Advanced Healthcare Materials
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2026
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IF 11
Quan Zhou,Imran Ibrahim Shaikh,Jianfeng Wang,Tongjun Li,Xinrong Wang,Shekhar Singh,Ayesha Younas,Yaru Shi,Kwonseop Kim,Shuanghu Wang,Jian Xiao
Spinal cord injury (SCI) remains a major clinical challenge because the inflammatory and oxidative microenvironment drives secondary tissue damage. Although mollugin (Mol) possesses anti-inflammatory, antioxidant, and neuroprotective activities, its therapeutic application is limited by poor water solubility and rapid clearance. In this study, we developed a RVG-modified liposomal nanoplatform for targeted delivery of mollugin (Mol@Lip-RVG) as a novel therapeutic strategy for SCI. The Mol@Lip-RVG nanoplatform exhibited excellent biocompatibility, favorable physicochemical characteristics, and sustained drug release profile. In vitro studies demonstrated that Mol@Lip-RVG effectively downregulated pro-inflammatory mediators, promoted microglial polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype, and significantly reduced reactive oxygen species production. In SCI mice, the RVG modification enabled efficient crossing of the BSCB and selective accumulation at the injury site through specific binding to nAChRs. This targeted delivery resulted in enhanced neuro-preservation and substantial improvement in motor function recovery, achieved through dual modulation of microglial reprogramming and attenuation of oxidative stress. Mechanistically, we demonstrated that Mol@Lip-RVG exerts its therapeutic effects is associated with inhibition of the NF-κB signaling pathway, thereby suppressing neuroinflammation. Collectively, these findings establish the Mol@Lip-RVG nanoplatform as a promising targeted therapeutic approach that addresses both the delivery challenges and complex pathophysiology of spinal cord injury.
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Pharmaceutics
·
2026
·Vol. 18
·期 7
·872
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IF 6.9
Weinan Li,Sisi Yan,Yingying Gao,Yuhan Fu,Yutong Mei,Yanhong Wang,Zhixin Yang
Background: The highly heterogeneous and dynamically evolving tumor microenvironment leads to the development of drug resistance and recurrence in traditional therapies. Although immunotherapy demonstrates unique advantages, its clinical utility remains constrained by the suboptimal immunogenicity and the limited effect of monotherapy. Herein, a hybrid drug delivery system based on a spatiotemporal hierarchical controlled-release strategy was proposed to achieve dual immunotherapy with immune checkpoint blockade (ICB) and immunogenic cell death (ICD) to promote synergistic anti-tumor therapy.Methods: A liposome–micelle hybrid drug delivery system (RUT-RPP-LP) was constructed using a lipid bilayer composed of dioleoyl phosphatidylethanolamine/hemisuccinyl cholesterol to encapsulate rutin (RUT) and to form an inner cavity-encapsulated resveratrol micelle (RPP). RUT-RPP-LP was characterized, and its pH sensitivity and release behavior were investigated. Subsequently, a colon cancer tumor-bearing mouse model was constructed to evaluate the in vivo targeted anti-tumor effect and biological safety. On this basis, the combined mechanism of ICB and ICD was preliminarily explored.Results: RUT-RPP-LP possessed excellent formulation characteristics, stability, and biocompatibility, achieving graded controlled release of drugs via responding to the TME and lysosomal acidity, respectively. Obviously, RUT-RPP-LP could specifically target the tumor site, induce the occurrence of ICD, and simultaneously block the PD-1/PD-L1 immune checkpoint signaling pathway, thereby enhancing the function of T cells and inducing apoptosis of tumor cells.Conclusions: The RUT-RPP-LP based on the hierarchical controlled-release strategy exerted a spatiotemporally coordinated enhancement of anti-tumor immunity, and may provide a novel combinatorial approach to overcome the low response of immunotherapy in solid tumors.
