Cardiovascular diseases (CVDs) are vital causes of global mortality. Apart from lifestyle intervention like exercise for high-risk groups or patients at early period, various medical interventions such as percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery have been clinically used to reduce progression and prevalence of CVDs. However, invasive surgery risk and severe complications still contribute to ventricular remodeling, even heart failure. Innovations in nanomedicines have fueled impressive medical advances, representing a CVD therapeutic alternative. Currently, clinical translation of nanomedicines from bench to bedside continues to suffer unpredictable biosafety and orchestrated behavior mechanism, which, if appropriately addressed, might pave the way for their clinical implementation in the future. While state-of-the-art advances in CVDs nanomedicines are widely summarized in this review, the focus lies on urgent preclinical concerns and is transitioned to the ongoing clinical trials including stem cells-based, extracellular vesicles (EV)-based, gene, and Chimeric Antigen Receptor T (CAR T) cell therapy whose clinically applicable potential in CVD therapy will hopefully provide first answers. Overall, this review aims to provide a concise but comprehensive understanding of perspectives and challenges of CVDs nanomedicines, especially from a clinical perspective.

Traumatic brain injury and Alzheimer's disease share pathological similarities, including neuronal loss, amyloid-β deposition, tau hyperphosphorylation, blood-brain barrier dysfunction, neuroinflammation, and cognitive deficits. Furthermore, traumatic brain injury can exacerbate Alzheimer's disease-like pathologies, potentially leading to the development of Alzheimer's disease. Nanocarriers offer a potential solution by facilitating the delivery of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease. Unlike traditional approaches to neuroregeneration, this is a molecular-targeted strategy, thus avoiding non-specific drug actions. This review focuses on the use of nanocarrier systems for the efficient and precise delivery of siRNAs, discussing the advantages, challenges, and future directions. In principle, siRNAs have the potential to target all genes and non-targetable proteins, holding significant promise for treating various diseases. Among the various therapeutic approaches currently available for neurological diseases, siRNA gene silencing can precisely "turn off" the expression of any gene at the genetic level, thus radically inhibiting disease progression; however, a significant challenge lies in delivering siRNAs across the blood-brain barrier. Nanoparticles have received increasing attention as an innovative drug delivery tool for the treatment of brain diseases. They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier, targeted drug delivery, enhanced drug stability, and multifunctional therapy. The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach. Although this strategy is still in the preclinical exploration stage, it is expected to achieve clinical translation in the future, creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.

Despite the increasing global prevalence of neurological disorders, the development of nanoparticle (NP) technologies for brain-targeted therapies confronts considerable challenges. One of the key obstacles in treating brain diseases is the blood-brain barrier (BBB), which restricts the penetration of NP-based therapies into the brain. To address this issue, NPs can be installed with specific ligands or bioengineered to boost their precision and efficacy in targeting brain-diseased cells by navigating across the BBB, ultimately improving patient treatment outcomes. At the outset of this review, we highlighted the critical role of ligand-functionalized or bioengineered NPs in treating brain diseases from a clinical perspective. We then identified the key obstacles and challenges NPs encounter during brain delivery, including immune clearance, capture by the reticuloendothelial system (RES), the BBB, and the complex post-BBB microenvironment. Following this, we overviewed the recent progress in NPs engineering, focusing on ligand-functionalization or bionic designs to enable active BBB transcytosis and targeted delivery to brain-diseased cells. Lastly, we summarized the critical challenges hindering clinical translation, including scalability issues and off-target effects, while outlining future opportunities for designing cutting-edge brain delivery technologies.

The rapid advancement of nanobiotechnology has resulted in the development of numerous targeted nanoformulations and sophisticated nanobiorobots for biomedical applications. Despite the potential of nanostructures to improve drug delivery and therapeutic efficacy, their clinical application is still constrained by insufficient accumulation in tumor tissues. Current methodologies result in only an average of 0.6 % of administered nanoparticles reaching tumors, prompting the development of innovative strategies to improve targeting and influence the pharmacokinetics and pharmacodynamics of drugs. One such approach is two-step targeting, which includes either the concept of tumor pre-targeting with specific recognizing elements or the stimuli-sensitive activation of nanostructures. This review critically evaluates advancements in two-step drug delivery systems utilizing nanobiotechnology for targeted cancer therapy. For instance, two-step delivery based on the pre-targeting concept involves an initial injection of targeting molecules that bind to tumor-specific antigens, followed by the administration of drug-loaded nanocarriers modified with complementary adaptors. This approach enhances nanoparticle accumulation in tumors and improves therapeutic outcomes by increasing interaction avidity and overcoming steric hindrances. We critically assess existing adaptor systems for two-step drug delivery and synthesize findings from various studies demonstrating their efficacy in both in vitro and in vivo settings, while addressing challenges in clinical translation. We also explore future directions for developing novel adaptor systems to enhance two-step delivery mechanisms. This review aims to contribute to optimizing nanobiotechnology in oncology for more effective cancer therapies.

