International Journal Of Nanomedicine[JOURNAL]
Sun
200 papers
Lipid-Based Nanocarriers for Curcumin Delivery: A Promising Strategy in The Management of Inflammatory Diseases.
Sitompul JEN, Rahma MN, Afandi F … +3 more , Elamin KM, Mohammed AFA, Wathoni N
Int J Nanomedicine · 2026 · PMID 42220974 · Full text
Inflammation is a key pathophysiological process underlying a broad spectrum of chronic disorders, including rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, neurodegenerative diseases, and metabolic syn...
Inflammation is a key pathophysiological process underlying a broad spectrum of chronic disorders, including rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, neurodegenerative diseases, and metabolic syndrome, and is closely linked to oxidative stress, immune dysregulation, and sustained production of pro-inflammatory mediators. Curcumin, a bioactive polyphenol derived from , has been extensively studied because of its pleiotropic anti-inflammatory mechanisms, however, its therapeutic translation is substantially limited by poor aqueous solubility, chemical instability, rapid metabolism, and low systemic bioavailability. In this context, lipid-based nanocarriers, notably liposomes, solid lipid nanoparticles, nanostructured lipid carriers, phytosomes, ethosomes, niosomes, nanoemulsions, self-nano-emulsifying drug delivery systems (SNEDDS), transfersomes, lipid nanocapsules, lipid micelles, spanlastic, and cubesomes, have emerged as promising formulation strategies to improve curcumin delivery. These platforms can enhance the solubility, stability, absorption, and pharmacokinetic performance of curcumin and, in selected cases, facilitate more efficient accumulation at inflamed sites. This review critically appraises recent advances in lipid-based nanocarrier systems for curcumin delivery in inflammatory diseases and addresses the principal formulation, translational, and clinical challenges that remain to be resolved.
Biological Safety Analysis of Nanoparticles: Exploring Toxicity, Mechanisms, and Safety Factors for Pharmaceuticals.
Huang A, Jiang Z, Liang Z … +5 more , Tang N, Liu J, Yu XA, Wang B, Wang X
Int J Nanomedicine · 2026 · PMID 42220973 · Full text
BACKGROUND: With the rapid advancement of nanotechnology, nanoparticles (NPs) have been widely applied in fields such as drug delivery, medical imaging, and disease therapy, owing to their unique physicochemical and biol...
BACKGROUND: With the rapid advancement of nanotechnology, nanoparticles (NPs) have been widely applied in fields such as drug delivery, medical imaging, and disease therapy, owing to their unique physicochemical and biological properties. However, as NPs become increasingly prevalent in industrial production and daily life, the frequency and routes of human exposure have significantly increased, making the safety issues arising from their interactions with biological systems a major focus of public health concern. METHODS: This review systematically retrieved relevant literature from databases including PubMed and Web of Science over the past 15 years, focusing on toxicological studies of NPs at the organ and system levels. RESULTS: It summarizes the key mechanisms of nanotoxicity and the critical factors influencing safety evaluation. The findings indicate that NPs toxicity primarily targets the liver, kidneys, nervous system, and immune system. Oxidative stress, inflammatory responses, and DNA damage represent the major common mechanisms of nanotoxicity, while physicochemical properties such as particle size, surface charge, and protein corona formation are the core factors affecting safety. CONCLUSION: Based on these findings, this review analyzes the limitations of existing research in the context of the current research landscape, aiming to provide theoretical support for the safe application of NPs and to offer a reference for the establishment of a systematic nanotoxicity safety evaluation framework.
Thermosensitive in situ Hydrogel Based on Benzalkonium Chloride-Loaded Selenium-Doped Mesoporous Silica Nanoparticles for Diabetic Chronic Wound Treatment.
Liu Y, Wang K, Li Y … +6 more , Lv K, Yang M, Li Z, Bai X, Gao F, Wang Y
Int J Nanomedicine · 2026 · PMID 42220972 · Full text
BACKGROUND: Diabetic chronic wounds are characterized by persistent infection, excessive oxidative stress, impaired angiogenesis, and prolonged inflammation, resulting in delayed healing. Current wound dressings lack the...