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International Journal of Nanomedicine
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2026
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IF 8.7
Qing Zhang,Chenguang Liu,Sirui Wu,Nan Zhong,Junfeng Qiu,Wei Fu,Xujun You
Purpose: Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men, with current treatments often limited by drug resistance and systemic toxicity. Although traditional Chinese medicine components such as Astragaloside IV and polypeptide extract from scorpion venom (PESV) have demonstrated promising antitumor activity, their clinical translation is hampered by poor bioavailability and lack of tumor specificity. To address these limitations, we engineered an E3 aptamer-modified T cell-derived exosomal nanoplatform (EAPE) for the targeted co-delivery of Astragaloside IV and PESV in prostate cancer therapy.Methods: EAPE was constructed and characterized, and its targeting capability, biosafety, and therapeutic performance were evaluated in vitro and in vivo. In vitro, the antitumor efficacy was assessed by proliferation, migration and apoptosis assays, while the immunomodulatory effects were investigated using a co-culture system of LNCaP cells and T lymphocytes. In vivo, the antitumor efficacy and immune activation were examined in prostate cancer xenograft mouse model, with tumor growth inhibition, apoptosis and immune responses measured.Results: EAPE demonstrated efficient tumor-targeting capability and favorable biosafety profiles both in vitro and in vivo. EAPE demonstrated superior therapeutic efficacy against PCa by inhibiting proliferation and migration of prostate cancer cells and inducing apoptosis, while suppressing immunosuppression and activating antitumor immune response.Conclusion: This study presents a biologically derived, targeted nanodelivery system that improves the delivery efficiency and therapeutic efficacy of Astragaloside IV and PESV. These findings support the potential of exosome-based nanoplatforms as promising strategies for enhancing the translational application of traditional Chinese medicine-derived therapeutics in prostate cancer.
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Drug Delivery and Translational Research
·
2026
·
IF 6.9
Zhang Rui Xue,Lu Weijia,Yan Xu,Deng Xudong,Wan Runrun,Song Zhejun,Liang Jiayan,Wang Xue-Ting,Cao Tingting,Chen Yan,Tam Paul K. H.
Precise dosing is critical for effective therapeutics, yet extensive enterohepatic metabolism poses a major barrier to many orally administered small-molecule drugs. Budesonide, a potent corticosteroid for treating enterohepatic inflammation, undergoes significant first-pass metabolism by cytochrome P450 3A abundantly expressed in the liver and intestine, resulting in variable efficacy and unpredictable toxicity. Rectal drug delivery offers an alternative route that can reduce first-pass metabolism. This work aimed to alter enterohepatic metabolism and clearance of budesonide using a rectal nanoparticles-hydrogel system for localized drug delivery. Budesonide was encapsulated into nanostructured lipid carrier (BD-LNP), which were then entrapped in a dynamic boronate ester crosslinked hydrogel (BD-LNP@Hydrogel). The hydrogel network exhibited thermal and mechanical stability, maintaining a drug depot post-injection, while BD-LNP was released in a controlled manner upon hydrogel degradation in simulated colonic fluid. BD-LNP@Hydrogel achieved a permeability coefficient > 1 × 10 –6 cm·s −1 across human intestinal epithelial monolayers, indicating completed absorption of budesonide. Compared to BD-LNP alone, BD-LNP@Hydrogel provided 4.3-fold higher nanoparticle exposure in the colonic lumen, enhancing intestinal uptake into deeper mucosal layer (e.g., lamina propria) over time. Pharmacokinetic analysis in mice revealed that rectal BD-LNP@Hydrogel markedly reduced formation of the budesonide metabolite 16α-hydroxyprednisolone compared to the oral route. Physiologically-based pharmacokinetic modeling confirmed preferential pharmacokinetics for rectal BD-LNP@Hydrogel over oral delivery, including up to 7.3-fold higher absorption rate constant, superior intestinal transport, and significantly reduced enterohepatic clearance of 16α-hydroxyprednisolone. These findings highlight the potential of nanoparticles-hydrogel systems for rectal delivery of drugs with extensive metabolism and provide mechanistic insight into achieving therapeutic precision via rectal delivery. Graphical
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CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Zihan Liu,Jiale Miao,Weiqing Ni,Ting Yang,Wenjing Dong,Junjiang Yu,Jiayu Yang,Yanhua Liu