Cancer develops as a result of changes in both genetic and epigenetic mechanisms, which lead to the activation of oncogenes and the suppression of tumor suppressor genes. Despite advancements in cancer treatments, the primary approach still involves a combination of chemotherapy, radiotherapy, and surgery, typically providing a median survival of approximately five years for patients. Unfortunately, these therapeutic interventions often bring about substantial side effects and toxicities, significantly impacting the overall quality of life for individuals undergoing treatment. Therefore, urgent need of research required which comes up with effective treatment of cancer. This review explores the transformative role of Proteolysis-Targeting Chimeras (PROTACs) in cancer therapy. PROTACs, an innovative drug development strategy, utilize the cell's protein degradation machinery to selectively eliminate disease-causing proteins. The review covers the historical background, mechanism of action, design, and structure of PROTACs, emphasizing their precision in targeting oncogenic proteins. The discussion extends to the challenges, nanotechnology applications, and ongoing clinical trials, showcasing promising results and clinical progress. The review concludes with insights into patents, future directions, and the potential impact of PROTACs in addressing dysregulated protein expression across various diseases. Overall, it provides a concise yet comprehensive overview for researchers, clinicians, and industry professionals involved in developing targeted therapies.

Treating urinary tract infections (UTIs) effectively is a difficult task due to the emergence of antibiotic-resistant bacteria and limited antibiotic access to intracellular bacteria within the bladder lining. Numerous studies of the antibiotics-nanodiamonds (NDs) synthesis and their inhibitory effect on bacteria have been performed previously. However, their effectiveness and toxicity in cell-based and animal infection models remain unclear. In this study, we presented the utilization of biopolymer-coated nanodiamonds for the delivery of tetracycline (TET) to the intracellular bacterial communities within the bladder cells using an intravesical delivery approach, aiming to effectively treat UTIs. Compared with antibiotics alone, the TET-loaded ND-based carrier system significantly improved the clearance of intracellular bacteria in the infected cell and animal models. Moreover, the intravesical delivery avoids the potential toxic effects from NDs accumulation in the organs, and minimizes the loss of the drugs during delivery. These results offer a promising strategy to treat chronic infections and prevent the recurrence of urinary tract infections (rUTIs).

Tracking nanoparticles' location is imperative for understanding cellular interactions, pharmacokinetics, and biodistribution. DiD is a lipophilic dye commonly used to label nanoparticles for trafficking studies. Herein, we show that DiD micelles form in polymer NP solutions during synthesis and can lead to false positive results in downstream assays. Potential methods to remove these micelles are also described.

Ovarian cancer is one of the leading causes of cancer-related deaths in women, with limited progress in treatments despite decades of research. Common treatment protocols rely on surgical removal of tumors and chemotherapy drugs, such as paclitaxel and carboplatin, which are capable of reaching cancer cells throughout the body. However, the effectiveness of these drugs is often limited due to toxic reactions in patients, nonspecific drug distribution affecting healthy cells, and the development of treatment resistance. In this study, we introduce a polybasic nanogel system composed of poly(diethylaminoethyl methacrylate-co-cyclohexyl methacrylate)-g-poly(ethylene glycol) designed for the targeted co-delivery of paclitaxel and carboplatin directly to ovarian cancer cells. These nanogel systems can respond to the cellular microenvironment to achieve controlled, on-demand drug release, reducing off-target effects and enhancing therapeutic uptake. Additionally, we investigated nanoparticle degradation and controlled drug release as a function of various crosslinkers, including tetraethylene glycol dimethacrylate, bis(2-methacryloyl)oxyethyl disulfide, poly(lactic acid)-b-poly(ethylene glycol)-b-poly(lactic acid)dimethacrylate, and polycaprolactone dimethacrylate. Our results, using OVCAR-3 human ovarian cancer cells, demonstrated that this dual-delivery system outperformed free drugs in inducing cancer cell death, representing a promising advance in the field of nanoparticle-based therapies for ovarian cancer. By loading two chemotherapeutic agents into a single, environmentally responsive particle, this approach shows the potential to overcome common resistance mechanisms and achieve more effective tumor suppression. In summary, by delivering chemotherapy more precisely, it may be possible to enhance therapeutic outcomes while minimizing toxicity and nonspecific drug distribution, ultimately improving patient quality of life.

Chimeric antigen receptor (CAR) T cell immunotherapy relies on CAR targeting of tumor-associated antigens; however, heterogenous antigen expression, interpatient variation and off-tumor expression by healthy cells remain barriers. Here we develop synthetic antigens to sensitize solid tumors for recognition and elimination by CAR T cells. Unlike tumor-associated antigens, we design synthetic antigens that are orthogonal to endogenous proteins to eliminate off-tumor targeting and that have a small genetic footprint to facilitate efficient tumor delivery to tumors by lipid nanoparticles. Using a camelid single-domain antibody (VHH) as a synthetic antigen, we show that adoptive transfer of anti-VHH CAR T cells to female mice bearing VHH-expressing tumors reduced tumor burden in multiple syngeneic and xenograft models of cancer, improved survival, induced epitope spread, protected against tumor rechallenge and mitigated antigen escape in heterogenous tumors. Our work supports the in situ delivery of synthetic antigens to treat antigen-low or antigen-negative tumors with CAR T cells.