BACKGROUND: Diabetic chronic wounds are characterized by persistent infection, excessive oxidative stress, impaired angiogenesis, and prolonged inflammation, resulting in delayed healing. Current wound dressings lack the ability to simultaneously regulate these pathological processes. METHODS: A multifunctional composite hydrogel was developed by incorporating benzalkonium chloride (BAC)-loaded selenium-doped mesoporous silica nanoparticles (Se-MSNs) into a PF127 matrix. In this system, BAC provides antibacterial activity, Se-MSNs enable redox regulation and immunomodulation, and PF127 serves as a delivery platform for localized retention and sustained release. The physicochemical properties, antibacterial activity, antioxidant capacity, pro-angiogenic effects, and anti-inflammatory performance were evaluated in vitro, followed by therapeutic assessment in a diabetic mouse wound model. RESULTS: The composite hydrogel exhibited effective antibacterial activity against Staphylococcus aureus and Escherichia coli, reduced intracellular reactive oxygen species, promoted endothelial cell migration and tube formation, and modulated inflammatory cytokine expression in vitro. In vivo, the hydrogel significantly accelerated wound closure, enhanced collagen deposition and angiogenesis, and alleviated excessive inflammation in diabetic wounds. CONCLUSION: The therapeutic effects of the composite hydrogel are attributed to the restoration of redox homeostasis and the coordinated regulation of inflammation resolution and vascular regeneration. This study presents a multifunctional biomaterial strategy for improving the healing of diabetic chronic wounds.
Synergistic Effect of Doxorubicin-Thermo-Iodized Oil Pickering Emulsions on the Interventional Embolization-Chemotherapy- Immunity of VX2 Rabbit Liver Cancer.
Li L, Xie W, Sun H … +6 more , Yu H, Wang C, Zheng M, Shi P, Tian H, Xiong T
Int J Nanomedicine · 2026 · PMID 42220971 · Full text
BACKGROUND: Tumor recurrence and metastasis are important factors affecting the efficacy of transhepatic arterial chemoembolization. To prolong the survival of patients, comprehensive interventional therapy and antitumor...
BACKGROUND: Tumor recurrence and metastasis are important factors affecting the efficacy of transhepatic arterial chemoembolization. To prolong the survival of patients, comprehensive interventional therapy and antitumor drugs that can control their release need to be developed. METHODS: Poly(N-isopropylacrylamide-co-acrylic acid) nanogels are firstly self-assembled with doxorubicin, the constructed doxorubicin-loaded nanogels were then emulsified with iodized oil under high-shear conditions to form doxorubicin-iodized oil nanogel suspensions (Dox-TIPE). The structural characteristics, thermosensitive properties and rheological properties were evaluated. The in vitro biocompatibility and drug release behavior of Dox-TIPE were assayed and in vivo interventional therapy was examined in a VX2 rabbit liver cancer model. RESULTS: Dox-TIPE can effectively exert the dual advantages of chemoembolization therapy, achieving a superior therapeutic effect on inhibiting rabbit liver tumor growth. It promotes TUNEL expression in the tumor boundary region while reducing Ki67 expression, which results in decreased tumor cell proliferation and increased apoptosis rates. Furthermore, Dox-TIPE effectively suppresses the expressions of HIF-1α, VEGF, and CD31 in tumor target areas, thereby preventing the formation of tumor neovascularization and collateral circulation. CONCLUSION: We successfully produced Dox-TIPE which offers a multifunctional platform combining embolization, chemotherapy, imaging, and immunomodulation. This novel embolic material shows strong potential to address current limitations of TACE in liver cancer treatment and may serve as a promising candidate for next-generation embolization therapies.
Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer [Retraction].
Int J Nanomedicine · 2026 · PMID 42205871 · Full text
[This retracts the article DOI: 10.2147/IJN.S150237.].
[This retracts the article DOI: 10.2147/IJN.S150237.].
Natural Compound-Loaded PLGA Nanocarriers for Infected Wound Management: A Review.
Norouzi E, Hemmati J, Chehelgerdi M … +1 more , Arabestani MR
Int J Nanomedicine · 2026 · PMID 42205870 · Full text
Infected wounds remain a significant clinical challenge due to persistent microbial colonization, biofilm formation, delayed tissue regeneration, and prolonged healing processes. Poly (lactic-co-glycolic acid) (PLGA), a...
Infected wounds remain a significant clinical challenge due to persistent microbial colonization, biofilm formation, delayed tissue regeneration, and prolonged healing processes. Poly (lactic-co-glycolic acid) (PLGA), a biodegradable and biocompatible polymer approved by the FDA, has gained increasing attention as a carrier for natural compounds because of its ability to provide controlled and sustained drug release, improve compound stability, and enhance therapeutic efficacy. This review summarizes recent advances in PLGA-based formulations loaded with natural compounds for the treatment of infected wounds. Findings from various studies demonstrate that these nanostructures promote wound healing through antimicrobial and anti-biofilm activities, antioxidant and anti-inflammatory effects, stimulation of angiogenesis, collagen deposition, and re-epithelialization. In addition, this review discusses different aspects of PLGA-based nanostructures, including fabrication and synthesis strategies, drug release behaviors, and bacterial biofilm-targeting mechanisms, which may play an important role in the development of novel nanoparticle-based therapeutic approaches for overcoming current challenges associated with infected wound management. Overall, the delivery of natural compounds through PLGA-based systems represents a promising strategy for the effective treatment of infected wounds and the advancement of next-generation wound care therapies. This review, with a focus on PLGA-natural compound systems for the treatment of infected wounds, provides a coherent synthesis of dispersed studies and, by emphasizing antibiofilm mechanisms and controlled drug release, offers an integrated perspective for a better understanding of the therapeutic potential of these nanoplatforms.