An inflammation-responsive and endothelial cell-targeting R/HTM prodrug micelle nanotherapeutic system was developed for the effective management of rheumatoid arthritis. • R/HTM micelles realized dual modulation of neutrophil recruitment and survival via blocking P-selectin/PSGL-1-mediated adhesion cascade and ROS-triggered site-specific co-release of R-rsc and methylprednisolone. • R/HTM micelles comprehensively regulated the pathological synovial microenvironment, including clearing excess ROS, and inhibiting fibroblast-like synoviocyte invasion. • R/HTM micelles markedly mitigated synovial inflammation, cartilage damage and bone erosion in AIA rat models, holding broad translational potential for neutrophil-dominated inflammatory diseases. Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction, wherein aberrant neutrophil infiltration and prolonged neutrophil survival drive the amplification of inflammatory cascades. To disrupt these pathological processes, an inflammation-responsive, endothelial cell-targeting nanotherapeutic platform was constructed for dual modulation of neutrophil recruitment and survival. This system is composed of a heparin-thioketal-methylprednisolone (HTM) prodrug that self-assembles into HTM micelles, and it is loaded with the cyclin-dependent kinase inhibitor R-roscovitine (R-rsc) to produce R/HTM (R-rsc/HTM micelles). R/HTM micelle treatment effectively inhibited neutrophil recruitment in vitro by blocking P-selectin/PSGL-1-mediated adhesion to inflamed vascular endothelial cells. In the reactive oxygen species-enriched joint synovial microenvironment of the adjuvant-induced arthritis rat model, R/HTM micelle disassembly enabled co-release of R-rsc and methylprednisolone, which synergistically induced neutrophil apoptosis through Bcl-2 downregulation and Bax/Caspase-3 upregulation. This dual-phase strategy also suppressed neutrophil extracellular trap formation, reprogrammed macrophage polarization (toward an anti-inflammatory M2 phenotype), inhibited fibroblast-like synoviocyte invasion, and cleared excess ROS. Moreover, R/HTM treatment significantly alleviated joint inflammation, repaired cartilage damage, ameliorated bone erosion, and suppressed the levels of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α). Collectively, these findings establish R/HTM micelles as a potent nanotherapeutic system with a dual-phase mechanism that targets the key pathological checkpoints of neutrophil-mediated inflammation, offering a promising approach for the effective management of RA.
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Journal of Pharmaceutical Analysis
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2026
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IF 11.2
Guifeng Zhang,Hongjiang Li,Wei Zhang,Dan Pu,Longxing Wang,Xiaofei Han,Ju Wu
Mannan-oligosaccharides (MOS), as indigestible functional prebiotic, support intestinal health. Here, we engineered MOS to undergo linoleic acid (LA)-mediated self-assembly with quercetin, forming lipid bilayer nanoparticles (MOS-LA/LA-Q NPs). These nanoparticles achieved a high quercetin encapsulation efficiency (92.4%) and demonstrated superior stability in aqueous solution at 4 °C. The MOS outer layer effectively protected the quercetin core from gastrointestinal stress. Triggered by microbial enzymes, the system enabled a sustained quercetin release, up to 60% over 48 h, representing a novel microbe-specific delivery mechanism. In an Alzheimer’s disease (AD) mice models induced by AlCl 3 /D-galactose, MOS-LA/LA-Q NPs significantly enhanced gut microbiota diversity, restored gut microbiota balance, suppressed pathogenic bacteria, and regulated metabolites short-chain fatty acid (SCFA) and lactic acid levels. Compared with free quercetin, these nanoparticles (NPs) alleviated cognitive deficits, reduced inflammation and oxidative stress in both the colon and brain, improved gut-brain barrier integrity, and restored gut-brain function more significantly. Mechanistically, these effects were associated with modulation of the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathways, reducing tau phosphorylation and Aβ amyloid levels, thus demonstrating superior neuroprotection. This study proposes a novel strategy for addressing the complex pathology of AD through multi-target intervention, highlighting the potential of MOS-based NPs to enhance quercetin’s therapeutic efficacy.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2026
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IF 6
Yuanyuan Liu,Yuanyao Lin,Xuemei He
