International Journal of Nanomedicine
·
2025
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IF 6.5
Li Gao,Li-Hua Yang,Fang-Cheng Jiang,Wang-Yang Ye,Xin Chen,Zhao-Ji Liu,Rong-Quan He,Wan-Ying Huang,Zhen-Bo Feng,Jin-Liang Kong,Ze-Feng Lai,Gang Chen
Background Although immune checkpoint blocking (ICB) therapeutic agents have significantly improved the survival for many cancer patients, the efficacy of ICB therapy for non-small cell lung cancer (NSCLC) patients remains limited. Combining ICB therapy with other strategies that is able to stimulate tumor immunogenicity or increase infiltration of T cells aroused great concern in cancer therapy.Results Herein, we constructed a kind of AuNP@NH2-PEG-SH/PD-L1 siRNA nanoparticle complex which showed prominent photothermal therapeutic (PTT) effects triggered by NIR laser and could efficiently deliver PD-L1 siRNA into NSCLC cells (knock-down efficiency were 75.8% and 83% in HCC827 and A549 cells). During the process of photothermal stimulation, discrepancies in heat shock protein expression were observed in NSCLC cells. Knocking down PD-L1 expression in NSCLC cells such as A549 and HCC827 cells activated the co-culturing Jurkat cells and enhanced their tumor-killing effect in vitro (cell inhibition rate was 62.65% for HCC827 cells and 57.03% for A549 cells). The gold nanoparticle complexes exhibited remarkable PTT effect for the engrafted NSCLC cells in zebrafish larvas. Furthermore, the nano complexes could promote the activation of the xenografted human peripheral blood mononuclear cells (PBMCs) and enhance the killing of the NSCLC cells in the larvas.Conclusion It is well known that gold nanoparticle is one of the several metal nanoparticles approved for clinical trial by American FDA. This work has demonstrated the outstanding PTT and immunotherapeutic effects of gold nanoparticle complexes on NSCLC, indicating great potential in clinical regiment of lung cancers.
研究领域:
肿瘤学
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免疫学
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生物医学工程
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分子生物学
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转化医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-22
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IF 12.6
Liu Yanhong,Gong Liming,Feng Jing,Xiao Congcong,Liu Chenfei,Chen Bohan,Chen Liqing,Jin Mingji,Guan Youyan,Gao Zhonggao,Huang Wei
Immune checkpoint inhibition (ICI) has become the mainstay of immunotherapy for the treatment of renal cell carcinoma (RCC). However, only a small portion of patients exhibit a positive response to PD-1/PD-L1 blockade therapy and the key reason is that RCC belongs to a vascular-rich tumor for promoting immunosuppression. Specifically, the dysfunctional tumor vasculature hinders effector T cell infiltration and induces immunosuppressive tumor microenvironment via the release of cytokine, which attenuates the therapeutic efficacy of ICI. Therefore, regulating abnormal tumor vasculature may be a promising strategy to overcome the immunosuppressive microenvironment and enhance ICI therapy. Here, we propose an NGR peptide-modified actively targeted liposome (Axi/siRNA PD−L1 @NGR-Lipo) to encapsulate the anti-angiogenic agents Axitinib and PD-L1 siRNA to promote tumor vasculature normalization and relieve immune evasion for enhanced anti-tumor immunotherapy. With NGR-mediated tumor homing and active targeting, Axi/siRNA PD−L1 @NGR-Lipo could act on tumor vascular endothelial cells to inhibit neo-angiogenesis, increase pericyte coverage and vascular perfusion, and normalize the structure and function of tumor blood vessels. Meanwhile, it also enhanced immune effector T cells and NK cells infiltration and reduced the proportion of immunosuppressive T cells including MDSC cells and Tregs, thus improving the tumor immunosuppressive microenvironment. Moreover, Axi/siRNA PD−L1 @NGR-Lipo reduced the expression of PD-L1 protein in tumor cells, restored the recognition and killing ability of cytotoxic T cells, and relieved immune evasion. As expected, Axi/siRNA PD−L1 @NGR-Lipo displayed superior anti-tumor and anti-metastatic efficacy in mice bearing RCC. Overall, this study demonstrated the important potential of regulating abnormal tumor vasculature to reshape the immunosuppressive microenvironment and boost ICI therapy, which represents a promising avenue for the synergistic anti-tumor with cancer immunotherapy. Graphical
研究领域:
肿瘤学
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免疫学
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药剂学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 19
·8998-9008
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IF 7.79
Xupeng Mu,Meng Zhang,Anhui Wei,Fei Yin,Yan Wang,Kebang Hu,Jinlan Jiang
Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy. PD-L1 siRNA can restore the immune anti-tumor activity of T cells by downregulating the level of PD-L1 on tumor cells, but the efficiency of PD-1/PD-L1 monotherapy is relatively low. Doxorubicin (DOX) can induce tumor cell apoptosis, and then increase the release of tumor antigen. But the expression of PD-L1 in tumor tissues treated with DOX will be enhanced adaptively. Therefore, DOX combination with PD-L1 siRNA can produce a good synergistic anti-tumor effect. In this study, stem cell membrane (SCM) camouflaged polydopamine nanoparticles carrying DOX and PD-L1 siRNA (PDA–DOX/siPD-L1@SCM) were constructed for targeting prostate cancer (PCa) bone metastases. PDA–DOX/siPD-L1@SCM NPs could effectively enhance blood retention and improve accumulation at tumor sites. In vitro and in vivo studies demonstrated that PDA–DOX/siPD-L1@SCM NPs showed excellent performance in synergistic chemoimmunotherapy for PCa bone metastases. Hence, this study provided an effective strategy for developing biomimetic multifunctional nanoparticles for PCa bone metastasis treatment.
研究领域:
癌症研究
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纳米技术
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药学
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免疫治疗
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DOI
PubMed
高影响因子
BIOMATERIALS
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2022
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IF 15.304
Yan Gao,Zilin Song,Li Jia,Yi Tang,Chengcheng Wang,Xiuli Zhao,Haiyang Hu,Dawei Chen,Mingxi Qiao
Despite the important role of reactive oxygen species (ROS) in battling cancer, ROS production with current approaches has been severely limited by the deficiency of oxy-substrates in tumor microenvironment . Herein, an atorvastatin (Ato)-catalytic self-amplified approach was utilized for sustainable ROS production and enhancing anti-tumor efficacy of PD-L1 silencing. A C 18 -pArg 8 -ss-pHis 10 lipopeptide based self-assembled nanoplexes was developed to co-encapsulate AMP-activated protein kinase (AMPK) activator of Ato and PD-L1 siRNA. Efficient delivery of payloads was achieved because of the acidic pH triggered the protonation of pHis 10 , disulfide-bond exposure for cleavage and subsequent cytosolic translocation. Ato was found to activate AMPK, boosting the highly restrained mitochondrial fatty acid oxidation (FAO) in cancer cells for ROS production. The ROS derived from FAO further activated AMPK, creating a positive-feedback mechanism of sustainable ROS production. The self-amplified ROS production from cellular mitochondrial FAO was maintained by the sufficient intracellular fatty acid substrates arising from the dysregulated lipid metabolism and Ato inhibited triglyceride synthesis in cancer cells. The excessive ROS level was found to successfully induce immunogenic cell death effect, boosting the anti-tumor efficacy of PD-L1 silencing. Overall, the Ato catalyzed self-amplified ROS production has been demonstrated as a promising alternative for cancer therapy.
研究领域:
癌症治疗
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药学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2022
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IF 10.383
Qing Hu,Jiayi Yao,Xiaoqin Wang,Yanfang Wang,Xiaoling Fu,Ju Ma,Han Lin,Jiaqi Xu,Longhua Shen,Xiangbin Yu
Chemoimmunotherapy can synergistically enhance the therapeutic effects and decrease the side effects by a combined method. However, the effective targeted codelivery of various chemotherapeutic agents and siRNAs remains challenging. Although nanomedicine-based chemoimmunotherapy has shown great potential in cancer treatment in recent years, further effort is needed to simplify the nanocarrier designs and maintain their effective functions. Here, we report a simple but robust multifunctional liposomal nanocarrier that contains a pH-sensitive liposome (LP) shell and a dendritic core for tumor-targeted codelivery of programmed cell death ligand 1 (PD-L1) siRNA and doxorubicin (DOX) (siPD-L1@PM/DOX/LPs). siPD-L1@PM/DOX/LPs had a suitable particle size and zeta potential, excellent stability in serum, and pH-sensitive drug release in vitro. They exhibited significant cell proliferation inhibition compared to free DOX and DOX-loaded LPs and could escape endosomes, effectively release siRNA into the cytoplasm of MCF-7 cells, and significantly reduce the PD-L1 expression on tumor cells. In vivo imaging confirmed high accumulation of siPD-L1@PM/DOX/LPs at the tumor site. More importantly, compared with siPD-L1@PM/LPs or DOX alone, siPD-L1@PM/DOX/LPs were more effective in inhibiting tumor growth and activating cytotoxic T cells in vivo. In conclusion, this nanocarrier may hold promise as a codelivery nanoplatform to improve the treatment of various solid tumors.
