Methods: Using carbamazepine (CBZ) and nicotinamide (NIC) as model compounds, an HME platform compatible with PAT tools was established. A systematic risk assessment identified five key risk domains: materials, machinery, measurement, methods, and other factors. A Box-Behnken design of experiments (DoE) evaluated the impact of screw speed, temperature, and mixing sections on CC quality. Near-infrared (NIR) spectroscopy monitored CBZ-NIC co-crystal formation in real time during HME process. Results: DoE revealed temperature and number of mixing sections significantly influenced particle size (D50: 2.0-4.0 μm), while screw speed affected efficiency. NIR spectroscopy detected a unique CC absorption peak at 5008.3 cm⁻¹, enabling real-time structural monitoring with high accuracy (R² = 0.9999). Risk assessment highlighted material attributes, process parameters, and equipment design as critical factors affecting CC formation. All experimental batches yielded ≥ 94% pure CCs with no residual starting materials, demonstrating process reproducibility and robustness. Conclusions: Overall, this work successfully established a continuous hot-melt extrusion (HME) process for manufacturing CBZ-NIC co-crystals, offering critical insights into material, equipment, and process parameters while implementing robust in-line NIR monitoring for real-time quality control. Additionally, this work provides interpretable insights and serves as a basis for future machine learning (ML)-driven studies.

The inherent complexity of cancer proliferation and malignancy cannot be addressed by the conventional approach of relying on high doses of a single powerful anticancer agent, which is associated with poor efficacy, higher toxicity, and the development of drug resistance. Multiple drug therapy (MDT) rationally designed to target tumor heterogeneity, block alternative survival pathways, modulate the tumor microenvironment, and reduce toxicities would be a viable solution against cancer. Liposomes are the most suitable carrier for anticancer MDT due to their ability to encapsulate both hydrophilic and hydrophobic agents, biocompatibility, and controlled release properties; however, an adequate manufacturing method is important for effective co-encapsulation. Microfluidics involves the manipulation of fluids at the microscale for the controlled synthesis of liposomes with desirable properties. This work critically reviews the use of microfluidics for the synthesis of anticancer MDT liposomes. MDT success not only relies on the identification of synergistic dose combinations of the anticancer modalities but also warrants the loading of multiple therapeutic entities within liposomes in optimal ratios, the protection of the drugs by the nanocarrier during systemic circulation, and the synchronous release at the target site in the same pattern as confirmed in preliminary efficacy studies. Prospects have been identified for the bench-to-bedside translation of anticancer MDT liposomes using microfluidics.

Gene delivery offers great potential for treating various diseases, yet its success requires overcoming several biological barriers. These hurdles span from extracellular degradation, reaching the target cells, and inefficient cellular uptake to endosomal entrapment, cytoplasmic transport, nuclear entry, and transcription limitations. Viruses and non-viral vectors deal with these barriers via different mechanisms. Viral vectors, such as adenoviruses, adeno-associated viruses, and lentiviruses use natural mechanisms to efficiently deliver genetic material but face limitations including immunogenicity, cargo capacity, and production complexity. Nonviral vectors, including lipid nanoparticles, polymers, and protein-based systems, offer scalable and safer alternatives but often fall short in overcoming intracellular barriers and achieving high transfection efficiencies. Recent advancements in vector engineering have partially overcome several of these challenges. Ionizable lipids improve endosomal escape while minimizing toxicity. Biodegradable polymers balance efficacy with safety, and engineered protein systems, inspired by viral or bacterial entry mechanisms, integrate multifunctionality for enhanced delivery. Despite these advances, challenges, particularly in achieving robust in vivo translatability, scalability, and reduced immunogenicity, remain. This review synthesizes current knowledge of cellular barriers and the approaches to overcome them, providing a roadmap for designing more efficient gene delivery systems. By addressing these barriers, the field can advance toward safer, and more effective therapies.

Nanotechnology and nanomaterials have emerged as promising tools for the delivery of anti-tumor drug cisplatin (CDDP). However, concerns exist regarding potential toxicity and cost-effectiveness, limiting their clinical applications. In contrast, plant-derived exosomes (PDEs), as natural nanovesicles, offer significant advantages as drug delivery carriers due to their large-scale production, biocompatibility, and ability to efficiently transport therapeutic drug across cellular barriers. In this work, we established a ginseng-derived exosome (G-Exo)-based CDDP delivery system (G-CDDP) and evaluated its anti-tumor efficacy both in vitro and in vivo. The results demonstrated that G-CDDP effectively targeted tumor site, inhibiting the proliferation and migration and promoting apoptosis in U-87MG tumor cells. Notably, the amount of CDDP in G-CDDP required for achieving the same cytotoxic effect on tumor cells was 12.66 times lower than that of free CDDP. In U-87MG tumor-bearing mice, G-CDDP effectively targeted tumor sites and exhibited significant therapeutic effect. Collectively, these findings highlight the potent anti-tumor activity of G-CDDP at reduced CDDP dosage, positioning it as a promising and efficient alternative to conventional drug treatments in clinical settings.