Research Progress of Ferrosoferric Oxide Nanoparticles in Bone Regeneration and Disease Treatment.
Song JB, Li JY, Ding YB … +6 more , Yang SZ, Sun L, Yang Y, Lin ZX, Feng YC, Liu FX
Int J Nanomedicine · 2026 · PMID 42205869 · Full text
Ferrosoferric oxide nanoparticles (FeONPs), with unique magnetic properties and biocompatibility, have shown great promise for application in the treatment of bone regeneration and diseases in recent years. Bone-related...
Ferrosoferric oxide nanoparticles (FeONPs), with unique magnetic properties and biocompatibility, have shown great promise for application in the treatment of bone regeneration and diseases in recent years. Bone-related diseases, such as osteoporosis, bone defects and bone tumors, seriously affect the health and quality of life of millions of people around the world, and existing treatments have many limitations, such as low bioavailability, significant side effects, and lack of precision in drug delivery. FeONPs could realize precise magnetic targeting therapy through an external magnetic field to efficiently deliver drugs or growth factors to the focal area, and at the same time, with the aid of the magnetic heating effect, could regulate osteoclasts and osteoblasts. At the same time, FeONPs could regulate the balance between osteoclasts and osteoblasts, restore the homeostasis of bone metabolism and accelerate bone healing. In addition, as a scaffold material, it could also provide support for bone tissue regeneration, achieving a synergistic treatment for bone defect repair and regeneration. In this paper, we systematically review the synthesis, characterization, clinical application and biosafety of FeONPs, focusing on the potential of FeONPs in the treatment of osteoporosis, bone defect repair, and bone tumors, and looking forward to the development direction of FeONPs in precision medicine and personalized treatment, and presenting the current challenges and future research priorities.
Enhanced Antitumor Effects by Docetaxel/LL37-Loaded Thermosensitive Hydrogel Nanoparticles in Peritoneal Carcinomatosis of Colorectal Cancer [Retraction].
Int J Nanomedicine · 2026 · PMID 42205868 · Full text
[This retracts the article DOI: 10.2147/IJN.S89066.].
[This retracts the article DOI: 10.2147/IJN.S89066.].
CA9-Targeted Liposomal Delivery of siETS1 Inhibits Clear Cell Renal Cell Carcinoma Progression by Disrupting the ETS1/MYC Regulatory Axis.
Ye Y, Sun J, Zhang Y … +2 more , Wang S, Meng Z
Int J Nanomedicine · 2026 · PMID 42205867 · Full text
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a highly aggressive malignancy with a high rate of recurrence and limited therapeutic options. Carbonic anhydrase IX (CA9) is characteristically overexpressed on the...
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a highly aggressive malignancy with a high rate of recurrence and limited therapeutic options. Carbonic anhydrase IX (CA9) is characteristically overexpressed on the surface of ccRCC cells, making it a promising target for site-specific drug delivery. However, identifying the key molecular drivers of ccRCC progression and developing efficient, targeted nanomedicines remain critical challenges in current research. METHODS: Bioinformatics analysis of TCGA and single-cell RNA sequencing data was used to elucidate the ETS1/MYC axis. Direct transcriptional regulation of MYC by ETS1 was experimentally validated by chromatin immunoprecipitation-quantitative PCR (ChIP-PCR) and dual-luciferase reporter assays. An optimized CA9-targeting peptide, CaIX-P7, was designed via computational modeling and mutation screening, with affinity validated by surface plasmon resonance (SPR). siETS1-loaded liposomal nanoparticles (LNPs) were prepared using microfluidics and surface-functionalized with CaIX-P7 (ETS1@Lip-CAIX). The nanoparticles were characterized for size, zeta potential, and encapsulation efficiency. Therapeutic efficacy was evaluated in ccRCC cell lines (786-O, A-498), patient-derived organoids (PDO), and nude mouse xenograft models. RESULTS: Single-cell analysis identified ETS1 and MYC as synergistically activated transcription factors within tumor epithelial cells. Mechanistically, ChIP-PCR and dual-luciferase assays demonstrated that ETS1 promotes MYC transcription through this specific binding site, establishing ETS1 as a direct transcriptional activator of MYC. The optimized peptide CaIX-P7 demonstrated superior binding affinity to CA9 (Kd=52.96 nM) compared to its precursor. The engineered ETS1@Lip-CAIX nanoparticles exhibited a stable size of 154.8 nm and high siRNA encapsulation efficiency (89.1%). Systematic evaluation revealed that ETS1@Lip-CAIX effectively silenced the ETS1/MYC axis, leading to significant growth inhibition across all models, including patient-derived 3D organoids and in vivo xenografts, showed no discernible morphological alterations or pathological damage in major organs. CONCLUSION: This study identifies the ETS1/MYC axis as a novel therapeutic target in ccRCC. We further successfully developed a CA9-targeted nanoplatform, ETS1@Lip-CAIX, which exhibits robust anti-tumor efficacy by disrupting this newly discovered regulatory hub. These findings provide a foundation for future translational studies of ccRCC.
