Tannic acid-based nanoplatforms represent a promising approach to overcome current challenges in anticancer drug delivery by enhancing therapeutic efficacy, reducing systemic toxicity, and improving tumor targeting. In this study, we developed a novel nanoparticle system-tannic acid-condensed lipid nanoparticles (TLNPs) through the self-assembly of tannic acid (TA), DSPE-PEG2k, and doxorubicin (DOX). The resulting nanoparticles DOX@TLNPs exhibited a uniform size, satisfactory encapsulation efficiency, excellent stability, and sustained drug release properties. In vitro evaluations demonstrated efficient cellular uptake and comparable cytotoxic activity to free DOX against multiple breast cancer cell lines (SKBR3, MCF-7). In vivo evaluation involved positron emission tomography (PET) imaging of 89Zr-labeled DOX@TLNPs administered to SKBR3 tumor-bearing mice. The nanoparticles showed prolonged circulation and enhanced tumor accumulation, evidenced by a significantly higher area under the curve compared to free DOX, likely due to the enhanced permeability and retention effect. Furthermore, antitumor studies revealed that DOX@TLNPs markedly inhibited tumor growth, improved survival rates, and induced increased apoptosis alongside reduced proliferation within tumor tissues, without eliciting significant histopathological changes in major organs. These findings highlight the significant potential of TA-condensed TLNPs as a safe, robust, and effective nanomedicine platform for targeted cancer treatment.

Gastric cancer presents a significant global health concern, with conventional therapies often limited in effectiveness. The abnormal redox balance in gastric cancer cells may represent a breakthrough in the treatment of gastric cancer. In this study, we report for the first time the development of reactive oxygen species (ROS)-sensitive hetero-polymeric prodrug nanoparticles (NPs) designed for the co-delivery of the Chinese herbal extract oridonin (ORI) and dihydroartemisinin (DHA) in combination therapy for gastric cancer. This strategy aims to disrupt the intracellular redox balance and ultimately induce ferroptosis in gastric cancer cells. The ROS-responsive ORI and DHA polymeric prodrug were synthesised by conjugating ORI or DHA to poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLL) via a ROS-sensitive linker thioketal (TK). The resulting polymeric prodrugs self-assemble in water to form NPs OD-M. After internalization by gastric cancer cells, OD-M released ORI and DHA in response to high ROS conditions within cancer cells. The released ORI reacts with GSH to induce GSH depletion while DHA amplifies intracellular ROS levels, ultimately inducing ferroptosis in gastric cancer cells. Experimental results demonstrate that OD-M acts as both a GSH scavenger and ROS generator, effectively disrupting intracellular redox balance, inducing ferroptosis, and exhibiting effective anticancer efficacy in vitro and in vivo, offering a departure from traditional methods.

Humans are home to a diverse community of bacteria, many of which form symbiotic relationships with their host. Notably, tumors can also harbor their own unique bacterial populations that can influence tumor growth and progression. These bacteria, which selectively colonize hypoxic and acidic tumor microenvironments, present a novel therapeutic strategy to combat cancer. Advancements in synthetic biology enable us to safely and efficiently program therapeutic drug production in bacteria, further enhancing their potential. This review provides a comprehensive guide to utilizing bacteria for cancer treatment. We discuss key considerations for selecting bacterial strains, emphasizing their colonization efficiency, the delicate balance between safety and anti-tumor efficacy, and the availability of tools for genetic engineering. We also delve into strategies for precise spatiotemporal control of drug delivery to minimize adverse effects and maximize therapeutic impact, exploring recent examples of engineered bacteria designed to combat tumors. Finally, we address the underlying challenges and future prospects of bacterial cancer therapy. This review underscores the versatility of bacterial therapies and outlines strategies to fully harness their potential in the fight against cancer.

Lipid metabolism has been increasingly recognized to play an influencing role in tumor initiation, progression, metastasis, and therapeutic drug resistance. Targeting lipid metabolic reprogramming represents a promising therapeutic strategy. Despite their structural complexity and poor targeting efficacy, lipid-metabolizing drugs, either used alone or in combination with chemotherapeutic agents, have been employed in clinical practice. The advent of nanotechnology offers new approaches to enhancing therapeutic effects, includingthe targeted delivery and integration of lipid metabolic reprogramming with chemotherapy, photodynamic therapy (PDT), and immunotherapy. The integrated nanoformulation, nanomedicine, could significantly advance the field of lipid metabolism therapy. In this review, we will briefly introduce the concept of cancer lipid metabolism reprogramming, then elaborate the latest advances in engineered nanomedicine for targeting lipid metabolism during cancer treatment, and finally provide our insights into future perspectives of nanomedicine for interference with lipid metabolism in the tumor microenvironment.

Ovarian malignancies overexpress estrogen receptors (ERs), offering a therapeutic avenue for targeted drug delivery. Here, we developed a novel ER-targeted PEGylated liposome (ES-SSL-PTX/CDDP) coencapsulating paclitaxel (PTX) and cisplatin (CDDP) to enhance therapeutic efficacy and mitigate systemic toxicity. ES-SSL-PTX/CDDP exhibited a spherical shape with a hydrodynamic diameter of around 150 nm, a negative zeta potential of about -20 mV, and high encapsulation efficiencies of 83.7% for PTX and 41.1% for CDDP. ES-SSL-PTX/CDDP showed a sustained release pattern, with release rates of <60% for both drugs within 12 h. Meanwhile, ES-SSL-PTX/CDDP demonstrated excellent storage and serum stability, with the leakage rates less than 30% when stored at either 4 or 25 °C. ES-SSL-PTX/CDDP exhibited a strong antitumor effect in athymic mice with the tumor volume 8.50 times smaller than that in the control group on the 27th day, and the tumor inhibition rate reached 87.3%. Pharmacokinetic studies revealed prolonged circulation of ES-SSL-PTX/CDDP, with elimination half-lives (t1/2β) of 13.84 h (PTX) and 7.18 h (CDDP), which were 8.82- and 1.83-fold higher than those of PTX/CDDP, and clearance rates reduced to 0.01 L/h/kg (PTX) and 0.02 L/h/kg (CDDP), being 18.0- and 4.0-fold lower than those of PTX/CDDP. Acute toxicity results demonstrated a 2.12-fold increase in the LD50 of ES-SSL-PTX/CDDP (27.82 mg/kg for PTX; 19.87 mg/kg for CDDP) versus PTX/CDDP. Long-term toxicity studies demonstrated that ES-SSL-PTX/CDDP attenuated myelosuppression and nephrotoxicity, with no histopathological abnormalities observed across 32 tissues after 16 weeks of administration. This study highlights the potential of ES-SSL-PTX/CDDP to improve the efficacy and reduce the toxicity of platinum-taxane regimens in the treatment of ovarian cancer.