An ultrasound-responsive PLGA nanosystem co-encapsulating CXB, CAT, and PFP was developed. • Ultrasound triggered PFP phase transition and promoted on-demand CXB release from nanoparticles. • CAT retained catalytic activity and enabled oxygen generation, helping alleviate tumor hypoxia. • The nanosystem potentiated the antitumor activity of imatinib against GIST in vitro and in vivo. • Combined treatment increased apoptosis and suppressed migration and tumor growth in GIST. The therapeutic efficacy of imatinib (IM) in gastrointestinal stromal tumors (GISTs) is often limited by inadequate intratumoral drug accumulation and an abnormal tumor microenvironment. In this study, an ultrasound-responsive poly(lactic-co-glycolic acid) (PLGA) nanoparticle system, designated CXB/CAT@PFP-PLGA NPs, was developed for the co-delivery of celecoxib (CXB) and catalase (CAT) to enhance the antitumor efficacy of IM. The nanoparticles were characterized in terms of their physicochemical properties, ultrasound responsiveness, and oxygen-generating capability. Their ability to potentiate IM therapy was evaluated both in vitro and in vivo, while biodistribution and biosafety were assessed in vivo. The results showed that CXB/CAT@PFP-PLGA NPs exhibited a relatively uniform size distribution and successfully co-encapsulated CXB and CAT. Upon ultrasound irradiation, the nanoparticles underwent phase transition, thereby triggering drug release. In vitro, CXB/CAT@PFP-PLGA NPs enhanced the inhibitory effect of IM by reducing cell viability, promoting apoptosis, and inhibiting cell migration. In vivo, the nanosystem improved the antitumor efficacy of IM, accumulated at the tumor site, suppressed tumor growth, and showed no evident systemic toxicity. Collectively, these findings suggest that CXB/CAT@PFP-PLGA NPs may represent a promising strategy for enhancing IM therapy in GIST. Download: Download high-res image (89KB) Download: Download full-size image
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MICROCHIMICA ACTA
·
2026
·Vol. 193
·期 9
·634
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IF 5.4
Li Ce,Zeng Yutong,Wei Keyi,Li Xinyan,Wang Yan
Three exosome fluorescence-labeling workflows based on azide-functionalized cholesterol anchoring and copper-free click chemistry were systematically optimized and comparatively evaluated. A549 cell-derived exosomes were used as the primary model. By varying the sequence of azide introduction and fluorescent click reaction, one-step, two-step, and three-step protocols were compared. Under the tested conditions, the two-step protocol provided the most favorable overall balance among exosome recovery, fluorescence intensity normalized to exosome particle concentration, dye consumption, reaction volume, and operational simplicity. After labeling, the exosomes retained their typical morphology, particle size distribution, while the representative exosome-associated proteins CD63, CD81, and TSG101 remained detectable. The fluorescence intensity of the labeled exosomes showed a strong linear correlation with particle concentration, supporting its potential for rapid quantitative analysis. Cellular uptake experiments confirmed the feasibility of the labeled exosomes for in vitro imaging, and fluorescence remained detectable during the 24-h in vivo observation period. Overall, this study identifies an optimized two-step workflow for exosome fluorescence labeling and provides a practical approach for exosome visualization and tracking under the evaluated experimental conditions. Graphical abstract
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Research
·
2025
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IF 10.7
Chengjunyu Zhang,Sen Liu,Jianhui Zhang,Junlin Lu,Zehua Chen,Bolin Pan,Chu Liu,Ming Huang,Hengji Zhan,Hongjin Wang,Siting Chen,Kaiwen Jie,Baoqing He,Jingdie Wu,Ye Li,Haifeng Wang,Jing Zhao,Qiang Zhang,Xu Chen
Ferroptosis has promising potential for augmenting antitumor effects, but monotherapy with ferroptosis inducers in vivo has been reported to have limited efficacy in tumor management. The development of synergistic strategies with targeted capabilities is crucial for enhancing the antitumor efficacy of ferroptosis inducers. In this study, we designed and characterized a novel self-assembled nanomedicine by mixing ferrous ions (Fe 2+ ) and epigallocatechin gallate (EGCG) in a controllable manner and encapsulating the ferroptosis inducer RSL3, named Fe-EGCG@RSL3. This multifunctional nanomedicine effectively induces ferroptosis and growth inhibition in bladder cancer cells and patient-derived organoids. In vivo, Fe-EGCG@RSL3 was enriched in the subcutaneous tumors of allogenic and xenograft mouse models, thereby substantially overcoming RSL3 resistance. Intravesical instillation of Fe-EGCG@RSL3 controls orthotopic bladder tumor progression. Furthermore, nanomedicine potentiates the therapeutic effect of anti-programmed cell death protein 1 (PD1) immunotherapy by increasing the cytotoxicity of CD8 + T cells to cancer cells and modulating the proportions of both T-cell and myeloid cell subpopulations within the tumor immune microenvironment. Overall, Fe-EGCG@RSL3 has dual functions as a multifaceted nanomedicine that integrates ferroptosis induction with immunomodulation, offering a novel and clinically translatable strategy for bladder cancer therapy.
