JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2024
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IF 9.4
Jianying Ye,Jiang Yu,Mingming Zhao,Yingxi Zhang,Zhaomeng Wang,Shuo Li,Baoyue Zhang,Haolin Zhang,Tengfei Zhou,Yuhang Wang,Xin Li,Zhonggui He,Hongzhuo Liu,Yongjun Wang
Cancer immunotherapy has emerged as a potent treatment strategy by harnessing the host immune system to target cancer cells. However, challenges including low tumor vaccine immunogenicity and tumor heterogeneity hinder its clinical efficacy. To address these issues, we propose a novel nanoplatform integrating photothermal material gold nanorods (GNRs) with polyphenols for enhanced immunotherapy efficacy via photothermal therapy. Polyphenols, natural compounds with phenolic hydroxyl groups, are known for their ability to bind tightly to various molecules, making them ideal for antigen capture. We synthesized GNRs modified with polyphenols (GNR-PA and GNR-GA) and demonstrated their ability to induce immunogenic cell death upon laser irradiation, releasing tumor-associated antigens (TAAs). The surface polyphenols on GNRs effectively captured released TAAs to shield them from clearance. In vivo studies confirmed increased accumulation of GNR-GA in lymph nodes and enhanced dendritic cell maturation, leading to promoted effector T cell infiltration into tumors. Furthermore, treatment combined with PD-1/PD-L1 pathway blockade demonstrated potent tumor regression and systemic immunotherapy efficacy. Our findings highlight the potential of this photothermal nanoplatform as a promising strategy to overcome the limitations of current cancer immunotherapy approaches and improve therapeutic outcomes.
研究领域:
癌症免疫疗法
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纳米技术
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光热疗法
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2024
·
IF 3.7
Lida Feng,Guixiao Huang,Qifang Lei,Mingkang Liang,Dashi Deng,Xiaocen Liu,Chenfan Kong,Chenchen Li,Xiyang Tan,Guangzhi Li,Song Wu
Intravesical instillation-based immunotherapy for bladder-preservation of bladder cancer (BCa) treatment has not been explored. In the current study, two irrigated nano-formulations of immunological adjuvant-fluorinated chitosan (FCS) and therapeutic antibody-FCS are developed for synergistic immunotherapy against BCa. In this system, FCS is employed as a transepithelial carrier to assemble with bovine serum albumin (BSA)-flubendazole (FBZ) complex and anti-PD-1 (αPD-1) respectively, to facilitate efficient transepithelial delivery of intravesical FBZ-BSA and αPD-1 though transiently regulating the distribution of tight junction proteins on bladder epithelium. In addition, the FBZ–BSA complex exhibits tumor microenvironment-responsive charge reversal and BSA carrier-broken effects to drive tumor-targeted dissociation and drug release of FBZ–BSA/FCS. Moreover, FBZ not only promotes apoptosis and inhibits glycolysis in cancer cells but also displays adjuvant properties to activate potent immune responses through IL-12/IFN-γ pathway. Interestingly, combined perfusion of FBZ–BSA/FCS and αPD-1/FCS nano-formulations can significantly activate the tumor immune microenvironment, especially CD8 + T cell infiltration and αPD-1 sensitivity, and finally remarkably inhibit tumor growth in the mouse orthotopic BCa model. Thus, this study presents a novel intravesical delivery platform for ICB antibodies and a smart adjuvant system to achieve potent synergy immunotherapy, which is promising for bladder-preserving treatment against BCa.