Eliciting a robust immune response against tumors is often hampered by the inadequate presence of effective antigen presenting cells and their suboptimal ability to present antigens within the immunosuppressive tumor microenvironment. Here, we report a cascade antigen relay strategy integrating antigen capturing nanoparticles (AC-NPs) and migratory type 1 conventional dendritic cells (cDC1s), named Antigen Capturing nanoparticle Transformed Dendritic Cell therapy (ACT-DC), to facilitate in situ immunization. AC-NPs are engineered to capture antigens directly from the tumor and facilitate their delivery to adoptively transferred migratory cDC1s, enhancing antigen presentation to the lymph nodes and reshaping the tumor microenvironment. Our findings suggest that ACT-DC improves in situ antigen collection, triggers a robust systemic immune response without the need for exogenous antigens, and transforms the tumor environment into a more "immune-hot" state. In multiple tumor models including colon cancer, melanoma, and glioma, ACT-DC in combination with immune checkpoint inhibitors eliminates primary tumors in 50-100% of treated mice and effectively rejects two separate tumor rechallenges. Collectively, ACT-DC could provide a broadly effective approach for in situ cancer immunization and tumor microenvironment modulation.

Diabetes mellitus is a chronic metabolic disorder, which is characterized by high blood glucose levels, and this can lead to serious diabetic complications. According to the World Health Organization, approximately 830 million adults worldwide are living with diabetes in 2024, with its prevalence continuing to rise steadily over the years. To treat this disease, researchers have developed a variety of first-line drugs, such as sulfonylureas and thiazolidinediones. Despite their long clinical use, there are still many drawbacks and limitations. One of the main drawbacks is low bioavailability, this causes the diabetic patients to take the drugs frequently to lower the blood glucose levels continuously. Some patients may have to take multiple drugs to increase the effectiveness of lowering blood glucose levels. To address these limitations, nano-based drug delivery systems have emerged to overcome these problems. It has emerged as a promising approach for diabetes management, which offers controlled and localized release of anti-diabetic drugs, thus enhancing therapeutic efficacy. This review discusses recent advances in the field of nano-based drug delivery systems for diabetes management, safety and toxicity profiles of anti-diabetic drugs, and future perspectives for the development of nanomedicine in diabetic treatment. Literature search was conducted using electronic databases, and only English literatures were used and published between 2014 and 2024. Recent advancements in nanotechnology have facilitated the development of various nanocarriers, such as polymeric carrier nanoparticles, nanoliposomes, nanocrystals, nanosuspension and inorganic nanoparticles, which enhance drug stability, bioavailability, and efficacy. These systems can deliver anti-diabetic drugs and natural compounds more effectively, thereby minimizing side effects and improving patient compliance. As the field continues to evolve, the successful clinical implementation of nanodrugs could revolutionize the management of diabetes and improve the quality of life for millions of diabetic patients worldwide.

Multi-drug nanomedicine is gaining momentum for co-delivering more than one drug to the same site at the same time. Our analysis of 273 pre-clinical tumour growth inhibition studies shows that multi-drug nanotherapy outperforms single-drug therapy, multi-drug combination therapy, and single-drug nanotherapy by 43, 29 and 30%, respectively. Combination nanotherapy also results in the best overall survival rates, with 56% of studies demonstrating complete or partial survival, versus 20-37% for control regimens. Within the multi-drug nanomedicine groups, we analysed the effect of (co-)administration schedule and strategy, passive versus active targeting, nanocarrier material and the type of therapeutic agent. Most importantly, it was found that co-encapsulating two different drugs in the same nanoformulation reduces tumour growth by a further 19% compared with the combination of two individually encapsulated nanomedicines. We finally show that the benefit of multi-drug nanotherapy is consistently observed across different cancer types, in sensitive and resistant tumours, and in xenograft and allograft models. Altogether, this meta-analysis substantiates the value of multi-drug nanomedicine as a potent strategy to improve cancer therapy.

Gold Nanoparticles (GNPs) play a pivotal role in nanobiotechnology because of their distinct physicochemical traits, such as optical properties, compatibility with biological systems, and their ability to be easily functionalized. The top-down and bottom-up approaches are for the synthesis of GNPs. There are various chemical, physical, and green synthesis techniques, such as chemical reduction, seed-mediated growth, physical ablation method, pyrolysis, sputtering, etc. are some methods for the synthesis of GNPs. The use of plants, algae, fungi, and other microorganisms has recently arisen as a new approach for the eco-friendly synthesis with precise control over NP size, shape, and surface properties. The functionalization strategies involving biomolecules, polymers, and ligands enhance their stability and target specificity, facilitating their integration into biosensors. The detection of biomolecules, pathogens, and environmental toxins with high sensitivity and accuracy is facilitated by multiple signals such as localized surface plasmon resonance (LSPR), alterations in color, and electrochemical characteristics. Furthermore, their role in point-of-care diagnostics, drug delivery, and imaging underscores their versatility in biomedical applications. This review provides a comprehensive overview of recent advancements in the synthesis, functionalization, and GNPs-based biosensors. In addition, the review highlights recent advancements, challenges, and future prospects of GNPs in biosensing and nanomedicine, offering an understanding of diagnostics and therapeutic monitoring. The key challenges include stability, reproducibility, and scalability, and the future focuses on green synthesis with enhanced sensitivity and multiplexed biosensing applications.