Molecular Mechanisms and Biomedical Applications of Ferritin Nanocages: A Comprehensive Review of Self-Assembly, Engineering, and Multifunctional Delivery Platforms.
Gao F, Wu Y, Chen X … +7 more , Chen J, Liu Y, Huang A, Fu Y, Chen D, Lin F, Zhou Y
Int J Nanomedicine · 2026 · PMID 42205866 · Full text
Ferritin is a heteropolymer or homopolymer composed of 24 polypeptides forming a cage-shaped sphere. Its main function is to maintain soluble and non-toxic states of iron ions in the body. In mammals, ferritin is primari...
Ferritin is a heteropolymer or homopolymer composed of 24 polypeptides forming a cage-shaped sphere. Its main function is to maintain soluble and non-toxic states of iron ions in the body. In mammals, ferritin is primarily located in the cytoplasm and the mitochondria. Cytoplasmic ferritin consists of heavy (H) and light (L) subunits, whereas mitochondrial ferritin is a homopolymer composed exclusively of a single subunit type. A notable feature of ferritin is its ability to self-assemble into nanocages in vitro, which is reversible and controllable. This unique property has enabled its widespread application in various fields including drug delivery, disease diagnosis, and vaccine development. In this review, we provide a comprehensive overview of ferritin, focusing on the following aspects: 1) structural characteristics, biological functions, dynamics, and molecular mechanisms underlying ferritin self-assembly, 2) recent advances and applications of ferritin-based self-assembled nanocages in biomedicine and bioengineering, and 3) progress in the molecular modification of ferritin using genetic engineering techniques. Additionally, we critically examined the current limitations of ferritin in research and practical applications, and proposed potential strategies for further improvement, with the aim of providing insights into the future development and utilization of ferritin in medical and scientific contexts. This work integrates the kinetics and molecular mechanisms of ferritin self-assembly with advanced genetic engineering strategies, offering a systematic framework for the rational design of ferritin-based multifunctional platforms.
Metal-Organic Framework Nanoplatform Synergizes Fenton-Driven Ferroptosis and Photodynamic Apoptosis for Enhanced Hepatocellular Carcinoma Therapy.
Kong S, Lin H, Liu Y … +3 more , Tang R, Li H, Lin L
Int J Nanomedicine · 2026 · PMID 42205865 · Full text
BACKGROUND: Hepatocellular carcinoma (HCC) is notorious for its dismal prognosis and resistance to conventional therapies. The integration of multiple cell death mechanisms emerges as a promising strategy to combat the h...
BACKGROUND: Hepatocellular carcinoma (HCC) is notorious for its dismal prognosis and resistance to conventional therapies. The integration of multiple cell death mechanisms emerges as a promising strategy to combat the heterogeneity of this malignancy. PURPOSE: Herein, we engineered a multifunctional nanoplatform, TPMIL101-TCPP@Lip-HA, by encapsulating the photosensitizer TCPP and chemotherapeutic agent triptolide (TP) within a metal-organic framework (MIL101), followed by surface modification with liposomes and hyaluronic acid. This sophisticated drug delivery system capitalizes on the enhanced permeability and retention effect to achieve tumor-specific accumulation. METHODS: Upon reaching the tumor site, TPMIL101-TCPP@Lip-HA undergoes gradual disintegration, releasing its therapeutic payload. The tumor microenvironment facilitates the reduction of Fe³⁺ to Fe²⁺, triggering ferroptosis through the Fenton reaction. Simultaneously, laser irradiation activates TCPP to generate cytotoxic reactive oxygen species, initiating photodynamic therapy-induced apoptosis. The concomitant accumulation of lipid peroxides synergistically amplifies the ferroptotic cascade. RESULTS: studies confirm potent anti-HCC efficacy with reduced TP toxicity. Mechanistic studies elucidate that TPMIL101-TCPP@Lip-HA orchestrates ferroptosis through modulation of iron storage and lipid oxidation proteins, while concurrently inducing apoptosis via the cytochrome c/Apaf-1/caspase signaling axis. CONCLUSION: These findings collectively underscore TPMIL101-TCPP@Lip-HA as a potent therapeutic nanoplatform capable of arresting HCC progression.