研究领域:
药学
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癌症研究
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免疫学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2024
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IF 15.8
Qian Cheng,Xiaolei Shi,Yuzhe Chen,Qilin Li,Jiawei Wang,Heli Li,Lin Wang,Zheng Wang
Abnormal tumor microenvironment (TME) imposes barriers to nanomedicine penetration into tumors and evolves tumor-supportive nature to provide tumor cell protection, seriously weakening the action of antitumor nanomedicines and posing significant challenges to their development. Here, we engineer a TME-activatable size-switchable core–satellite nanosystem (Mn-TI-Ag@HA) capable of increasing the effective dose of therapeutic agents in deep-seated tumors while reversing tumor-supportive microenvironment for augmenting immuno/metal-ion therapy. When activated by TME, the nanosystem disintegrates, allowing ultrasmall-sized Ag nanoparticles to become unbound and penetrate deep into solid tumors. Simultaneously, the nanosystem produces O2 and releases TGF-β inhibitors in situ to drive macrophage M2-to-M1 polarization, increasing intratumoral H2O2 concentration, and ultimately augmenting metal-ion therapy by accelerating hypertoxic Ag+ production. The nanosystem can overcome multiple obstacles that aid in tumor resistance to nanomedicine, demonstrating effective tumor penetration, TME regulation, and tumor inhibition effects. It can provoke long-term immunological memory effects against tumor rechallenge when combined with immune checkpoint inhibitor anti-PD-1. This work provides a paradigm for designing efficient antitumor nanomedicines.
研究领域:
纳米技术
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癌症生物学
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免疫疗法
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药物递送系统
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肿瘤微环境
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-18
·
IF 14.7
Tang Xudong,Shang Yangyang,Yang Hong,Song Yalan,Li Shan,Qin Yusi,Song Jingyi,Chen Kang,Liu Yang,Zhang Dinglin,Chen Lei
The PD-1/PD-L1 pathway in mucosal immunity is currently actively explored and considered as a target for inflammatory bowel disease (IBD) treatment. However, systemic PD-L1 administration may cause unpredictable adverse effects due to immunosuppression. Here we show that reactive oxygen species (ROS)-responsive nanoparticles enhance the efficacy and safety of PD-L1 in a mouse colitis model. The nanoparticles control the accumulation and release of PD-L1 fused to Fc (PD-L1-Fc) at inflammatory sites in the colon. The nanotherapeutics shows superiority in alleviating inflammatory symptoms over systemic PD-L1-Fc administration and mitigates the adverse effects of PD-L1-Fc administration. The nanoparticles-formulated PD-L1-Fc affects production of proinflammatory and anti-inflammatory cytokines, attenuates the infiltration of macrophages, neutrophils, and dendritic cells, increases the frequencies of Treg, Th1 and Tfh cells, reshapes the gut microbiota composition; and increases short-chain fatty acid production. In summary, PD-L1-Fc-decorated nanoparticles may provide an effective and safe strategy for the targeted treatment of IBD.
研究领域:
药理学
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免疫学
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纳米技术
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
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IF 15.8
Jing Zhang,Yuanwei Pan,Lujie Liu,Yangtao Xu,Chenchen Zhao,Wei Liu,Lang Rao
Immune checkpoint blockade (ICB) has brought tremendous clinical progress, but its therapeutic outcome can be limited due to insufficient activation of dendritic cells (DCs) and insufficient infiltration of cytotoxic T lymphocytes (CTLs). Evoking immunogenic cell death (ICD) is one promising strategy to promote DC maturation and elicit T-cell immunity, whereas low levels of ICD induction of solid tumors restrict durable antitumor efficacy. Herein, we report a genetically edited cell membrane-coated cascade nanozyme (gCM@MnAu) for enhanced cancer immunotherapy by inducing ICD and activating the stimulator of the interferon genes (STING) pathway. In the tumor microenvironment (TME), the gCM@MnAu initiates a cascade reaction and generates abundant cytotoxic hydroxyl (•OH), resulting in improved chemodynamic therapy (CDT) and boosted ICD activation. In addition, released Mn2+ during the cascade reaction activates the STING pathway and further promotes the DC maturation. More importantly, activated immunogenicity in the TME significantly improves gCM-mediated PD-1/PD-L1 checkpoint blockade therapy by eliciting systemic antitumor responses. In breast cancer subcutaneous and lung metastasis models, the gCM@MnAu showed synergistically enhanced therapeutic effects and significantly prolonged the survival of mice. This work develops a genetically edited nanozyme-based therapeutic strategy to improve DC-mediated cross-priming of T cells against poorly immunogenic solid tumors.