Photodynamic therapy (PDT) is widely utilized in cancer treatment as a noninvasive strategy. Phycocyanin (PC), a natural water-soluble photosensitizer with nontoxic properties, shows promise as a PDT candidate. However, the limitations of PC when used alone in PDT for cancer treatment, such as inadequate tumor delivery and weak efficacy, must be addressed. Herein, an efficient theranostic manganese (Mn)-based PC nanocomplex (PC@Mn) was synthesized through a straightforward one-pot self-assembly reaction for synergistic antitumor therapy. The PC@Mn nanoparticles were found to have a suitable size (∼129 nm) and demonstrated excellent biocompatibility and biosafety. Importantly, these nanoparticles exhibited enhanced biodistribution with improved tumor targeting and retention properties. When combined with 650 nm laser irradiation, PC@Mn showed a significant enhancement in the PDT effect in vivo. Additionally, PC@Mn displayed promising magnetic resonance (MR) imaging capabilities, with a high relaxation rate (r1 = 10.14 mM-1 s-1) and an extended imaging time window (4 h). This feature enables real-time monitoring of the nanoparticles' distribution within tumors, facilitating precise determination of the optimal PDT treatment time. Overall, the study highlights PC@Mn as a simple, safe, and highly efficient strategy for synergistic antitumor therapy. Its ability to combine PDT with MR imaging for real-time guidance represents an efficient approach to cancer treatment, promising improved therapeutic outcomes and potential clinical applications in the future.

Natural products, derived from plants, animals, and microorganisms, offer a wide range of pharmacological activities, including anti-infective, antifungal, anti-tumor, cholesterol-lowering, and anti-inflammatory effects. However, their clinical use is often limited by challenges such as low stability, poor bioavailability, and short half-lives. Thus, developing effective drug delivery systems for these compounds is crucial.

This review highlights the integration of natural products with nano-drug delivery systems, focusing on recent advancements that utilize the enhanced permeability and retention (EPR) effect to improve their stability, bioavailability, and targeting. By embedding natural compounds into polymeric nanoparticles or similar nanoplatforms, these formulations significantly enhance pharmacokinetic and pharmacodynamic properties, overcoming traditional limitations.

Combining natural products with nanoparticle technology shows great potential to expand their therapeutic applications. Although these innovations improve the pharmacological profiles of natural compounds, continued research is essential to optimize clinical use. Advances in nanoparticle design and delivery strategies will be key to maximizing the therapeutic potential of natural products, addressing existing challenges, and enhancing their efficacy in disease treatment.

Mitochondrial reactive oxygen species (mROS) are generated as byproducts of mitochondrial oxidative phosphorylation. Changes in mROS levels are involved in tumorigenesis through their effects on cancer genome instability, sustained cancer cell survival, metabolic reprogramming, and tumor metastasis. Recent advances in nanotechnology offer a promising approach for precise regulation of mROS by either enhancing or depleting mROS generation. This review examines the association between dysregulated mROS levels and key cancer hallmarks. We also discuss the potential applications of mROS-targeted nanoparticles that artificially manipulate ROS levels in the mitochondria to achieve precise delivery of antitumor drugs.

Surgery remains the gold standard in the management of head and neck squamous cell carcinoma (HNSCC). However, the anatomical complexity of these cancers, combined with the difficulty in discriminating between healthy and cancerous tissue and the detection of microlesions, complicates tumor resection, resulting in positive surgical margins, which are associated with a poor patient prognosis. Fluorescence-guided surgery (FGS) has emerged as a promising technique in the management of HNSCC, improving tumor resection and margin assessment. FGS strategies can be roughly divided into three approaches; namely, natural tissue autofluorescence, passive delivery of fluorescent contrast agents, and active targeting. This review provides a comprehensive overview of the advances made in FGS of head and neck cancers, particularly aiming to improve surgical margin assessment. Recently, the field has shown promising results by addressing contrast agents targeted to the overexpressed epidermal growth factor receptor (EGFR), both in preclinical and clinical settings. The identification of new targets such as αVβ6 integrin, uPAR, PARP1, and so on, as well as the development of contrast agents, are key steps in the further development of FGS of head and neck cancers, making it an essential tool in precision oncology. Among these, as was demonstrated in preclinical studies, the αVβ6 integrin is emerging as a promising target due to its high and specific expression in tumor and tumor margins.

Oxygen-less dependent Type I photosensitizers (PSs) have emerged as a crucial strategy for enhancing photodynamic therapy efficiency in treating hypoxic tumors. However, solid tumors have normoxia regions situated near functional blood vessels and hypoxia regions in their interiors. To maximize the utilization of oxygen within solid tumors, herein a viable donor optimizing approach is developed to enhance both Type I&II reactive oxygen species generation of PSs. At the same mole concentration, one optimized PS (named DE) generated 9 times more 1O2 than commercial Type II PS Chlorin e6 upon white light irradiation for 60 s. Compared to the commercial Type I PS Rose Bengal, •OH generation by DE is 2.9 times more under the hypoxia condition. With its optimized Type I&II pathway under normoxia and hypoxia conditions, DE is proven to be an efficient PS for solid tumor treatment, offering a promising approach for PS development.