Vesicle-Mediated Delivery of Carbon Dots: Synthesis, Properties, and Biomedical Applications.
Xu X, Zhao J, Tao S … +4 more , Miao C, Li C, Cui W, Guo Z
Int J Nanomedicine · 2026 · PMID 42205864 · Full text
Carbon dots (CDs), as an emerging class of carbon nanomaterials, exhibit exceptional optical properties, biocompatibility, and functional tunability, rendering them highly promising for applications in biosensing, bioima...
Carbon dots (CDs), as an emerging class of carbon nanomaterials, exhibit exceptional optical properties, biocompatibility, and functional tunability, rendering them highly promising for applications in biosensing, bioimaging, antibacterial therapy, and phototherapy. However, their small size leads to a poor enhanced-permeation-and-retention (EPR) effect and inadequate targeting capability, which hinders their further translation into biomedical applications. Vesicles, including natural extracellular vesicles (EVs), liposomes, and synthetic vesicles, serve as ideal nanocarriers due to their unique bilayer structure, excellent biocompatibility, and intrinsic targeting properties. The integration of CDs with vesicles forms a novel multifunctional hybrid system, which can effectively address the delivery limitations of CDs while endowing vesicles with additional functionalities such as fluorescence tracing and phototherapeutic effects. This review systematically summarizes the synthesis methods (top-down and bottom-up) and key physicochemical (structural and optical) properties of CDs, as well as the classification and characteristics of various vesicles. Furthermore, it focuses on the construction strategies, interaction mechanisms, and loading methods of CD-vesicle hybrids, and comprehensively elaborates on their applications in targeted drug delivery, bioimaging, tumor therapy, antibacterial treatment, and wound healing. In addition, we critically discuss the key bottlenecks currently limiting the clinical translation of CD-vesicle hybrid therapeutics, including the thermodynamic limitations of drug/CD loading efficiency, burst release of payloads, in vivo pharmacokinetic behavior, and the effects of CDs on vesicle interfacial stability and leakage kinetics. Finally, the current challenges (e.g. unclear interaction mechanisms, limited scalable production, and narrow application scope) and future development directions (e.g. expanding antimicrobial applications, promoting clinical translation, and exploring CD self-assembled vesicles) of CD-vesicle hybrid systems are discussed, aiming to provide a comprehensive reference for the rational design and biomedical application of CD-vesicle hybrid nanomaterials.
Enhancing Therapeutic Efficacy Through Tailored Pharmacokinetics: A Review of Mesoporous Silica Nanoparticle-Based Delivery Systems.
Aulifa DL, Maharani A, Purnomo KG … +7 more , Salsabilla RA, Fahlevi ZA, Pramudita FW, Wibisono TTDW, Amaliah S, Subra L, Budiman A
Int J Nanomedicine · 2026 · PMID 42199662 · Full text
Low solubility and bioavailability represent major challenges in drug development, resulting in sub-optimal pharmacokinetic profiles, including poor gastrointestinal absorption and limited systemic exposure. Mesoporous s...
Low solubility and bioavailability represent major challenges in drug development, resulting in sub-optimal pharmacokinetic profiles, including poor gastrointestinal absorption and limited systemic exposure. Mesoporous silica nanoparticles (MSNs) have emerged as promising drug delivery systems due to their high surface area, tunable pore size, and high pore volume, which enable enhanced drug loading and stabilization of drugs in an amorphous state. These properties are critical for improving dissolution behavior. Numerous studies confirm that drug encapsulation into MSNs significantly enhances the dissolution rate, leading to substantial pharmacokinetic improvements-specifically increased Area Under the Curve (AUC) and higher Maximum Plasma Concentration (Cmax)-which are directly correlated with enhanced systemic exposure and the potential for improved therapeutic efficacy for poorly soluble drugs. These comprehensive findings indicate that MSN-based delivery systems offer a powerful strategy to overcome the intrinsic pharmacokinetic limitations of poorly soluble compounds and warrant further investigation into their long-term safety and clinical application.
Research Progress on Mesenchymal Stem Cells-Derived Small Size Vesicles for the Treatment of Liver Diseases.
Meng C, Liu M, Qi Q … +4 more , Cao L, Lei Q, Liu X, Wang M
Int J Nanomedicine · 2026 · PMID 42199661 · Full text
Liver disease is a major public health challenge, accounting for a substantial burden of mortality and morbidity worldwide. Currently, liver transplantation is the gold standard for treating end-stage liver diseases. How...