研究领域:
癌症研究
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免疫学
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纳米技术
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2025
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IF 5.9
Xin Wei,Yuyan Guo,Jianyuan Lei,Na Chen
Introduction Microsatellite stable colorectal cancer (MSS-CRC) is referred to as an immune desert-type tumor. Emerging studies have demonstrated that inhibition of the Wnt/β-catenin pathway can enhance the anti-tumor immune response. This research focuses on synthesizing the human serum albumin (HSA) -based Wnt inhibitor GHSACA and assessing its internalization pathway and therapeutic effectiveness in conjunction with PD-1 antibody for treating MSS-CRC. Methods Glucosamine was covalently conjugated to HSA via EDC/NHS activation to generate GHSA, which was subsequently coupled with carnosic acid (CA) -Wnt pathway inhibitor, to synthesize GHSACA. For in vitro studies, LOX1- and CD44- deficient MC38 and CT26 colon cancer cell lines, validated by RT-qPCR, were used to investigate the cellular uptake mechanism and macropinocytic activity of GHSACA using flow cytometry. The effectiveness of GHSACA in targeting tumors in vivo was assessed in CT26 tumor-bearing BALB/c mice via fluorescence imaging. Therapeutic efficacy was assessed in MSS-CRC patient-derived xenograft (PDX). Results RT-qPCR confirmed efficient knockdown of LOX1 and CD44 in both MC38 and CT26 cell lines. Cellular uptake assay demonstrated that GHSACA internalization is predominantly mediated by the LOX1-dependent macropinocytosis pathway. In vivo fluorescence imaging revealed sustained accumulation of GHSACA in tumor and rapid clearance from normal organs. In the PDX model, GHSACA monotherapy significantly suppressed tumor growth (TGI = 59.3%). The combination with PD-1 antibody (G&P group) resulted in further enhancement of antitumor efficacy (TGI = 87.9%). TUNEL assays showed the most pronounced induction of tumor cell apoptosis in the G&P group. Immunohistochemical analysis demonstrated that GHSACA suppressed the Wnt/β-catenin signaling cascades, alongside with lower Ki67 expression. The G&P combination increased PD-L1 expression and significantly boosted Granzyme B-positive cytotoxic immune responses. Immunofluorescence double staining showed the highest infiltration of CD3 + /CD8 + cytotoxic T lymphocytes of the G&P group, with a concurrent decrease in CD4 + /CD25 + regulatory T cells. GHSACA was found to have favorable systemic biocompatibility and safety. Discussion GHSACA achieves efficient targeted cellular internalization via a macropinocytosis pathway regulated by the LOX1 receptor rather than the CD44 receptor, simultaneously inhibiting the Wnt/β-catenin signaling while activating anti-tumor immune responses. It provides a highly promising translational therapeutic approach for overcoming immune resistance in MSS-CRC.