Liver cancer, notably hepatocellular carcinoma (HCC), poses a significant global health burden due to its high fatality rates. Conventional antitumor medications face challenges, including poor targeting, high toxicity, and drug resistance, leading to suboptimal clinical outcomes. This review focused on nanoparticle use in diagnosing and delivering medication for HCC, aiming to advance the development of nanomedicines for improved treatment outcomes. As an emerging frontier science and technology, nanotechnology has shown great potential, especially in precision medicine and personalized treatment. The success of nanosystems is attributable to their smaller size, biocompatibility, selective tumor accumulation, and lower toxicity. Nanoparticles, as a central part of nanotechnology innovation, have emerged in the field of medical diagnostics and therapeutics to overcome the various limitations of conventional chemotherapy, thus offering promising applications for improved selectivity, earlier and more precise diagnosis of cancers, personalized treatment, and overcoming drug resistance. Nanoparticles play a crucial role in drug delivery and imaging of HCC, with the body acting as a delivery system to target and deliver drugs or diagnostic reagents to specific organs or tissues, helping to accurately diagnose and target therapies while minimizing damage to healthy tissues. They protect drugs from early degradation and increase their biological half-life.

Cancer-associated fibroblasts (CAFs) are key drivers of hepatocellular carcinoma (HCC) through their promotion of fibrosis and immune suppression activity. To overcome this stroma-immune barrier, we developed D/F@MRL, a stroma-immune co-targeting nanoplatform that enables the spatiotemporal coordination of CAF reprogramming and immune activation. In D/F@MRL, MMP-2-responsive hybrid liposomes (MRL) was employed to co-load digoxin (Dig) and PD-L1-degrading nanofibers (NFs). Upon encountering the MMP-2-enriched HCC stroma, D/F@MRL undergoes enzymatic cleavage, thereby enabling the targeted release of Dig and NFs within the HCC microenvironment. Mechanistically, Dig inhibits the phosphorylation of SMAD3 in CAFs, while PD-L1 degradation destabilizes the TGFβ receptor, synergistically silencing TGF-β/Smad signaling to reprogram CAFs. This combination not only disrupts the fibrotic barrier but also creates a feed-forward loop that further enhances drug penetration, while reinforcing the immune activation driven by Dig-induced immunogenic cell death (ICD) and PD-L1 degradation. In the humanized immune PDX model, D/F@MRL successfully reprogrammed CAFs and robustly remodeled the stromal and immune microenvironments without causing systemic toxicity, highlighting its promising potential for clinical translation. By integrating CAF reprogramming with ICD and immune checkpoint inhibition, this strategy overcame the limitations of single-target therapies, induced robust immune activation, further provided a clinic-transformative approach for fibrotic malignancies.

Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide. Transcatheter arterial chemoembolization has become a common treatment modality for some patients with unresectable advanced HCC. Since the introduction of nanomaterials in 1974, their use in various fields has evolved rapidly. In medical applications, nanomaterials can serve as carriers for the delivery of chemotherapeutic drugs to tumour tissues. Additionally, nanomaterials have potential for in vivo tumour imaging. This article covers the properties and uses of several kinds of nanomaterials, focusing on their use in transcatheter arterial chemoembolization for HCC treatment. This paper also discusses the limitations currently associated with the use of nanomaterials.

Sorafenib (Sor), recognized as a frontline multi-kinase inhibitor, constitutes the primary targeted therapy for hepatocellular carcinoma (HCC). Despite its potential, many HCC patients exhibit reduced responsiveness to Sor, thereby undermining its therapeutic efficacy. Recent studies highlight the importance of nuclear factor erythroid-2-related factor 2 (Nrf2) activation in HCC, which contributes to Sor resistance. Brusatol (Bru), a plant-derived Nrf2 inhibitor, counteracts this resistance but faces challenges due to its poor solubility in aqueous media. In this study, we developed a glutathione (GSH)-responsive nanoplatform that effectively dispersed in water for the co-delivery of Bru and Sor (B/S NP). This approach enhanced Bru's therapeutic efficacy and increased Sor sensitivity in HCC. Our nanoplatform significantly reduced Nrf2 expression, thereby increasing Sor sensitivity both in vitro and in vivo, while presenting a favorable biosafety profile. These findings suggest that the nanoplatform-mediated co-delivery of Bru and Sor offers an innovative approach to enhance Sor's effectiveness in HCC treatment.

Delivery of nanoparticles (NPs) to solid tumors has long relied on enhanced permeability and retention (EPR) effect, involving permeation of NPs through a leaky vasculature with prolonged retention by reduced lymphatic drainage in tumor. Recent research studies and clinical data challenge EPR concept, revealing alternative pathways and approaches of NP delivery. The area was significantly impacted by the implementation of intravital optical microscopy, unraveling delivery mechanisms at cellular level in vivo. This review presents analysis of the reasons for EPR heterogeneity in tumors and describes non-EPR based concepts for drug delivery, which can supplement the current paradigm. One of the approaches is targeting tumor endothelium by NPs with subsequent intravascular drug release and gradient-driven drug transport to tumor interstitium. Others exploit various immune cells for tumor infiltration and breaking endothelial barriers. Finally, we discuss the involvement of active transcytosis through endothelial cells in NP delivery. This review aims to inspire further understanding of the process of NP extravasation in tumors and provide insights for developing next-generation nanomedicines with improved delivery.

Gambogic acid(GA)is a natural compound that exhibits strong antitumor activity against a variety of tumors. However, its poor water solubility, low specificity, and high toxicity lead to inevitable systemic adverse effects. To minimize side effects, combining gambogic acid (GA) with delivery systems such as nanohydrogels to develop an in situ vaccine system (ISV) shows great promise. In this study, we loaded GA into a novel in situ nanocomposite hydrogel vaccine system (Gel-NPs@GA) along with a near-infrared (NIR) fluorescent dye, IR-1061. The Gel-NPs@GA system allowed for temperature-triggered gelation, simplifying injection and the in vivo formation of a drug-releasing gel, with near-infrared monitoring for drug metabolism. Slow, continuous release of gelatinase-targeted GA nanoparticles from the hydrogel occurs, followed by cleavage of mPEG-peptide-PCL conjugates by gelatinase, causing particle aggregation for endocytosis by tumor cells. This approach tackled solubility issues and curbs excessive GA release, boosting therapeutic drug levels. The sustained GA release induces tumor cell apoptosis, releasing tumor antigens and reprogramming the immune-suppressive tumor microenvironment. In the CT26 colorectal cancer mice model, this in situ vaccine system significantly inhibited tumor growth. By integrating information about immune cell clusters within the tumor microenvironment with RNA sequencing results, we hypothesized that Gel-NPs@GA could synergistically stimulate the immune response through various pathways, promote the maturation of dendritic cells (DCs), increase the infiltration of T cells, and thereby remodel the tumor's immune microenvironment.