Drug resistance is a serious problem for human health worldwide. Day by day this drug resistance is increasing and creating an anxious situation for the treatment of both cancer and infectious diseases caused by pathogenic microorganisms. Researchers are trying to solve this terrible situation to overcome drug resistance. Biosynthesized gold nanoparticles (AuNPs) could be a promising agent for controlling drug-resistant pathogenic microorganisms and cancer cells. AuNPs can be synthesized via chemical and physical approaches, carrying many threats to the ecosystem. Green synthesis of AuNPs using biological agents such as plants and microbes is the most fascinating and attractive alternative to physicochemical synthesis as it offers many advantages, such as simplicity, non-toxicity, cost-effectiveness, and eco-friendliness. Plant extracts contain numerous biomolecules, and microorganisms produce various metabolites that act as reducing, capping, and stabilizing agents during the synthesis of AuNPs. The characterization of green-synthesized AuNPs has been conducted using multiple instruments including UV-Vis spectrophotometry (UV-Vis), transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray diffraction (XRD), DLS, and Fourier transform infrared spectroscopy (FT-IR). AuNPs have detrimental effects on bacterial and cancer cells via the disruption of cell membranes, fragmentation of DNA, production of reactive oxygen species, and impairment of metabolism. The biocompatibility and biosafety of synthesized AuNPs must be investigated using a proper in vitro and in vivo screening model system. In this review, we have emphasized the green, facile, and eco-friendly synthesis of AuNPs using plants and microorganisms and their potential antimicrobial and anticancer applications and highlighted their antibacterial and anticancer mechanisms. This study demonstrates that green-synthesized AuNPs may potentially be used to control pathogenic bacteria as well as cancer cells.

Background/Objectives: Gene therapy has emerged as a promising strategy for treating a wide range of diseases. However, a major challenge remains in developing efficient and safe delivery systems for genetic material. Nanoparticles, particularly chitosan nanoparticles (CNPs), have gained significant attention as a potential solution. This study focuses on designing a SARS-CoV-2 plasmid DNA (pDNA) conjugated with CNPs and evaluating its in vitro delivery efficiency. Methods: The Omicron Spike DNA sequence was inserted into the pIRES2-eGFP expression vector, and CNPs were synthesized with optimized physicochemical properties to enhance stability, cellular uptake, and transfection efficiency. The conjugate was characterized using UV-Vis, FT-IR, DLS, and TEM techniques. Transfection efficiency was assessed and compared to the commercially available TurboFect reagent as a control. Results: CNPs-pDNA polyplexes with an average size of 159.0 ± 33.1 nm (TEM), a zeta potential of +19.7 ± 0.3 mV, and 100% ± 0.0 encapsulation efficiency were developed as a non-viral delivery system. CNPs efficiently serve as a delivery vehicle for the constructed pDNA without altering cell morphology, achieving transfection efficiencies of 62-74%, compared to 55-70% for TurboFect. Furthermore, RT-qPCR confirmed the expression of Spike mRNA, and Western blot assays validated the expression of Spike protein. Notably, Spike protein expression from CNPs was found to be two-fold higher than the control at 96 h post-transfection. Conclusions: These findings suggest that CNPs are a promising and versatile platform for delivering genetic material. Importantly, this study highlights the intrinsic properties of chitosan, without the use of additional ligands, as a key factor in achieving efficient gene delivery.

The use of nanoparticles in nuclear medicine is paradoxical. While several nanoformulations, such as 99mTc colloids, have been used for diagnosis for decades, only a few new radionanomedicines have been able to reach the market, despite extensive preclinical efforts. This contradiction is dictated by the unique features of nanoparticles, such as (potential) prolonged circulation times, slow compartment exchanges, and large accumulations in the mononuclear phagocyte system, which allow for certain specific applications while preventing others. In this review, we discuss the development and clinical application of radiolabeled nanoparticles as imaging agents for disease diagnosis and patient stratification, as well as their promise and potential to be used as next-generation formulations to improve the efficacy of radiotherapy.

Silver nanoparticles (AgNPs) are increasingly known to have anticancer effects, but few studies have examined their adverse effects, so the underlying mechanisms are not yet fully understood. The current study investigated the critical influence of AgNPs on angiogenesis in 4T1 breast cancer-bearing mice.

The sub-lethal dose of AgNPs (0.25 mg/kg) was carried out. Female BALB/c mice (N = 35) were divided into 7 groups; normal control, cancer control, AgNPs control (one dose of (0.25 mg/kg) AgNPs), single dose AgNPs before cancer, single dose AgNPs after cancer, 5 doses AgNPs after cancer, and doxorubicin. 4T1 breast cancer cell induction was performed subcutaneously on the left flank. Intraperitoneal (IP) administration of AgNPs and doxorubicin was carried out for all studied groups.

Weight gain was normal in all study groups except the doxorubicin-treated group. Administering AgNPs before cancer induction promotes tumorigenesis, raises MMP-2 and MMP-9 activity, and increases CD31 and Ki67 expression. The cancer control group experienced the same outcomes. On the other hand, depending on the administered doses, the injection of AgNPs after tumor induction resulted in a notable decrease in tumor volume. In the doxorubicin-treated group, similar results were observed, while a dose of AgNPs‌ before cancer induction lead to increasing tumor volume compared to the cancer control group. The differences of biochemical markers including LDH, ALP, AST, ALT, BUN, and Cr between different groups were not significant. Significant differences were seen among all studied groups except doxorubicin and single dose AgNPs before cancer groups for serum TAC levels.