研究领域:
肿瘤学
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纳米医学
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免疫治疗
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分子生物学
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药物递送
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癌症免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
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IF 13.2
Xietao Ye,Yeyang Sun,Lin Yang,Chen Chen,Shihao Li,Shuo Dong,Xiaoying Qin,Xiaoqi Li,Congyan Liu,Jiege Huo,Yuping Liu,Yan Chen
The low infiltration and insufficient tumor recognition of cytotoxic-T-lymphocytes (CTLs) are the two primary reasons for the low objective response rate of programmed death-1 protein (PD-1) inhibitors in treating microsatellite-stable colorectal-cancer (MSS-CRC). Ginsenoside Rg1 (Rg1) and atractylenolide-I (Att) can promote CTLs infiltration and recognition of CTLs by facilitating dendritic cells (DCs) maturation and upregulating tumor MHC-I expression, respectively, and the combination of two drugs is expected to improve the efficacy of PD-1 inhibitors. However, due to their poor water solubility and limited tumor targeting, the intratumoral delivery of both drugs faces challenges. Our previously reported a tumor-apoptotic-body-membrane (Ab) modified zeolitic-imidazolate-framework (ZIF) for co-delivering Rg1 and Att (Ab@Rg1/Att-ZIF). It could be transported by monocytes/macrophages into the deep tumor regions, however, partial formulations would be degraded by intracellular lysosomes. To overcome this, we innovatively incorporated inulin into Ab@Rg1/Att-ZIF, constructing an Ab/In@Rg1/Att-ZIF delivery system. By virtue of the Ab and inulin coating on its surface, the system could be specifically phagocytosed by monocytes/macrophages while maintaining stability in the lysosomal. Furthermore, after being transported to CRC tissues, inulin of the Ab/In@Rg1/Att-ZIF is enzymatically degraded by enzymes secreted by intratumoral bacteria, releasing Rg1 and Att to promote DCs maturation and upregulate tumor MHC-I expression, respectively. Ab/In@Rg1/Att-ZIF significantly inhibits tumor growth by enhancing CTLs infiltration and recognition, synergizing with PD-1 inhibitors to achieve a tumor suppression rate of ≈80 %, which is markedly higher than the combined efficacy of Ab@Rg1/Att-ZIF. This study provides new insights for the immunotherapy of MSS-CRC and the intratumoral co-delivery of drugs.
研究领域:
免疫治疗
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纳米医学
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药物递送
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肿瘤学
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肿瘤微环境
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癌症免疫学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2022
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IF 9.965
Guanghui Hou,Junmin Qian,Min Guo,Weijun Xu,Jinlei Wang,Yaping Wang,Aili Suo
Immune checkpoint blockade (ICB)-based immunotherapy is a revolutionary therapeutic strategy for hepatocellular carcinoma (HCC). However, tumor immune tolerance and escape severely restrict the therapeutic efficacy of ICB therapy. It is urgent to explore new strategies to potentiate ICB therapy in HCC. Herein, we developed manganese oxide-crosslinked bovine albumin/hyaluronic acid nanoparticles (BHM) by an innovative hydrazide-manganese coordination and desolvation process. Successive loading of doxorubicin (DOX) and indocyanine green (ICG) was achieved via hydrazone linkage and electrostatic interactions, respectively, obtaining DOX/ICG-coloaded BHM nanoplatform (abbreviated as BHMDI). The BHMDI nanoplatform exhibited a high drug content (>46%) and pH/reduction dual-responsive drug release behavior. The nanoplatform could efficiently alleviate tumor hypoxia by catalytic decomposition of intracellular H 2 O 2 to O 2 and significantly improve BHMDI-based photodynamic chemotherapy efficacy. The BHMDI nanoplatform downregulated the proportion of alternatively activated (M2) macrophages in tumors and simultaneously induced immunogenic death of HCC cells, thus promoting the maturation of dendritic cells and ensuing priming of CD4 + and CD8 + T cells . Importantly, programmed death-1 (PD-1) blockade in combination with BHMDI nanoplatform not only eradicated primary tumors but inhibited tumor recurrence, abscopal tumor growth and lung metastasis of HCC by triggering robust systemic antitumor immunity. This work proved the feasibility of BHMDI-based photodynamic chemotherapy for potentiating PD-1 blockade immunotherapy by reversing hypoxic and immunosuppressive tumor microenvironment.