5-Fluorouracil (5-FU) is commonly used as a chemotherapeutic drug for advanced HCC. However, the effectiveness of 5-FU is limited by the emergence of resistance and poor targeting efficiency. Combining 5-FU with natural compounds has shown promise in HCC treatment. In this study, we prepared carrier-free nanoparticles (GEN-Cu-GEN@FUA) containing 5-FU and genistein (GEN) in a synergistic ratio via a green synthesis procedure. The resulting GEN-Cu-GEN@FUA nanoparticles had a spherical or near spherical shape, a dynamic size of 129.3 ± 40.1 nm, and a high drug loading content of approximately 21.40% (5-FU) and 61.48% (GEN). These nanoparticles exhibited approximately 3.6-fold lower IC50 value than 5-FU alone in Bel-7402 cells and resulted in a 3.7-fold greater reduction in tumor weight compared to 5-FU alone in Bel-7402 tumor-bearing BALB/c mice. Importantly, the nanoparticles showed negligible systemic toxicity due to their synergistic effect on cancer cell dysfunction and significant amplification of intracellular glutathione consumption. Our findings suggest that the developed carrier-free nanomedicines offer a highly promising platform for the co-delivery of genistein (GEN) copper(II) complexes and 5-FU, with easy fabrication and great potential for clinical translation in HCC synergistic therapy.

Background/Objective: Breast cancer remains the most common malignancy among women worldwide, contributing to high morbidity and mortality rates. Many anti-cancer drugs have been derived from medicinal plants, and frankincense from Boswellia carterii is notable for its anti-inflammatory, anti-neoplastic, and anti-carcinogenic properties. Using gas chromatography/mass spectrometry (GC/MS), 48 components were identified in B. carterii essential oil, and the major constituent was α-pinene (35.81%). Method: In this study, we investigated the anti-tumor effects of frankincense essential oil (FEO) and its nano-formulation with chitosan (FEO-CSNPs) using in vitro breast cancer models (MCF-7, MDA-MB-231, and 4T1 cells) and in vivo mouse mammary carcinoma (4T1) models (Balb/c). Results: The results showed significant reductions in cell viability. At 10 μg/mL, the FEO showed the highest reduction in the C-166 cells, while at 100 μg/mL, the FEO exhibited a stronger cytotoxicity in the MDA-MB-231 and 4T1 cells compared to the FEO-CSNPs and CSNPs. The FEO-CSNPs exhibited cell growth arrest in the S, G2/M, and G1/S phases in the MCF-7, MDA-MB-231, and 4T1 cell lines (36.91%, 23.12%, and 33.58%), in addition to increased apoptosis rates in the MCF-7, MDA-MB-231, and 4T1 cell lines (33.04%, 36.39%, and 42.19%). The wound healing assays revealed a decreased migratory ability in the treated cells. The in vivo experiments in the balb/c mice demonstrated a reduction in the tumor volume, with a histopathological analysis confirming extensive tumor necrosis. Moreover, the FEO and FEO-CSNPs showed notable antioxidant and arginase activity. The gene expression analysis via qPCR indicated the upregulation of tumor suppressor genes and the downregulation of oncogenes. Conclusions: These findings suggest that FEO and its nano-formulation, particularly in the form of FEO-CSNPs as an oral formulation, display enhanced efficacy, warranting further preclinical and clinical research to develop innovative treatment strategies.

Immune checkpoint blockade therapy using programmed cell death 1 (PD1) or programmed death ligand 1 (PD-L1) has made significant progress in the treatment of advanced cancers, with some patients achieving long-term remission without clinical recurrence. However, only a minority of colon cancer patients respond to the therapy. Here, we report a protease-cleavable anti-PD-L1 antibody liposome, eLipo anti-PD-L1, for enhancing colon cancer therapy. In vivo, eLipo anti-PD-L1 is cleaved by legumain at colon cancer site into pegylated anti-PD-L1 and cancer-homing doxorubicin liposome. Functional assessments show cancer-targeting, legumain-responding, tumor-penetrating, and immune-activating effects, as well as efficacy in treating colon cancer-bearing mice in vivo. Further mechanistic analysis implicates genes related to T cell differentiation and T cell receptor signaling as potential molecular mediators. Lastly, human colorectal cancer tissue evaluations verify expressions of PD-L1 and legumain, hinting a potential translatability. Our study thus suggests that eLipo anti-PD-L1 may be a feasible vector for co-delivery of immunochemotherapy for colon cancer.

X-ray-excited photodynamic therapy (X-PDT), a novel synergistic therapy combining radiotherapy (RT) with photodynamic therapy (PDT), demonstrates not only more effective therapeutic outcomes but also overcomes the limitation of PDT's shallow penetration depth. Persistent luminescence nanoparticles (PLNPs) have been employed in X-PDT due to their unique afterglow emission, which yields more light to achieve more effective PDT outcomes using the same irradiation dose. However, at present, persistent luminescent materials used in X-PDT are mainly bulk crystals characterized by a nonuniform size and morphology, which are not suitable for biomedical applications, and the presence of excessive surface defects reduces the luminescence efficiency and the persistent luminescence duration. Herein, the NaYF4:Tb@NaYF4 core-shell nanoparticles with enhanced luminescence and afterglow performance and uniform morphology were prepared via the optimized solvothermal method. Their X-ray excitation optical luminescence (XEOL) and persistent luminescence (XEPL) intensities were enhanced more than 5.2 times and 3.5 times, respectively. The PLNPs were modified with a water-soluble AEP ligand and piggybacked with the photosensitizer Rose Bengal (RB) to construct an efficient X-PDT nanocoupling system. To fully utilize the afterglow of PLNPs, a unique hyperfractionated irradiation plan was designed, and the ROS yield was increased by nearly 50% at the same irradiation dose. In vivo therapeutic efficacy validation using the B16-F10-bearing C57 mouse model demonstrated that hyperfractionated irradiation combined with PLNPs showed significant therapeutic advantages. At a total dose of 2 Gy, the tumor inhibition rate was enhanced from 67.5% to 85% compared to the conventional irradiation strategy. Pathological analysis showed no significant histological damage in major organs, attesting to its negligible side effects. This study offers a novel modality, with both nanoparticles and irradiation strategy improvement, to further improve the X-PDT therapeutic efficacy and reduce side effects.