It appears that AgNPs are considered a double-edged sword in the fight against cancer. AgNPs not only have anti-cancer effects on tumor size and angiogenesis, but they also might have cancer-stimulating roles. To confirm this conclusion, more detailed investigations are needed.

mTORopathies represent a group of neurodevelopmental disorders linked to dysregulated mTOR signaling, resulting in conditions such as tuberous sclerosis complex, focal cortical dysplasia, hemimegalencephaly, and Smith-Kingsmore Syndrome. These disorders often manifest with epilepsy, cognitive impairments, and, in some cases, structural brain anomalies. The mTOR pathway, a central regulator of cell growth and metabolism, plays a crucial role in brain development, where its hyperactivation leads to abnormal neuroplasticity, tumor formation, and heightened neuronal excitability. Current treatments primarily rely on mTOR inhibitors, such as rapamycin, which reduce seizure frequency and tumor size but fail to address underlying genetic causes. Advances in gene editing, particularly via CRISPR/Cas9, offer promising avenues for precision therapies targeting the genetic mutations driving mTORopathies. New delivery systems, including viral and non-viral vectors, aim to enhance the specificity and efficacy of these therapies, potentially transforming the management of these disorders. While gene editing holds curative potential, challenges remain concerning delivery, long-term safety, and ethical considerations. Continued research into mTOR mechanisms and innovative gene therapies may pave the way for transformative, personalized treatments for patients affected by these complex neurodevelopmental conditions.

Synthetic cells, such as giant unilamellar vesicles, can be engineered to detect and release chemical signals to control target cell behavior. However, control over target-cell populations is limited due to poor spatial or temporal resolution and the inability of synthetic cells to deliver patterned signals. Here, 3D-printed picoliter droplet networks are described that direct gene expression in underlying bacterial populations by patterned release of a chemical signal with temporal control. Shrinkage of the droplet networks prior to use achieves spatial control over gene expression with ≈50 µm resolution. Ways to store chemical signals in the droplet networks and to activate release at controlled points in time are also demonstrated. Finally, it is shown that the spatially-controlled delivery system can regulate competition between bacteria by inducing the patterned expression of toxic bacteriocins. This system provides the groundwork for the use of picoliter droplet networks in fundamental biology and in medicine in applications that require the controlled formation of chemical gradients (i.e., for the purpose of local control of gene expression) within a target group of cells.

Progress in atom visualization and miniaturization in microelectronics resulted in the discovery of nanomaterials in the second half of the 20th century [...].

A vicious cycle between microbiota dysbiosis and hyperactivated inflammation, hardly disrupted by conventional therapies, remains a significant clinical challenge for periodontitis treatment. Herein, by cloaking a cascade catalysis system in an engineered macrophage membrane, a nanodecoy-based strategy, with targeted bacteria-killing and immunomodulatory abilities, is proposed for reshaping the hostile periodontitis microenvironment. Specifically, recombinant human antimicrobial peptide, LL-37, is anchored to a Toll-like receptor-enriched macrophage membrane via genetic engineering, which facilitates the specific bacteria elimination and efficient tissue retention of the nanodecoys. Moreover, the cascade catalysis system integrates L-amino acid oxidase (LAAO) with hollowed manganese dioxide (hMnO2) by reciprocal elevation of the catalytic efficiency of hMnO2 and LAAO, leading to accelerated O2 generation under a hypoxic microenvironment and disrupted metabolism of periodontopathogenic bacteria. Notably, the nanodecoys trigger the nuclear translocation of NF-E2-related factor-2 (NRF2) to reduce oxidative stress response and rewire the polarization of macrophages, thereby boosting the osteogenic differentiation of osteoblasts. Furthermore, the alveolar bone regeneration therapeutically benefits from the nanodecoys in vivo. Altogether, these results highlight the attractive functions of engineered macrophage membrane-cloaked nanodecoys for effective periodontitis treatment.

Immunosenescence, the age-associated decline of the immune system, is pivotal in fostering drug resistance within the tumor microenvironment (TME). The accumulation of senescent immune cells and the release of pro-inflammatory senescence-associated secretory phenotype (SASP) factors create a milieu that supports tumor survival and undermines therapeutic efficacy. Traditional cancer treatments often fail to address this underlying issue, leading to suboptimal outcomes. This article proposes an innovative strategy to overcome immunosenescence-induced drug resistance through the nanoparticle-mediated delivery of herbal-derived natural products (HDNPs), which possess senolytic and immunomodulatory properties capable of clearing senescent cells and rejuvenating immune function. Nanoparticle delivery systems enhance these compounds' stability, bioavailability, and targeted delivery to the TME and senescent immune cells. By harnessing the synergistic effects of HDNPs and nanotechnology, this approach offers a novel and multifaceted solution to drug resistance in cancer therapy. It holds the potential to restore immune surveillance, reduce pro-survival signaling in cancer cells, and enhance the efficacy of conventional treatments. This paradigm shift emphasizes the importance of addressing immunosenescence as a therapeutic target and paves the way for more effective and personalized cancer interventions.

DNA nanotechnology has revolutionized materials science and biomedicine by enabling precise manipulation of matter at the nanoscale. DNA nanostructures (DNs) in particular represent a promising frontier for targeted therapeutics. Engineered DNs offer unprecedented molecular programmability, biocompatibility, and structural versatility, making them ideal candidates for advanced drug delivery, organelle regulation, and cellular function modulation. This Perspective explores the emerging role of DNs in modulating cellular behavior through organelle-targeted interventions. We highlight current advances in nuclear, mitochondrial, and lysosomal targeting, showcasing applications ranging from gene delivery to cancer therapeutics. For instance, DNs have enabled precision mitochondrial disruption in cancer cells, lysosomal pH modulation to enhance gene silencing, and nuclear delivery of gene-editing templates. While DNs hold immense promise for advancing nanomedicine, outstanding challenges include optimizing biological interactions and addressing safety concerns. This Perspective highlights the current potential of DNs for rational control of targeted organelles, which could lead to novel therapeutic strategies and advancement of precision nanomedicines in the future.