Liver disease is a major public health challenge, accounting for a substantial burden of mortality and morbidity worldwide. Currently, liver transplantation is the gold standard for treating end-stage liver diseases. However, it is affected by the shortage of organ sources and immune rejection. Mesenchymal stem cells (MSCs) can be used as an alternative therapy for liver diseases, especially in cases of liver cirrhosis, liver failure and complications of liver transplantation. However, MSCs may have potential effects on tumor occurrence. MSCs derived small size vesicles are nanoscale extracellular vesicles (EVs) which secreted by MSCs. MSCs derived small size vesicles are characterized by a lipid bilayer membrane, which encapsulate and transport various biomolecules such as proteins and miRNAs. Compared to MSCs, MSCs derived small size vesicles showed more advantages including lower tumor occurrence and lower toxicity. It has been found that MSCs derived small size vesicles ameliorate liver diseases via regulating lipid metabolism, inhibiting apoptosis, promoting regeneration, suppressing inflammation, drug delivery and so on. Based on the important role of MSCs derived small size vesicles in liver diseases treatment, this review aims to summarize the biological processes of small size vesicles with focusing on the effect of MSCs derived small size vesicles on different liver diseases. Additionally, we also discussed the potential future directions for small size vesicles research, including the challenges to be overcome and the prospects for clinical applications. This review provides theoretical support of MSCs derived small size vesicles as a potential therapeutic agent for liver disease in humans.
Selective Laser Sintering Fabrication of Nano-Hydroxyapatite/Poly-ε-Caprolactone Scaffolds for Bone Tissue Engineering Applications [Retraction].
Int J Nanomedicine · 2026 · PMID 42199660 · Full text
[This retracts the article DOI: 10.2147/IJN.S50685.].
[This retracts the article DOI: 10.2147/IJN.S50685.].
Synergistic Photothermal-Chemotherapy of Hepatocellular Carcinoma and Cancer Stem Cells via in situ pH-Responsive Hydrogels.
Wu Y, Xu X, Zhu Z … +2 more , Du F, Zheng G
Int J Nanomedicine · 2026 · PMID 42199659 · Full text
PURPOSE: Monotherapy with photothermal therapy (PTT) hardly achieves durable and significant antitumor efficacy. To further improve the therapeutic effect against tumors, in this study, the chemotherapeutic agent thiorid...
PURPOSE: Monotherapy with photothermal therapy (PTT) hardly achieves durable and significant antitumor efficacy. To further improve the therapeutic effect against tumors, in this study, the chemotherapeutic agent thioridazine (THZ) was loaded into a gel network formed by the Schiff base cross-linking of amino-functionalized graphene quantum dots (NH-GQDs) and oxidized dextran. A pH-responsive injectable carbon dot composite hydrogel delivery system (NTD@Gel) with dual effects of photothermal therapy and chemotherapy was thereby constructed. METHODS: The techniques including HRTEM, XPS, FTIR, SEM and rheological tests were employed to verify the successful fabrication of NTD@Gel and characterize its physicochemical properties. In vitro and in vivo experiments were conducted to comprehensively evaluate the antitumor efficacy and biosafety of this hydrogel. RESULTS: NTD@Gel exhibited excellent photothermal conversion performance and biocompatibility, and enabled the rapid and sustained release of THZ in the acidic microenvironment. In vitro experiments confirmed that NTD@Gel could synergistically kill Hep1-6 hepatocellular carcinoma cells through photothermal ablation and THZ-induced oxidative damage, and inhibited the oncogenic Akt/Stat3 signaling pathway activation. In vivo experiments demonstrated that NTD@Gel combined with near-infrared laser irradiation significantly inhibited tumor growth, reduced CD133 and CD326 expression on tumor cells, effectively prolonged the survival time of tumor-bearing mice, and caused no obvious pathological damage in the major organs of mice. CONCLUSION: NTD@Gel can significantly enhance the therapeutic efficacy against hepatocellular carcinoma and reduce the risk of metastasis and recurrence through the synergistic effect of photothermal therapy and chemotherapy.
Nanoplatforms-Enhanced High-Intensity Focused Ultrasound for Cancer Immunotherapy.
Zhang Y, Li Y, He C … +2 more , Zhang X, Huang Y
Int J Nanomedicine · 2026 · PMID 42199658 · Full text
High-intensity focused ultrasound (HIFU) is a non-invasive tumor therapy capable of activating anti-tumor immunity through the induction of immunogenic cell death. However, its therapeutic efficacy is constrained by seve...