Nanobiotechnology is transforming personalized medicine by leveraging the unique properties of nanomaterials to address key challenges in targeted drug delivery, regenerative medicine, and diagnostics. The development of nanocarriers, such as liposomes, polymeric nanoparticles, dendrimers, and metallic nanoparticles, has enabled precise drug delivery with enhanced bioavailability and reduced systemic toxicity. Concurrently, nanostructured scaffolds have advanced regenerative medicine by supporting stem cell differentiation, modulating cellular microenvironments, and enhancing tissue repair. These nanoscale innovations have also led to highly sensitive biosensors and imaging agents, significantly improving early disease detection and biomarker monitoring. Despite these advancements, challenges persist, including nanoparticle-induced cytotoxicity, immunogenicity, scalability issues, and regulatory hurdles requiring extensive evaluation of long-term biocompatibility and pharmacokinetics. Addressing these limitations, recent breakthroughs in AI-assisted nanotechnology and CRISPR-Cas9-mediated gene editing are driving next-generation precision medicine, integrating nanoscale therapeutics with computational approaches to enhance efficacy. Future directions focus on nanorobotics, bioengineered nanovaccines, and theranostic platforms capable of simultaneous diagnosis and treatment, paving the way for real-time, patient-specific interventions. The successful translation of nanomedicine into clinical practice will require interdisciplinary collaboration across nanoscience, bioengineering, and translational medicine to refine nanoparticle functionalization, optimize safety profiles, and ensure equitable access to nanotherapeutics. This review provides a comprehensive overview of these advancements, challenges, and emerging opportunities in nanobiotechnology-driven precision medicine.

Preclinical studies on liposomal interleukin (IL) therapy demonstrate considerable promise in cancer treatment. This review explores the achievements, challenges, and future potential of liposomal IL encapsulation, focusing on preclinical studies.

A structured search was conducted using the PubMed and Web of Science databases with the following search terms and Boolean operators: ("liposomal interleukin" OR "liposome-encapsulated interleukin") AND ("gene therapy" OR "gene delivery") AND ("cancer" OR "tumor" OR "oncology") AND ("pre-clinical studies" OR "animal models" OR "in vitro studies".

Liposomal IL-2 formulations are notable for enhancing delivery and retention at tumor sites. Recombinant human interleukin (rhIL-2) adsorbed onto small liposomes (35-50 nm) substantially reduces metastases in murine models. Hepatic metastasis models demonstrate superior efficacy of liposomal IL-2 over free IL-2 by enhancing immune responses, particularly in the liver. Localized delivery strategies, including nebulized liposomal IL-2 in canine pulmonary metastases and intrathoracic administration in murine sarcoma models, reduce systemic toxicity while promoting immune activation and tumor regression. Liposomal IL gene therapy, delivering cytokine genes directly to tumor sites, represents a notable advancement. Combining IL-2 gene therapy with other cytokines, including IL-6 or double-stranded RNA adjuvants, synergistically enhances macrophage and T-cell activation. Liposomal IL-4, IL-6, and IL-21 therapies show potential across various tumor types. Pairing liposomal IL-2 with chemotherapy or immune agents improves remission and survival. Innovative strategies, including PEGylation and ligand-targeted systems, optimize delivery, release, and therapeutic outcomes.

Utilizing immune-stimulatory ILs through advanced liposomal delivery and gene therapy establishes a strong foundation for advancing cancer immunotherapy.

Tumor growth often creates hypoxic conditions within the tumor microenvironment, which can limit the effectiveness of therapies. To address this issue, a novel "all-in-one" nanoplatform called PCN-224(Hf)@Sorafenib@(PSM) has been developed. This nanoplatform utilizes PCN-224(Hf)-modified MnO2 and combines various therapeutic modalities-chemotherapy, chemodynamic therapy (CDT), photodynamic therapy (PDT), and radiotherapy (RT)-to enhance treatment efficacy. In the PSM nanoplatform, MnO2 decomposes H2O2 to produce oxygen (O2) and reacts with glutathione (GSH) to form Mn2+. This process catalyzes a Fenton-like reaction that generates hydroxyl radicals (·OH), facilitating CDT. When exposed to 635 nm light irradiation, the porphyrin ligand in PCN-224(Hf) produces singlet oxygen (1O2), while the Hf6 clusters contribute to the PDT effects. Furthermore, the nanoplatform enhances radiotherapy by harnessing high-energy radiation. Studies have demonstrated that PSM effectively kills solid tumors even in hypoxic conditions and significantly inhibits tumor growth. This innovative nanoplatform showcases high efficacy in multimodal synergistic tumor treatment, successfully integrating multiple therapeutic approaches to overcome the challenges posed by hypoxia.