研究领域:
癌症研究
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药学
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纳米技术
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分子生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·Vol. 12
·期 17
·2300110
·
IF 10
Shuaiying Wu,Jianzhong Zhang,Jie Pan,Shuang Bai,Ziying Wang,Yulun Chen,Dazhuang Xu,Yibo An,Chao Liu,Chengchao Chu,Qixuan Dai,Lai Jiang,Zhixiang Lu,Gang Liu
It is an engaging program for tumor treatment that rationalizes the specific microenvironments, activation of suppressed immune system (immune resistance/escape reversion), and synergistic target therapy. Herein, a biomimetic nanoplatform that combines oxidative stress with genetic immunotherapy to strengthen the therapeutic efficacy is developed. Ru-TePt nanorods, small interfering RNA (PD-L1 siRNA), and biomimetic cellular membrane vesicles with the targeting ability to design a multifunctional Ru-TePt@siRNA-MVs system are rationally integrated. Notably, the Fenton-like activity significantly enhances Ru-TePt nanorods sonosensitization, thus provoking stronger oxidative stress to kill cells directly. Meanwhile, immunogenic cell death is triggered to secrete numerous cytokines and activate T cells. The effective catalase characteristics of Ru-TePt enable the in situ oxygen-producing pump to improve tumor oxygen level and coordinately strengthen the therapeutic effect of SDT followed. More importantly, anti-PD-L1-siRNA mediated immune checkpoint silence of the PD-L1 gene creates an environment conducive to activating cytotoxic T lymphocytes, synergistic with boosted reactive oxygen species-triggered antitumor immune response. The experimental results in vitro and in vivo reveal that the Ru-TePt@siRNA-MVs nanosystems can effectively activate the oxidative stress-triggered immune response and inhibit PD-1/PD-L1 axis-mediated immune resistance. Consequently, this orchestrated treatment paradigm provides valuable insights for developing potential oxidative stress and genetic immunotherapy.
研究领域:
肿瘤学
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纳米技术
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免疫治疗
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分子生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2026
·
IF 8.7
Jing Zhang,Xiaoqiang Kong,Xiangping Wu,Dongyun Tao,Xiang Li,Huimin Cheng
Introduction Triple-negative breast cancer (TNBC) is an aggressive malignancy with poor prognosis, and Fusobacterium nucleatum (Fn) colonization further aggravates tumor progression, immunosuppression and therapeutic resistance. Conventional monotherapies are limited by insufficient tumor targeting, rapid drug clearance and failure to reverse immune suppression. Here, we fabricated cRGD-modified nanoparticles (Ag@GQDs/QUE-siP-c-L) for co-delivery of AgNPs, quercetin (QUE) and PD-L1 siRNA (siP).Methods The morphology, particle size, surface metal elements, drug content and QUE entrapment efficiency of Ag@GQDs/QUE-siP-c-L were obtained using particle size analysis, SEM, inductively coupled plasma-optical emission spectrometry (ICP-OES) and HPLC. We further detected cellular uptake, in vitro drug release, cytotoxicity, intracellular reactive oxygen species level, PD-L1 gene silencing efficiency and in vitro anti-Fn activity. Pharmacokinetics and tissue distribution of Ag and QUE were analyzed by ICP-OES and LC-MS/MS, and in vivo antitumor efficacy and biosafety were tested in Fn-colonized orthotopic 4T1 tumor mice.Results Ag@GQDs/QUE-siP-c-L exhibited uniform spherical morphology (195.87± 15.96 nm) with high encapsulation of QUE. cRGD modification enhanced Ag/QUE cellular uptake in 4T1 cells, with pH-responsive release