High-intensity focused ultrasound (HIFU) is a non-invasive tumor therapy capable of activating anti-tumor immunity through the induction of immunogenic cell death. However, its therapeutic efficacy is constrained by several limitations, including energy attenuation, incomplete ablation, and the exacerbation of the immunosuppressive tumor microenvironment. Recently, a variety of nanoplatforms have been engineered as potent enhancers for HIFU, primarily including perfluorocarbons, metal-organic frameworks, and polymer-based nanomaterials. These nanoplatforms synergistically enhance both the physical destruction and immune activation efficacy of HIFU through mechanisms such as intensifying cavitation or thermal effects, functioning as smart drug depots for responsive drug release, or acting as nanomotors to facilitate deep tissue penetration. This review systematically summarizes the latest strategies and synergistic mechanisms by which these nanoplatforms augment HIFU-based immunotherapy, with a focus on comparing their differences in HIFU-enhancing mechanisms, immunomodulatory methods, and major anti-tumor outcomes. Furthermore, we critically analyze their respective advantages and limitations, and discuss the current challenges and future directions.
Transferrin-Functionalized Conjugated Polymer Nanoparticles for Enhanced Photodynamic Therapy of Glioblastoma.
Caverzan MD, Cesca BA, Palacios RE … +2 more , Chesta CA, Ibarra LE
Int J Nanomedicine · 2026 · PMID 42199657 · Full text
PURPOSE: Glioblastoma (GBM) remains one of the most lethal primary brain tumors due to its highly infiltrative nature, pronounced intratumoral heterogeneity, and the restrictive blood-brain barrier (BBB), which severely...
PURPOSE: Glioblastoma (GBM) remains one of the most lethal primary brain tumors due to its highly infiltrative nature, pronounced intratumoral heterogeneity, and the restrictive blood-brain barrier (BBB), which severely limit the efficacy of conventional therapies. Photodynamic therapy (PDT) offers a spatially and temporally controllable treatment modality; however, its clinical translation for GBM is hindered by insufficient tumor selectivity and suboptimal photosensitizer delivery to intracranial lesions. The purpose of this study was to develop and preclinically evaluate transferrin-functionalized conjugated polymer nanoparticles (CPNs) as a receptor-targeted nanoplatform to enhance BBB traversal, tumor cell uptake, and photodynamic therapeutic efficacy in GBM. METHODS: F8BT-based CPNs doped with platinum(II) octaethylporphyrin (PtOEP) and stabilized with poly(styrene-co-maleic anhydride) (PSMA) were synthesized by controlled nanoprecipitation and covalently conjugated to holo-transferrin (holo-Tf) using EDC/NHS chemistry. Nanoparticles were characterized by dynamic light scattering, zeta potential, UV-visible and fluorescence spectroscopy, transmission electron microscopy, electrophoretic mobility, and protein quantification assays. Cellular uptake, receptor specificity, and photodynamic cytotoxicity were evaluated in GBM cell lines. Therapeutic efficacy was further assessed in an orthotopic U87MG-tdiRFP glioblastoma mouse model. RESULTS: Holo-Tf functionalization increased nanoparticle hydrodynamic diameter, reduced surface charge magnitude, and introduced a protein-specific absorbance feature, while preserving colloidal stability and optical properties. Protein quantification assays confirmed retention of more than 70% of the input holo-Tf. In vitro, holo-Tf CPNs showed significantly enhanced uptake in TfR-high U87MG cells compared with non-functionalized CPNs (42% vs 18% nanoparticle-positive cells at 1 h; gMFI 211 vs 73 at 4 h), which was reduced by excess free holo-Tf, indicating receptor-mediated uptake. PDT mediated by holo-Tf CPNs produced greater phototoxicity in vitro and, in vivo, reduced tumor fluorescence and prolonged survival relative to controls. CONCLUSION: Transferrin functionalization enhances receptor-directed delivery and PDT efficacy of conjugated polymer nanoparticles in GBM, supporting their further optimization and translational development.
Hollow CuSe/PDA/IR820 Composite Nanoparticles with pH Response for Multimodal Synergistic Treatment of Esophageal Cancer.
Ma F, Ji A, Ma B … +9 more , Yang P, Li J, Liao S, Yao H, Xie X, Wang Z, Shi L, Gao S, Hou X
Int J Nanomedicine · 2026 · PMID 42199656 · Full text
PURPOSE: Esophageal cancer (EC) ranks among the most prevalent and lethal malignancies worldwide, and conventional therapeutic modalities, including surgery, radiotherapy, and chemotherapy, are constrained by inherent li...