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Scientific Reports
·
2025
·Vol. 15
·期 1
·1-13
·
IF 3.9
Meng Zhuo-Nan,Chen Jian-Yuan,Yu Chong,Zheng Ai-hong,Reddy O. Sreekanth,Liu Kai-Yan,Su Yong-Rui,Zhang Shi-Tai,Wang Yin-Shuang,Gu Hang-Yu,Wang Fu-Wei,Xu Song-Cheng,Sun Li-Tao,Chen Bing-Chen,Lai Wing-Fu,Wu Guo-Qing,Zhang Da-Hong
Surgical resection of the tumor remains the preferred treatment for most solid tumors at an early stage, however, residual tumor cells after surgical resection poses a considerable obstacle in cancer treatment. Here, we developed a gel carrier using a cellulose-based gel-forming polymer (CT) combined with gelatin sponge (GS) to fill the resection cavity and delay postoperative residual tumor growth. The fabricated gel exhibited a porous nature along with gradual swelling and erosion over time. Curcumin (Cur) and apatinib (Apa) were loaded into CT gel (CT-CA), and a sustained release behavior was observed at pH 7.4 and 6.4 at 37 °C. The preclinical studies indicated that the mouse weight and tissue exhibited no apparent change after administration of the GS-CT compared with the control. The in vivo fluorescence images showed that GS-CT has the capability to regulate the release of Cur and Apa, facilitating the accumulation of these two agents at the surgical tumor site. Moreover, GS-CT loaded Cur and Apa (GS-CT-CA) delayed postoperative residual tumor growth in intraperitoneal and subcutaneous postoperative mouse models. These findings demonstrated that our gel carrier system significantly prevents postoperative residual tumor growth because of enhanced drug accumulation and sustained drug release at the tumor site.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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BIOMATERIALS
·
2025
·
IF 12.9
Zishan Zeng,Jingwen Jiang,Yue Sun,Wanzhen Li,Dong Zheng,Huanxin Lin,Chunshun Zhao
Helicobacter pylori ( H. pylori ) is considered as the major pathogenic factor related to multiple digestive diseases. However, the efficacy of first-line treatment containing antibiotics gradually declined. It is urgent to develop treatment with antibiotic reduction/abandonment to combat H. pylori . Based on our previous discovery that Cu(DTC) 2 exhibited stronger bactericidal effect than that of disulfiram or diethyldithiocarbamate (DTC), we constructed an antibiotic-free therapeutic strategy composed of DTC prodrug, Cu 2+ and shikonin (SK) to eliminate H. pylori . DTC was firstly modified with nitroaromatic moiety to acquire DTC prodrug (NTR-DTC), which was further encapsulated into Cu-SK@DOPA to construct nanoprodrug Cu-SK@NTR-DTC to achieve the triple masking of DTC, Cu 2+ and SK for the specificity therapeutics. Cu-SK@NTR-DTC could penetrate mucus layer and mainly detain in the bacteria infection area. In the presence of H. pylori , DTC was released from NTR-DTC to recover activity of copper chelation, and competitively bound Cu 2+ from Cu-SK to form Cu(DTC) 2 . The released SK possessed the bactericidal sensitization effect on Cu(DTC) 2 . The H. pylori -activable dissociation of Cu-SK@NTR-DTC, and the local release of Cu(DTC) 2 and SK seriously destructed the bacterial membranes integrity and induce H. pylori death, which provided a feasible strategy to address the clinical limitations of H. pylori clearance.
研究领域:
医学
·
药学
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ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Qinglian Hu,Xiaoyu Huang,Tong Wang,Zhuoting Lu,Dongchang Sun,Yuanxiang Jin
Bioengineered probiotics enable new opportunities to address abnormal cancer metabolism and suppressive immune–environment interactions for improved therapeutic susceptibility. Here, Escherichia coli Nissle 1917 (EcN) was constructed to convert ammonia into l-arginine continuously and was further modified with polydopamine (PDA) to form living biotherapeutic argEcN@P for enhanced colorectal cancer eradication. Benefiting from the movement of EcN, argEcN@P could colonize and penetrate deep in tumors through hypoxia targeting and increase the intratumoral l-arginine concentrations. Upon near-infrared light (NIR) irradiation, heating induced by PDA could ablate tumor cells efficiently and release tumor antigens, which induce immunogenic cell death (ICD). More interestingly, argEcN@P remarkably promotes differentiation into M1-like macrophages in tumor tissues, inhibiting primary, distant tumor growth by inducing potent adaptive antitumor immunity. More importantly, argEcN@P treatment efficiently prevented postoperative tumor recurrence by inducing long-term immune memory. Taken together, this platform based on bioengineered probiotics provides a promising strategy for tumor metabolic reprogramming sensitized photothermal immunotherapy in deep tumors.
研究领域:
肿瘤学
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微生物学
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免疫学
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