Background: Hypertension (HTN) is recognized as a major risk factor for cardiovascular disease, chronic kidney disease, and peripheral artery disease. Valsartan (VAL), an angiotensin receptor blocker drug for hypertension, has been limited due to its poor solubility and poor absorption from the GIT, which leads to low oral bioavailability. Objectives/Method: In the present research, firstly, VAL-loaded nanoliposomes were formulated and optimized using the Box-Behnken design (BBD). Optimized VAL-nanoliposomes were physically characterized and their fate was examined by scanning and transmission microscopy, DSC, FTIR, XRD, and ex vivo studies using rat skin. In vitro studies using human keratinocyte (HaCaT) cells showed a decrease in cell viability as the liposome concentration increased. Secondly, the formulation of VAL-loaded nanoliposomes was integrated into dissolvable microneedles (DMNs) to deliver the VAL transdermally, crossing the skin barrier for better systemic delivery. Results: The optimized nanoliposomes showed a vesicle size of 150.23 (0.47) nm, a ZP of -23.37 (0.50) mV, and an EE% of 94.72 (0.44)%. The DMNs were fabricated using a ratio of biodegradable polymers, sodium alginate (SA), and hydroxypropyl methylcellulose (HPMC). The resulting VAL-LP-DMNs exhibited sharp pyramidal microneedles, adequate mechanical properties, effective skin insertion capability, and rapid dissolution of the microneedles in rat skin. In the ex vivo analysis, the transdermal flux of VAL was significantly (5.36 (0.39) μg/cm2/h) improved by VAL-LP-DMNs. The enhancement ratio of the VAL-LP-DMNs was 1.85. In conclusion, liposomes combined with DMNs have shown high potential and bright prospects as carriers for the transdermal delivery of VAL. Conclusions: These DMNs can be explored in studies focused on in vivo evaluations to confirm their safety, pharmacokinetics profile, and pharmacodynamic efficacy.

Pulmonary arterial hypertension (PAH) is a progressive, life-threatening condition characterized by increased pulmonary vascular resistance and right ventricular hypertrophy (RVH). Current treatments primarily alleviate symptoms but do not effectively target the underlying molecular mechanisms driving the disease. This study aimed to evaluate the therapeutic potential of R8-modified liposomal delivery of circNFXL1, a circular RNA, in a mouse model of PAH.

R8-circNFXL1 liposomes were synthesized and characterized for their physicochemical properties, including encapsulation efficiency. PAH was induced in C57BL/6 mice using a combination of subcutaneous Su5416 administration and hypoxic exposure. Intranasal delivery of R8-circNFXL1 was performed, and therapeutic effects were assessed using echocardiography and hemodynamic measurements. Molecular mechanisms were explored through analysis of the miR-29b/Kcnb1 axis, a regulatory pathway in PAH.

The R8-circNFXL1 liposomes demonstrated optimal physicochemical properties, including high encapsulation efficiency. Treatment with R8-circNFXL1 significantly reduced RVH, improved cardiac function, and mitigated pulmonary vascular remodeling compared to untreated PAH controls. Molecular analysis revealed that R8-circNFXL1 modulated the miR-29b/Kcnb1 axis, providing insights into its mechanism of action.

R8-circNFXL1 liposomes offer a promising, targeted therapeutic strategy for PAH by addressing underlying molecular mechanisms. This approach has potential implications for developing alternative treatments to improve disease management and outcomes in PAH.

Curcumin is a natural polyphenol extracted from plants that can interact with various molecular targets, including antioxidant, antibacterial, anticancer, and anti-aging activities. Due to its variety of pharmacological activities and large margin pf safety, curcumin has been used in the prevention and treatment of various diseases, such as Alzheimer's, heart, and rheumatic immune diseases. To develop curcumin eye drops that can be used as antioxidant and antibacterial agents after phacoemulsification, we have designed a nano-based drug delivery system to improve curcumin bioavailability and duration of action. We successfully prepared zeolitic imidazolate framework-8 (ZIF-8) coated with chitosan-liposome (Cur@ZIF-8/CS-Lip) for curcumin delivery. It can release curcumin for over 20 hin vitroand exhibits excellent biosafety, antioxidant, and antibacterial activities. Therefore, we hypothesized that Cur@ZIF-8/CS-Lip could reduce the incidence of oxidative stress and infection after cataract surgery.