研究领域:
肿瘤学
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纳米技术
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免疫学
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药学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
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IF 12.8
Jinming He,Xijiao Ren,Qiqi Zhang,Shuang Wang,Zhongjun Li,Kaiyong Cai,Menghuan Li,Yan Hu,Qian Ran,Zhong Luo
The insufficient activation and impaired effector functions of T cells in the immunosuppressive tumor microenvironment (TME) substantially reduces the immunostimulatory effects of radiotherapy. Herein, a multifunctional nanoradiosensitizer is established by integrating molecularly engineered aptamer precursors into cisplatin-loaded liposomes for enhancing radio-immunotherapy of solid tumors. Exposure to ionizing radiation (IR) following the nanoradiosensitizer treatment would induce pronounced immunogenic death (ICD) of tumor cells through cisplatin-mediated radiosensitization while also trigger the detachment of the aptamer precursors, which further self-assemble into PD-L1/PD-1-bispecific aptamer-based T cell engagers (CA) through the bridging effect of tumor-derived ATP to direct T cell binding onto tumor cells in the post-IR TME in a spatial-temporally programmable manner. The CA-mediated post-IR tumor-T cell engagement could override the immunosuppressive barriers in TME and enhance T cell-mediated recognition and elimination of tumor cells while minimizing systemic toxicities. Overall, this work offers an innovative approach to enhance the radio-immunotherapeutic efficacy in the clinics.
研究领域:
癌症治疗
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放射肿瘤学
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免疫疗法
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纳米技术
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分子生物学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-19
·
IF 14.7
Zhang Weiqi,Zeng Yinghua,Xiao Qiuqun,Wu Yuanyuan,Liu Jiale,Wang Haocheng,Luo Yuting,Zhan Jie,Liao Ning,Cai Yanbin
Targeted immunomodulation for reactivating innate cells, especially macrophages, holds great promise to complement current adaptive immunotherapy. Nevertheless, there is still a lack of high-performance therapeutics for blocking macrophage phagocytosis checkpoint inhibitors in solid tumors. Herein, a peptide-antibody combo-supramolecular in situ assembled CD47 and CD24 bi-target inhibitor (PAC-SABI) is described, which undergoes biomimetic surface propagation on cancer cell membranes through ligand-receptor binding and enzyme-triggered reactions. By simultaneously blocking CD47 and CD24 signaling, PAC-SABI enhances the phagocytic ability of macrophages in vitro and in vivo, promoting anti-tumor responses in breast and pancreatic cancer mouse models. Moreover, building on the foundation of PAC-SABI-induced macrophage repolarization and increased CD8 + T cell tumor infiltration, sequential anti-PD-1 therapy further suppresses 4T1 tumor progression, prolonging survival rate. The in vivo construction of PAC-SABI-based nano-architectonics provides an efficient platform for bridging innate and adaptive immunity to maximize therapeutic potency.
研究领域:
免疫学
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肿瘤学
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生物技术
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2018
·
IF 3.466
Xian Tang,Jingdong Rao,Sheng Yin,Jiaojie Wei,Chunyu Xia,Man Li,Ling Mei,Zhirong Zhang,Qin He
The Cancer-Immunity Cycle is a series of anticancer immune responses initiated and allowed to proceed and expand iteratively. Paclitaxel (PTX) is a classic chemotherapeutic agent, which could induce immunogenic cell death (ICD) to trigger the Cancer-Immunity Cycle. However, the Cycle is severely impaired by tumor cell immunosuppression of host T cell antitumor activity through the programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) (PD-1/PD-L1) immune checkpoint pathway. Here, we demonstrated that PTX mediated the Cancer-Immunity Cycle could be enhanced by PD-L1 knockdown (KD) and followed mTOR pathway inhibition in tumor cells. PD-L1 siRNA (siP) and the hydrophobic chemotherapy drug PTX were co-delivered with a rationally designed hybrid micelle (HM). We showed clear evidence that the HM-siP/PTX is capable of delivering siP and PTX simultaneously to the B16F10 cells both in vitro and in vivo . We demonstrated that HM-PTX/siP reduced the expression of PD-L1 and p-S6K (a marker of mTOR pathway activation) both in vitro and in melanoma-bearing mice and attenuated synergistically tumor growth by chemical toxicity , promoting cytotoxic T-cell immunity and suppressing the mTOR pathway.
研究领域:
肿瘤学
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免疫治疗
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药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）