Sterile and infection-associated inflammatory diseases are becoming increasingly prevalent worldwide. Conventional drug therapies often entail significant drawbacks, such as the risk of drug overdose, the development of drug resistance in pathogens, and systemic adverse reactions, all of which can undermine the effectiveness of treatments for these conditions. Nanomaterials (NMs) have emerged as a promising tool in the treatment of inflammatory diseases due to their precise targeting capabilities, tunable characteristics, and responsiveness to external stimuli. Ultrasound (US), a non-invasive and effective treatment method, has been explored in combination with NMs to achieve enhanced therapeutic outcomes. This review provides a comprehensive overview of the recent advances in the use of US-mediated NMs for treating inflammatory diseases. A comprehensive introduction to the application and classification of US was first presented, emphasizing the advantages of US-mediated NMs and the mechanisms through which US and NMs interact to enhance anti-inflammatory therapy. Subsequently, specific applications of US-mediated NMs in sterile and infection-associated inflammation were summarized. Finally, the challenges and prospects of US-mediated NMs in clinical translation were discussed, along with an outline of future research directions. This review aims to provide insights to guide the development and improvement of US-mediated NMs for more effective therapeutic interventions in inflammatory diseases.

Messenger RNA (mRNA)-based immunotherapies and protein in situ production therapies hold great promise for addressing theoretically all the diseases characterized by aberrant protein levels. The safe, stable, and precise delivery of mRNA to target cells via appropriate pharmaceutical strategies is a prerequisite for its optimal efficacy. In this review, we summarize the structural characteristics, mode of action, development prospects, and limitations of existing mRNA delivery systems from a pharmaceutical perspective, with an emphasis on the impacts from formulation adjustments and preparation techniques of non-viral vectors on mRNA stability, target site accumulation and transfection efficiency. In addition, we introduce strategies for synergistical combination of mRNA and small molecules to augment the potency or mitigate the adverse effects of mRNA therapeutics. Lastly, we delve into the challenges impeding the development of mRNA drugs while exploring promising avenues for future advancements.

Glioblastoma multiforme (GBM) is a highly aggressive and malignant brain tumor originating from glial cells, characterized by high recurrence rates and poor patient prognosis. The heterogeneity and complex biology of GBM, coupled with the protective nature of the blood-brain barrier (BBB), significantly limit the efficacy of traditional therapies. The rapid development of nanoenzyme technology presents a promising therapeutic paradigm for the rational and targeted treatment of GBM. In this review, the underlying mechanisms of GBM pathogenesis are comprehensively discussed, emphasizing the impact of the BBB on treatment strategies. Recent advances in nanoenzyme-based approaches for GBM therapy are explored, highlighting how these nanoenzymes enhance various treatment modalities through their multifunctional capabilities and potential for precise drug delivery. Finally, the challenges and therapeutic prospects of translating nanoenzymes from laboratory research to clinical application, including issues of stability, targeting efficiency, safety, and regulatory hurdles are critically analyzed. By providing a thorough understanding of both the opportunities and obstacles associated with nanoenzyme-based therapies, future research directions are aimed to be informed and contribute to the development of more effective treatments for GBM.

Cancer is a global health concern. Various therapeutic approaches, including chemotherapy, photodynamic therapy, and immunotherapy, have been developed for cancer treatment. Silica nanoparticles, quantum dots, and metal-organic framework (MOF)-based nanomedicines have gained interest in cancer therapy because of their selective accumulation in tumors via the enhanced permeability and retention (EPR) effect. However, bare nanoparticles face challenges including poor biocompatibility, low stability, limited drug-loading capacity, and rapid clearance by the reticuloendothelial system (RES). Gels with unique three-dimensional network structures formed through various interactions such as covalent and hydrogen bonds are emerging as promising materials for addressing these challenges. Gel hybridization enhances biocompatibility, facilitates controlled drug release, and confers cancer-targeting abilities to nanoparticles. This review discusses gel-nanoparticle hybrid systems for cancer treatment developed in the past five years and analyzes the roles of gels in these systems.

Neuroblastoma (NB) is an aggressive pediatric solid tumor that lacks efficient treatment. In the past few years, the use of engineered lymphocytes endowed with chimeric antigen receptors (CAR T), which improve their natural search and destroy skills against tumoral cells, has provided a highly valuable strategy to eradicate tumors in a specific and safe manner. Unfortunately, despite the excellent results achieved by these cell-based therapies in liquid tumors, their efficacy in the treatment of solid malignancies is usually modest due to the existence of several biological barriers which compromise their efficacy. Herein, a strategy to guide CAR T toward NB cells based on the use of nanometric bispecific T engagers (NBTEs) is presented. These novel bispecific nanoplatforms are based on liposomes and protocells doubly functionalized with synthetic targeting moieties (para-aminobenzylguanidine and fluorescein) able to selectively bind to membrane cell receptors of NB and anti-FITC CAR T, respectively. The binding process of NBTEs to NB cells was monitored by confocal fluorescence microscopy showing the excellent capacity of these nanodevices to place fluorescence labels on the surface of the malignant cells. Then, NB cells previously incubated in the presence of NBTEs were rapidly detected and destroyed by anti-FITC CAR T, which confirmed the excellent capacity of these nanoplatforms to improve the natural capacity of CAR T to eradicate malignant cells. Finally, the high versatility of the NBTE design and its easy-to-tune nature would allow their rapid application to different types of solid tumors.

Hepatocellular carcinoma is one of the leading causes of cancer deaths globally and a key hindrance to extending life expectancy. Celastrol (CEL) demonstrates excellent antitumor activity, but faces challenges like low solubility and a narrow therapeutic window, limiting its clinical application. To address these limitations, drug combinations and nano-delivery systems have emerged as effective solutions. Curcumin (CUR), known for its antitumor and hepatoprotective effects, also exhibits good biocompatibility and the ability to mitigate drug-induced liver injury. Considering the complementary properties of CEL and CUR, including CEL's potent antitumor activity and CUR's hepatoprotective effects, we developed a novel self-assembling nanodrug delivery system (CCPN) for the co-loading of both compounds. CCPN nanoparticles were constructed through non-covalent interactions, including hydrogen bonding, π-π stacking, and electrostatic forces, which confer good stability and significantly enhance the solubility and bioavailability of CEL and CUR. Extensive in vitro and in vivo experiments demonstrated that CCPN effectively reduced CEL-induced hepatotoxicity in zebrafish and mouse models, exhibiting good biosafety. Additionally, CUR's fluorescence provides a unique advantage for real-time monitoring of drug distribution and release, facilitating the tracking of therapeutic progress. Furthermore, CCPN nanoparticles enhanced delivery efficiency in HepG2 cells, exhibiting superior anti-liver tumor outcomes, which are associated with the promotion of apoptosis in tumor cells. This study presents CCPN as a promising therapeutic strategy for hepatocellular carcinoma, integrating reduced hepatotoxicity, self-monitoring capabilities, and superior therapeutic efficacy.