PURPOSE: Esophageal cancer (EC) ranks among the most prevalent and lethal malignancies worldwide, and conventional therapeutic modalities, including surgery, radiotherapy, and chemotherapy, are constrained by inherent limitations. Recent advances in nanomedicine have opened new avenues for EC treatment. To achieve efficient and precise tumor eradication, this study developed a pH-responsive composite nanoplatform featuring a hollow architecture to enable high-efficiency loading of photosensitizers and realize multimodal synergistic therapy against EC through the integration of photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT). METHODS: A pH-responsive CuSe/PDA/IR820 composite nanoplatform was constructed by coating hollow CuSe nanoparticles with polydopamine PDA and loading the near-infrared photosensitizer IR820. Morphology, crystalline phase, elemental composition, and surface chemistry were characterized by TEM, XRD, XPS, and FT-IR. Photothermal conversion efficiency was quantified under 808 nm laser irradiation. IR820 release kinetics were monitored under different pH conditions of 5.0, 6.0, and 7.0 to assess pH-responsive behavior. In vitro studies on KYSE-150 EC cells included viability by CCK-8 assay, apoptosis by flow cytometry, ROS generation by DCFH-DA probe, mitochondrial membrane potential by JC-1 staining, and cellular uptake analysis. In vivo antitumor efficacy and biosafety were evaluated in an AKR tumor-bearing C57BL/6J mouse model via intratumoral injection and 808 nm laser irradiation, followed by tumor volume measurement, histopathological analysis with H&E, Ki-67, and TUNEL staining, and systemic toxicity assessment. RESULTS: The hollow CuSe/PDA/IR820 nanoparticles exhibited a uniform size of approximately 164 nm, excellent colloidal stability, and a high photothermal conversion efficiency of 44.56% under 808 nm laser irradiation. IR820 release displayed pronounced pH sensitivity, with a cumulative release of 23.07% at pH 5.0 within 30 minutes. In vitro, the nanoplatform combined with laser irradiation reduced KYSE-150 cell viability to 1.2% at 100 μg/mL, with an IC50 value of 18.74 μg/mL, induced 28.57% apoptosis, elevated intracellular ROS levels, decreased mitochondrial membrane potential, and depleted glutathione to 335 μmol/gprot. In vivo fluorescence imaging confirmed effective tumor accumulation via the EPR effect, with peak signal at 24 hours post-injection. Combined PTT/PDT/CDT treatment significantly suppressed tumor growth, reducing final tumor volume to 17.8% of the control group, and induced extensive apoptosis and necrosis in tumor tissues. Systemic biosafety evaluations revealed no significant hematological or histopathological abnormalities. CONCLUSION: Hollow CuSe/PDA/IR820 composite nanoparticles loaded with IR820 were successfully fabricated and demonstrated remarkable advantages in multimodal combination therapy against EC.
Size-Optimized LDH Nanoplatelet-Reinforced GelMA Hydrogels Orchestrate Osteoimmunomodulation for Critical-Sized Bone Defect Repair.
Zhao M, Yang N, Han Y … +6 more , Huang J, Xu J, Wu W, Gao X, Ying B, Jia S
Int J Nanomedicine · 2026 · PMID 42199655 · Full text
BACKGROUND: Large bone defects remain difficult to heal because effective regeneration requires not only osteogenesis but also a favorable immune microenvironment. Layered double hydroxides (LDHs) are promising bioactive...
BACKGROUND: Large bone defects remain difficult to heal because effective regeneration requires not only osteogenesis but also a favorable immune microenvironment. Layered double hydroxides (LDHs) are promising bioactive nanomaterials, yet the influence of nanoparticle size on osteoimmunomodulation and bone repair remains insufficiently understood. METHODS: MgAl-LDH nanoparticles with lateral sizes of 50 and 100 nm were synthesized and characterized, then evaluated for cellular uptake, cytocompatibility, macrophage polarization, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). LDH nanoparticles were further incorporated into GelMA hydrogels and tested in a murine critical-sized calvarial defect model. Transcriptomic profiling was performed to explore the underlying regenerative mechanisms. Data distribution was assessed using the Shapiro-Wilk test, and normally distributed datasets were analyzed by one-way ANOVA followed by Tukey's post hoc test. RESULTS: Both LDH formulations showed well-defined hexagonal morphology, good colloidal stability, and negligible cytotoxicity. Compared with 100 nm LDH, 50 nm LDH exhibited greater cellular internalization and more effectively shifted macrophages from a pro-inflammatory to a pro-regenerative phenotype (p < 0.05). In BMSCs, LDH treatment enhanced alkaline phosphatase activity, matrix mineralization, and osteogenic gene expression, with the 50 nm group showing the strongest effects (p < 0.05). In vivo, GelMA-LDH hydrogels significantly promoted bone regeneration relative to GelMA alone, with superior performance observed for the 50 nm LDH group (p < 0.05). RNA sequencing and qPCR analyses identified a regeneration-associated molecular signature that was consistent with activation of Wnt/β-catenin-associated signaling together with attenuation of NF-κB-related inflammatory pathways. CONCLUSION: Size-optimized MgAl-LDH nanoplatelets, particularly the 50 nm formulation, act as an effective nano-bio interface to couple immunomodulation with osteogenesis. GelMA-LDH nanocomposite hydrogels therefore represent a promising nanomedicine strategy for critical-sized bone defect repair, although further mechanistic validation is still required.
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