Acute lymphoblastic leukemia (ALL) is a malignant tumor caused by abnormal proliferation of B-line or T-line lymphocytes in the bone marrow. Traditional treatments have limitations. Because of their unique advantages, nanodrug delivery systems (NDDSs) show great potential in the treatment of ALL. In this paper, the pathological features of ALL, the limitations of current therapeutic methods, and the definition and composition of NDDSs were reviewed. Research strategies for the use of NDDSs in the treatment of ALL were discussed. In addition, challenges and future development directions of NDDSs in the treatment of ALL were also discussed, aiming to provide reference for the application of NDDSs in the diagnosis and treatment of ALL.

In situ vaccination (ISV) has emerged as a promising strategy in cancer immunotherapy, offering a targeted approach that uses the tumor microenvironment (TME) to stimulate an immune response directly at the tumor site. This method minimizes systemic exposure while maintaining therapeutic efficacy and enhancing safety. Recent advances in nanotechnology have enabled new approaches to ISV by utilizing nanomaterials with unique properties, including enhanced permeability, retention, and controlled drug release. ISV employing nanomaterials can induce immunogenic cell death and reverse the immunosuppressive and hypoxic TME, thereby converting a "cold" tumor into a "hot" tumor and facilitating a more robust immune response. This review examines the mechanisms through which nanomaterials-based ISV enhances anti-tumor immunity, summarizes clinical applications of these strategies, and evaluates its capacity to serve as a neoadjuvant therapy for eliminating micrometastases in early-stage cancer patients. Challenges associated with the clinical translation of nanomaterials-based ISV, including nanomaterial metabolism, optimization of treatment protocols, and integration with other therapies such as radiotherapy, chemotherapy, and photothermal therapy, are also discussed. Advances in nanotechnology and immunotherapy continue to expand the possible applications of ISV, potentially leading to improved outcomes across a broad range of cancer types.

Autophagy, a fundamental cellular process, is a sensitive indicator of environmental shifts and is crucial for the clearance of cellular debris, the remodeling of cellular architecture, and the facilitation of cell growth and development. The interplay between stromal, tumor, and immune cells within the tumor microenvironment is intricately linked to autophagy. Therefore, the modulation of autophagy in these cell types is essential for developing effective cancer treatment strategies. This review describes the design and optimization of nanomaterials that modulate autophagy in tumor-associated and immune cells. This review elucidates the primary mechanisms by which nanomaterials induce autophagy and discusses their application in cancer therapy, underscoring the potential of these materials to eradicate cancer cells, bolster the immune response, and elicit robust, enduring antitumor immunity, thereby advancing the frontiers of oncological treatment.

Cell membrane coating has emerged as a promising strategy for the surface modification of biomaterials with biological membranes, serving as a cloak that can carry more functions. The cloaked biomaterials inherit diverse intrinsic biofunctions derived from different cell sources, including enhanced biocompatibility, immunity evasion, specific targeting capacity, and immune regulation of the regenerative microenvironment. The intrinsic characteristics of biomimicry and biointerfacing have demonstrated the versatility of cell membrane coating technology on a variety of biomaterials, thus, furthering the research into a wide range of biomedical applications and clinical translation. Here, the preparation of cell membrane coatings is emphasized, and different sizes of coated biomaterials from nanoscale to macroscale as well as the engineering strategies to introduce additional biofunctions are summarized. Subsequently, the utilization of biomimetic membrane-cloaked biomaterials in biomedical applications is discussed, including drug delivery, imaging and phototherapy, cancer immunotherapy, anti-infection and detoxification, and implant modification. In conclusion, the latest advancements in clinical and preclinical studies, along with the multiple benefits of cell membrane-coated nanoparticles (NPs) in biomimetic systems, are elucidated.

Active targeting nanoparticles are a new generation of drug and gene delivery systems with the potential for greatly improved therapeutics delivery compared to conventional nanomedicine approaches. Despite their potential, the translation of active targeting nanoparticles faces challenges in production scale-up and batch consistency. Accurate quality control methods for nanoparticle therapeutic payload and coating characterization are critical for attaining the desired levels of batch repeatability, drug/gene loading efficiency, targeting molecule coating effectiveness, and safety profiles. Current limitations in nanoparticle characterization technologies, such as relying on ensemble-average analysis, pose challenges in assessing the drug/gene content and surface modification heterogeneity, which can greatly affect therapeutic outcomes. Single-molecule analysis technologies have emerged as a promising alternative, offering rich information on heterogeneity and stochastic variations between nanoparticle batches. This review first evaluates and identifies the challenges of traditional nanoparticle characterization tools that rely on indirect, bulk solution quantification methods. Subsequently, newly emerging characterization technologies are introduced for the quantification of therapeutic loading and targeted moiety coating efficiencies with single-nanoparticle resolution, to help guide researchers towards advancing the translation of active targeting nanoparticles into the clinical setting.