Over the last two decades, advancements in nanomaterials and nanoscience have paved the path for the emergence of nano-medical convergence science, significantly impacting healthcare. In our review, we highlight how these advancements are applied in various biomedical technologies such as drug delivery systems, bio-imaging for diagnostic and therapeutic purposes. Recently, novel inorganic nanohybrid drugs have been developed, combining multifunctional inorganic nanomaterials with therapeutic agents (known as inorganic medicinal nanoarchitectonics). These innovative drugs are actively utilized in cutting-edge medical treatments, including targeted anti-cancer therapy, photo and radiation therapy, and immunotherapy. This review provides a detailed overview of the current development status of inorganic medicinal nanoarchitectonics and explores potential future directions in their advancements.

Cardiovascular diseases (CVDs) represent a leading global health crisis, significantly impairing patients' quality of life and posing substantial risks to their survival. Conventional therapies for CVDs often grapple with challenges such as inadequate targeting precision, suboptimal therapeutic efficacy, and potential adverse side effects. To address these shortcomings, researchers are intensively developing advanced drug delivery systems characterized by high specificity and selectivity, excellent biodegradability, superior biocompatibility, and minimal toxicity. These innovative systems enable the precise delivery of pharmaceuticals with high drug-loading capacities, minimal leakage, and expansive specific surface areas, thereby enhancing therapeutic outcomes. In this review, we summarize and classify various drug delivery materials targeting CVDs and application values. We also evaluate the feasibility and efficacy of viral and non-viral vectors for the treatment of CVDs, the existing limitations and application prospects are also discussed. We hope that this review will provide new perspectives for the future development of drug delivery systems for the treatment of CVDs, ultimately contributing to improved patient care and outcomes.

Conventional cancer therapies such as chemotherapy face challenges such as poor tumor targeting, systemic toxicity, and drug resistance. Nanotechnology offers solutions through advanced drug delivery systems that preferentially accumulate in tumors while avoiding healthy tissues. Recent innovations have enabled the optimization of engineered nanocarriers for extended circulation and tumor localization via both passive and active targeting mechanisms. Passive accumulation exploits the leaky vasculature of tumors, whereas active strategies use ligands to selectively bind cancer cell receptors. Multifunctional nanoparticles also allow the combination of imaging, multiple therapeutic modalities and on-demand drug release within a single platform. Overall, precisely tailored nanotherapeutics that leverage unique pathophysiological traits of malignancies provide opportunities to overcome the limitations of traditional treatment regimens. This emerging field promises more effective and personalized nanomedicine approaches to detect and treat cancer. The key aspects highlighted in this review include the biological barriers associated with nanoparticles, rational design principles to optimize nanocarrier pharmacokinetics and tumor uptake, passive and active targeting strategies, multifunctionality, and reversal of multidrug resistance.

Cuproptosis exhibits enormous application prospects in treatment. However, cuproptosis-based therapy is impeded by the limited intracellular copper ions, the nonspecific delivery, uncontrollable release, and chelation of endogenous overproduced glutathione (GSH). In this work, an ultrasound-triggered nanosonosensitizer (p-TiO2-Cu(I)) was constructed for Cu(I) delivery, on-demand release, GSH consumption, and deeper tissue response. When the nanomedicine was internalized into the tumor cells, ultrasound (US) induced the nanosonosensitizer to produce reactive oxygen species (ROS) to achieve sonodynamic therapy (SDT). GSH, acting as a hole trapping agent, improved the efficiency of SDT. Meanwhile, the downgrade of GSH was beneficial to cuproptosis and oxidative damage-based SDT in return. What is more, the US could regulate the release behavior of Cu(I). Cu(I) bonded to mitochondrial proteins and then aggregated the lipoylated protein, bringing about the turbulence of the tricarboxylic acid cycle. The combination of SDT and cuproptosis showed high matching to induce efficient cuproptosis and may inspire other cuproptosis-based nanosonosensitizer designs.

Natural enzyme systems possess extraordinary functions and characteristics, making them highly appealing for use in eco-friendly technologies and innovative cancer treatments. However, their inherent instability and structural complexity often limit their practical applications, leading to the exploration of biomolecular nanozyme alternatives. Supramolecular nanozymes, constructed using self-assembly techniques and various non-covalent interactions, have emerged as a promising solution. Amino acids, peptides, and protein motifs offer flexible building blocks for constructing these nanozymes. Importantly, the well-defined structural regulation mechanisms of biomolecular nanozymes, along with their unique properties as fundamental biological modules in living systems-such as selectivity, permeability, retention, and biocompatibility-present new opportunities for cancer therapy. This review highlights recent advances in supramolecular self-assembled nanozymes, including peroxidases, oxidases, catalases, superoxide dismutases, and other nanozyme systems, as building blocks for tumor therapy. Additionally, it discusses precise functional modulation through supramolecular non-covalent interactions and their therapeutic applications in targeting the tumor microenvironment. These studies provide valuable insights that may inspire the design of novel supramolecular nanozymes with enhanced catalytic selectivity, biocompatibility, and tumor-killing efficacy.