Designing effective drug therapies requires balancing competing objectives, such as therapeutic efficacy, safety, and cost efficiency-a task that poses significant challenges for conventional optimization methods. To address this, we propose the multi-objective spider-wasp optimizer (MOSWO), a novel approach uniquely emulating the cooperative predation dynamics between spiders and wasps observed in nature. MOSWO integrates adaptive mechanisms for exploration and exploitation to resolve complex trade-offs in multiobjective drug design. Unlike existing approaches, the algorithm employs a dynamic population-partitioning strategy inspired by predator-prey interactions, enabling efficient Pareto frontier discovery. We validate MOSWO's performance through extensive experiments on synthetic benchmarks and real-world case studies spanning antiviral and antibiotic therapies. Results demonstrate that MOSWO surpasses state-of-the-art methods (NSGA-II, MOEA/D, MOGWO, and MOPSO), achieving 11% higher hypervolume scores, 8% lower inverted generational distance scores, 9% higher spread scores, a 30% faster convergence, and superior robustness against noisy biological datasets. The framework's adaptability to diverse therapeutic scenarios underscores its potential as a transformative tool for computational pharmacology.

3-D multi-faceted, nano-globular PAMAM dendritic skeleton is a highly significant polymer that offers applications in biomedical, industrial, environmental and agricultural fields. This is mainly due to its enhanced properties, including adjustable surface functionalities, biocompatibility, non-toxicity, high uniformity and reduced cytotoxicity, as well as its numerous internal cavities. This trait inspires further exploration and advancements in tailoring approaches. The implementation of deliberate strategic modifications in the morphological characteristics of PAMAM is crucial through chemical and biological interventions, in addition to its therapeutic advancements. Thus, the production of peripheral groups remains a prominent and highly advanced technique in molecular fabrication, aimed at boosting the potential of PAMAM conjugates. Currently, there exist numerous dendritic-hybrid materials, despite the widespread use of PAMAM-conjugated frameworks as drug delivery systems, which are well regarded for their efficacy in enhancing potency through the incorporation of surface functions. This paper provides a comprehensive review of recent progress in the design and assembly of various components of PAMAM conjugates, focusing on their unique formulations. The review encompasses synthetic methodologies, a thorough evaluation of their applicability, and an analysis of their potential functions in the context of Drug Delivery Systems (DDS) in the current period.

Signal transducer and activator of transcription 3 (STAT3) is a critical transcription factor involved in multiple physiological and pathological processes. While STAT3 plays an essential role in homeostasis, its persistent activation has been implicated in the pathogenesis of various diseases, particularly cancer, bone-related diseases, autoimmune disorders, inflammatory diseases, cardiovascular diseases, and neurodegenerative conditions. The interleukin-6/Janus kinase (JAK)/STAT3 signaling axis is central to STAT3 activation, influencing tumor microenvironment remodeling, angiogenesis, immune evasion, and therapy resistance. Despite extensive research, the precise mechanisms underlying dysregulated STAT3 signaling in disease progression remain incompletely understood, and no United States Food and Drug Administration (USFDA)-approved direct STAT3 inhibitors currently exist. This review provides a comprehensive evaluation of STAT3's role in health and disease, emphasizing its involvement in cancer stem cell maintenance, metastasis, inflammation, and drug resistance. We systematically discuss therapeutic strategies, including JAK inhibitors (tofacitinib, ruxolitinib), Src Homology 2 domain inhibitors (S3I-201, STATTIC), antisense oligonucleotides (AZD9150), and nanomedicine-based drug delivery systems, which enhance specificity and bioavailability while reducing toxicity. By integrating molecular mechanisms, disease pathology, and emerging therapeutic interventions, this review fills a critical knowledge gap in STAT3-targeted therapy. Our insights into STAT3 signaling crosstalk, epigenetic regulation, and resistance mechanisms offer a foundation for developing next-generation STAT3 inhibitors with greater clinical efficacy and translational potential.

GOx-mediated glucose depletion offers an alternative noninvasive strategy for tumor therapy, but its lower catalytic activity in vivo limits its clinical application. Herein, we designed a temperature-sensitive nano-GOx (NG) that was constructed by gold nanorods chemically modified with GOx (AuNRs-GOx) and coated with temperature-sensitive lipids. The chemical linkage could maintain the natural conformation of GOx, ensuring that NG exerted powerful catalytic activity within the tumor and initiated antitumor immune response through moderate starvation and mild photothermal therapy (mPTT) to coregulating dendritic cells (DCs) and tumor-associated macrophages (TAMs). Ulteriorly, VTNG was obtained by NG coloading with verteporfin (VP) and evofosfamide (TH-302). VTNG demonstrated temperature-sensitive triggered drug release when exposed to near-infrared laser irradiation. NG exacerbated the degree of TME hypoxia and facilitated the activation of TH-302. Meanwhile, VP enhanced tumor cell sensitivity by decreasing the stemness of the tumor cells, thus realizing the effective killing of tumor cells and further enhancing the therapeutic effect of NG. Notably, VTNG had a significant antitumor effect in melanoma models compared with first-line melanoma therapy and formed an immune memory effect. In conclusion, VTNG provided an effective approach to enhance the therapeutic effect of GOx for tumor treatment.