Polymeric nanoparticles represent an innovative approach to drug delivery, particularly for addressing complex diseases like cancer. Their nanoscale dimensions facilitate targeted cellular uptake and effective navigation of biological barriers. With a broad range of polymerisation and functionalisation techniques, these nanoparticles can enable precise drug release, enhanced stability, and improved bioavailability while minimising side effects. Compared to conventional carriers, polymeric nanoparticles offer superior stability and versatility. However, despite these beneficial attributes, challenges remain in understanding their dynamic behaviour and interactions within biological systems. This mini-review aims to highlight key characterisation methods for studying polymeric nanocarriers, explore recent advances, and examine current challenges that must be addressed to optimise their therapeutic potential and advance these promising targeted drug delivery systems.

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, characterized by rapid growth, invasive infiltration into surrounding brain tissue, and resistance to conventional therapies. Despite advancements in surgery, radiotherapy, and chemotherapy, median survival remains approximately 15 months, underscoring the urgent need for innovative treatments. Key considerations informing treatment development include oncogenic genetic and epigenetic alterations that may dually serve as therapeutic targets and facilitate treatment resistance. Various immunotherapeutic strategies have been explored and continue to be refined for their anti-tumor potential. Technical aspects of drug delivery and blood-brain barrier (BBB) penetration have been addressed through novel vehicles and techniques including the incorporation of nanotechnology. Molecular profiling has emerged as an important tool to individualize treatment where applicable, and to identify patient populations with the most drug sensitivity. The goal of this review is to describe the spectrum of potential GBM therapeutic targets, and to provide an overview of key trial outcomes. Altogether, the progress of clinical and preclinical work must be critically evaluated in order to develop therapies for GBM with the strongest therapeutic efficacy.

Self-assembly prodrugs usually consist of drug modules, activation modules, and assembly modules. The selection of suitable modules to construct prodrug nanoassemblies with self-assembly stability and "intelligent" activation is a challenge. As a common assembly module, oleic acid can provide a driving force and steric hindrance for prodrugs self-assembly. However, the unsaturated double bond of oleic acid is readily oxidized and it affects its chemical stability. Herein, two docetaxel (DTX) prodrugs were designed using disulfide bonds as activation modules and two different fatty acids (isostearic acid and oleic acid) as assembly modules, respectively. Compared with oleic acid, isostearic acid had higher chemical stability. Simultaneously, the terminal propyl structure of isostearic acid compensated for the steric hindrance without a double bond. Overall, this structural deformation improved the self-assembly ability and chemical stability of the prodrug nanoassemblies, thus balancing the effectiveness and safety of the prodrugs. Our findings reveal the importance of the assembly modules and provide a guidance for the rational design of prodrug nanoassemblies.

This study pioneers a pH-responsive core-shell nanoplatform integrating magnetic Fe3O4-hydroxyapatite (Fe/HAP) with polysuccinimide (PSI) polymer, engineered to enhance tumor-targeted delivery of fluorouracil (5-FU) for liver cancer therapy.

The individual components-hydroxyapatite (HAP), magnetite (F3O4), iron-doped hydroxyapatite (Fe/HAP), and polysuccinimide (PSI)-were synthesized and systematically characterized through Fourier-transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). Through a combination of single-factor experiments and Box-Behnken design (BBD) response surface methodology, the formulation parameters were optimized for two nanoparticle systems: (1) non-magnetic 5-FU-loaded PSI-HAP (designated as 5-FU@DC, where DC denotes "drug carrier") and (2) magnetic-targeted formulations 5-FU@PSI-Fe/HAP with varying iron content (5-FU@FeDC20, 5-FU@FeDC30, 5-FU@FeDC40). The engineered nanoparticles were thoroughly characterized for their morphological characteristics, hydrodynamic properties (particle size distribution and zeta potential), magnetic responsiveness (vibrating sample magnetometry), and pH-dependent drug release profiles. Nile Red was used to label the drug-loaded nanoparticles, and small animal imaging technology was employed to track their distribution in mice in vivo. Furthermore, in vitro studies examined the effects of these formulations on the proliferation, apoptosis, and migration of Huh-7 liver cancer cells.

The formulations (5-FU@DC and 5-FU@FeDC) were found to form uniform spherical or near-spherical nanoparticles. Vibrating sample magnetometer (VSM) analysis confirmed that the 5-FU@FeDC formulations displayed paramagnetic properties. Zeta potential measurements showed that all prepared systems had negative charges, similar to human biological membranes. All nanoparticles gradually released the drug at pH levels above 5, with the release rate increasing as the pH increased. Compared to the non-magnetic 5-FU@DC formulation, the magnetic 5-FU@FeDC formulations showed significantly longer distribution and retention times in liver tissue and more effectively inhibited the proliferation of Huh-7 cells.

The current study developed a magnetic targeting nano-delivery system using PSI and Fe/HAP as formulation excipients. The system offers uniform particle size, a simple preparation process, and a cost-effective method for targeted drug delivery. It is not only suitable for liver-targeted drug delivery but also applicable for drug delivery to other tissues in the body for anti-tumor drugs.