Immunogenic cell death (ICD) has recently emerged as a promising strategy in reinforcing anti-PD-L1 blockade immunotherapy of triple-negative breast cancer (TNBC). The CDK4/6 inhibitor palbociclib (PAL), as a clinical star medicine targeting the cell cycle machinery, is an ideal candidate for fabricating a highly efficient ICD inducer for TNBC chemoimmunotherapy. However, the frequently observed chemoresistance and clinical adverse effects, as well as significant antagonistic effects when co-administered with certain chemotherapeutics, have seriously restricted the efficiency of PAL and the feasibility of combination strategies. Herein, we screened and identified six self-assembled natural pentacyclic triterpenoid (PT) molecules that can serve as competent co-administration nanoplatforms for the synergistic or combined delivery of PAL. Analysis of two representative PT-PAL nano-assemblies validated that PT-mediated co-assembly enhances the cytotoxicity and synergy of PAL by inhibiting the PI3K/AKT/mTOR signaling pathway, rather than directly targeting CDK4/6 proteins. Importantly, the PAL nanoassemblies exhibited multiple favorable therapeutic features and stronger accumulative ICD induction, ensuring highly efficient synergistic anti-PD-L1 chemoimmunotherapy by simultaneously facilitating T-cell immune response and reversing the immunosuppressive tumor microenvironment. This study offers possibilities for improving the anticancer efficacy of CDK4/6 inhibitors and potential avenues for clinical applications of chemoimmunotherapy in treating TNBC.

The advent of autonomous nanomotors presents exciting opportunities for nanodrug delivery. However, significant potential remains for enhancing the asymmetry of nanomotors and advancing the development of second near-infrared (NIR-II) light-propelled nanomotors capable of operating within deep tissues. Herein, we developed a dual-ligand assisted anisotropic assembly strategy that enables precise regulation of the interfacial energy between selenium (Se) nanoparticle and periodic mesoporous organosilica (PMO). This strategy facilitates the controllable anisotropic growth of PMO on the Se nanoparticle, leading to the formation of Se&PMO Janus nanohybrids. The exposure ratio of the Se subunit within the Janus nanohybrids can be finely tuned from 0% to 75%. Leveraging the transformability of the Se subunit, a variety of functional MxSe&PMO Janus nanocomposites (MxSe denotes metal selenide) were further derived. As a proof of concept, CuSe&PMO Janus nanohybrids, with NIR-II photothermal properties, were employed as NIR-II light-driven nanomotors. By precisely controlling the exposure ratio of the CuSe subunit within the Janus nanostructure, these CuSe&PMO nanomotors achieved optimal self-propulsion, thus enhancing cellular uptake and promoting deep tumor penetration. Furthermore, the high loading capacity and hydrophobic framework of the PMO subunit enabled the incorporation of hydrophobic disulfiram, thereby significantly boosting the efficacy of synergistic active-motion photothermal therapy.

Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α v β 3 because of the multivalent interactions between larger active nanoparticles and integrin α v β 3. In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.

Abemaciclib (ABE) is an anticancer drug that suffers from low bioavailability and multidrug resistance. This study aims to develop ABE-loaded solid lipid nanoparticles (ABE-SLNs), which will enhance drug solubility and lead to increased cellular uptake and enhanced cytotoxicity when delivering tumor cells.

Melt emulsification followed by ultrasonication was used as a method of preparation and Quality-by-Design (QbD) was utilized to optimize ABE-SLNs.

The optimized ABE-SLNs consist of Precirol-ATO5 as a lipid and Brij-58 as a surfactant. The particle size, PDI value, and zeta potential of the optimized formulation were 170.4 ± 0.49 nm, 0.25 ± 0.014, and -26.4 ± 0.1 mV, respectively. It also showed sustained release behavior and a high entrapment efficiency of 79.96%. ABE-SLNs exhibited enhanced anticancer activity in the MDA-MB-231 and T47D breast cancer cell lines compared to pure ABE. In Caco-2 human colonic cell lines, ABE-SLNs also showed increased cellular uptake.

The use of QbD to achieve high entrapment efficiency and sustained release in ABE-SLNs, coupled with enhanced cellular uptake and cytotoxicity, represents a novel approach that could set a new standard for nanoparticle-based drug delivery systems.

Cancer remains one of the most challenging health issues globally, demanding innovative therapeutic approaches for effective treatment. Nanoparticles, particularly those composed of gold, silver, and iron oxide, have emerged as promising candidates for changing cancer therapy. This comprehensive review demonstrates the landscape of nanoparticle-based oncological interventions, focusing on the remarkable advancements and therapeutic potentials of gold, silver, and iron oxide nanoparticles. Gold nanoparticles have garnered significant attention for their exceptional biocompatibility, tunable surface chemistry, and distinctive optical properties, rendering them ideal candidates for various cancer diagnostic and therapeutic strategies. Silver nanoparticles, renowned for their antimicrobial properties, exhibit remarkable potential in cancer therapy through multiple mechanisms, including apoptosis induction, angiogenesis inhibition, and drug delivery enhancement. With their magnetic properties and biocompatibility, iron oxide nanoparticles offer unique cancer diagnosis and targeted therapy opportunities. This review critically examines the recent advancements in the synthesis, functionalization, and biomedical applications of these nanoparticles in cancer therapy. Moreover, the challenges are discussed, including toxicity concerns, immunogenicity, and translational barriers, and ongoing efforts to overcome these hurdles are highlighted. Finally, insights into the future directions of nanoparticle-based cancer therapy and regulatory considerations, are provided aiming to accelerate the translation of these promising technologies from bench to bedside.

Cancer immunotherapy holds significant promise for improving cancer treatment efficacy; however, the low response rate remains a considerable challenge. To overcome this limitation, advanced catalytic materials offer potential in augmenting catalytic immunotherapy by modulating the immunosuppressive tumor microenvironment (TME) through precise biochemical reactions. Achieving optimal targeting precision and therapeutic efficacy necessitates a thorough understanding of the properties and underlying mechanisms of tumor-targeted catalytic materials. This review provides a comprehensive and systematic overview of recent advancements in tumor-targeted catalytic materials and their critical role in enhancing catalytic immunotherapy. It highlights the types of catalytic reactions, the construction strategies of catalytic materials, and their fundamental mechanisms for tumor targeting, including passive, bioactive, stimuli-responsive, and biomimetic targeting approaches. Furthermore, this review outlines various tumor-specific targeting strategies, encompassing tumor tissue, tumor cell, exogenous stimuli-responsive, TME-responsive, and cellular TME targeting strategies. Finally, the discussion addresses the challenges and future perspectives for transitioning catalytic materials into clinical applications, offering insights that pave the way for next-generation cancer therapies and provide substantial benefits to patients in clinical settings.