Nanotechnology-based drug delivery systems have improved target medicines' therapeutic efficacy and specificity in cancer therapy. Imatinib, one of the tyrosine kinase inhibitors widely used for treating chronic myeloid leukemia and gastrointestinal stromal tumors (GIST), faces many drawbacks, such as poor solubility, reduced bioavailability, and the development of resistance. The paper critically reviews advances in nanotechnology-based approaches toward the delivery of Imatinib, relating to polymeric, lipid-based, carbon-based, and stimuli-responsive nanoparticles. These methods enhance solubility, stability, and targeted distribution and are often used to facilitate the co-delivery of other anticancer drugs with considerable problems in cancer treatment. Although much potential for these technologies exists, scalability, safety, and regulatory approval, among other features, need resolution before real cost can meet clinical efficacy. Further directions would go toward bio-inspired system development, enhancing regulatory frameworks, and cost-effective manufacturing processes that bring nanotechnology into the realm of standard treatment for cancer.

Synthetic biology and nanotechnology fusion represent a transformative approach promoting fundamental and clinical biomedical science development. In SynBioNanoDesign, biological systems are reimagined as dynamic and programmable materials to yield engineered nanomaterials with emerging and specific functionalities. This review elucidates a comprehensive examination of synthetic biology's pivotal role in advancing engineered nanomaterials for targeted drug delivery systems. It begins with exploring the fundamental synergy between synthetic biology and nanotechnology, then highlights the current landscape of nanomaterials in targeted drug delivery applications. Subsequently, the review discusses the design of novel nanomaterials informed by biological principles, focusing on expounding the synthetic biology tools and the potential for developing advanced nanomaterials. Afterward, the research advances of innovative materials design through synthetic biology were systematically summarized, emphasizing the integration of genetic circuitry to program nanomaterial responses. Furthermore, the challenges, current weaknesses and opportunities, prospective directions, and ethical and societal implications of SynBioNanoDesign in drug delivery are elucidated. Finally, the review summarizes the transformative impact that synthetic biology may have on drug-delivery technologies in the future.

Schistosomiasis is a neglected tropical disease caused by Schistosoma sp., and praziquantel (PZQ) is the first-line treatment. However, traditional PZQ formulations have low solubility and fast metabolism, limiting its effectiveness. Thus, nanoparticles have been proposed to improve the bioavailability and efficacy of poorly soluble antischistosomal drugs.

This systematic review used in vivo preclinical studies to map the available evidence and compare the efficacy of free PZQ and PZQ-based nanostructured formulations (N-PZQ) for schistosomiasis treatment.

PubMed, Embase, Scopus, and Web of Science were searched, and 1186 experimental studies published between 1974 and 2024 were screened. Parasitological, histopathological, pharmacokinetic, and toxicological outcomes were evaluated.

Twelve relevant studies were identified exploring N-PZQ formulations based on liposomes, nanoliposomes, and nanocrystals. N-PZQ demonstrated better therapeutic efficacy than free PZQ, reducing parasite load, modifying oogram profiles, and down-regulating liver granuloma development (number and size). N-PZQ also exhibited improved pharmacokinetic profile, with enhanced bioavailability and longer half-life, as well as reduced toxicity (cytotoxicity, genotoxicity, and hepatotoxicity) compared to free PZQ.

PZQ-based nanostructured formulations represent a promising strategy to enhance schistosomiasis treatment by improving chemotherapy efficacy, optimizing antiparasitic responses, pharmacokinetics, and reducing drug toxicity.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease. UC treatments are limited by significant adverse effects associated with non-specific drug delivery, such as systematic inhibition of the host immune system. Endoscopic delivery of a synthetic hydrogel material with biocompatible gelation that can efficiently cover irregular tissue surfaces provides an effective approach for targeted drug delivery at the gastrointestinal (GI) tract. An ideal integration of synthetic material with intestinal epithelium entails an integrated and preferable chemically bonded interface between the hydrogel and mucosal surface. In this study, a photo-triggered coupling reaction is leveraged as the crosslinking platform to develop a mucosal-adhesive hydrogel, which is compatible with endoscope-directed drug delivery for UC treatment. The results demonstrated superior spatiotemporal specificity and drug pharmacokinetics with this delivery system in vivo. Delivery of different drugs with the hydrogel leads to greatly enhanced therapeutic efficacy and significantly reduced systemic drug exposure with rat colitis models. The study presents a strategy for targeted and persistent drug delivery for UC treatment.

Molecular imprinting technology (MIT), a synthetic strategy to create tailor-made molecular specificity, has recently achieved significant advancements. Epitope imprinting strategy, an improved MIT by imprinting the epitopes of biomolecules (e.g., proteins and nucleic acids), enables to target the entire molecule through recognizing partial epitopes exposed on it, greatly expanding the applicability and simplifying synthesis process of molecularly imprinted polymers (MIPs). Thus, epitope imprinting strategy offers promising solutions for the fabrication of smart biomaterials with molecular targeting and exhibits wide applications in various biomedical scenarios. This review explores the latest advances in epitope imprinting techniques, emphasizing selection of epitopes and functional monomers. We highlight the significant improvements in specificity, sensitivity, and stability of these materials, which have facilitated their use in bioanalysis, clinical therapy, and pharmaceutical development. Additionally, we discuss the application of epitope-imprinted materials in the recognition and detection of peptides, proteins, and cells. Despite these advancements, challenges such as template complexity, imprinting efficiency, and scalability remain. This review addresses these issues and proposes potential directions for future research to overcome these barriers, thereby enhancing the efficacy and practicality of epitope molecularly imprinting technology in biomedical fields.