accelerated under tumor acidic conditions. The nanoparticles exhibited selective tumor cytotoxicity, induced oxidative stress, downregulated PD-L1 mRNA, and exerted potent anti-Fn activity in vitro. Pharmacokinetics revealed increased AUC0-t and reduced clearance compared with free drugs, and cRGD modification promoted tumor accumulation and retention of drugs. In vivo preliminary experiments proved the Ag@GQDs/QUE-siP-c-L formulation suppressed tumor growth with a tumor inhibition rate of 45%, and effectively modulated the tumor immune microenvironment: it increased tumor-infiltrating CD3⁺CD4⁺ T cells, reduced PD-L1⁺CD11c⁺ dendritic cells, and decreased the proportions of immunosuppressive Tregs and MDSCs. Hematoxylin-eosin staining and serum liver-kidney biochemistry confirmed no obvious systemic toxicity.Conclusion Ag@GQDs/QUE-siP-c-L serves as a multimodal nanoplatform for Fn-associated TNBC with combined in vitro antibacterial, gene silencing and in vivo antitumor immunomodulatory effects, showing great potential for future translational research.
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DOI
高影响因子
Biomaterials Advances
·
2022
·
IF 0
Zhiwei Li,Jiaqi Bu,Xinyu Zhu,Hao Zhou,Kaiqun Ren,Paul K. Chu,Limin Li,Xiang Hu,Xiaofeng Ding
Programmed cell death receptor ligand 1 (PD-L1)/PD-1 signaling has been exploited to design inhibitors that deliver promising clinical outcome albeit with limited efficacy. Herein, we prepare graphene oxide (GO)-PEI-PEG with low cytotoxicity and long stability and GO-PEI-PEG delivers PD-L1 siRNAs to hepatocellular carcinoma (HCC) cells by the endocytosis-lysosome pathway. The functional GO-PEI-PEG/PD-L1 siRNAs decrease PD-L1 and PD-1 abundance, increase pro-inflammation cytokine IFN-γ and TNF-α release, and improve the proliferation activity of Jurkat T cells. Since GO-PEI-PEG targets the mouse liver effectively, the intrahepatic tumors in C57BL/6 mice are treated with GO-PEI-PEG/Pd-l1 siRNAs via the tail vein, resulting in shrinkage of the HCC tumors and boosting the anti-tumor efficacy in combination with oral sorafenib. A single treatment improves the total CD3 + and cytotoxic CD8 + T cell infiltration in the HCC tumor tissues and even spleen and upregulates the expression of Perforin, Gzmb, Ifng, Il-1b and Tnfa in the tumors after the combined treatment. Both the single and combined treatments enhance reactive oxygen species (ROS) accumulation, and improved HCC ferroptosis. The results suggest that GO-PEI-PEG delivered PD-L1 siRNAs combined with oral sorafenib can activate the adaptive immunity and tumor ferroptosis and reveal an effective therapy to treat advanced HCC patients.
研究领域:
肿瘤学
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分子生物学
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免疫学
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药理学
✓ 已验证
DOI
PubMed
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Panpan Song,Bingjie Wang,Qi Pan,Tianze Jiang,Xiangyan Chen,Miao Zhang,Jiaojiao Tao,Xia Zhao
Programmed cell death-ligand 1 (PD-L1) small interfering RNA (siRNA) achieves tumor immunotherapy by restoring the immune response of T cells, but the efficacy of PD-1/PD-L1 monotherapy is relatively low. While immunogenic cell death (ICD) can improve the response of most tumors to anti-PD-L1 and enhance tumor immunotherapy. Herein, a targeting peptide GE11-functionalized dual-responsive carboxymethyl chitosan (CMCS) micelle (G-CMssOA) is developed for simultaneous delivery of PD-L1 siRNA and doxorubicin (DOX) in a complex form of DOX·PD-L1 siRNA (D&P). The complex-loaded micelles (G-CMssOA/D&P) have good physiological stability and pH/reduction responsiveness, and improve the intratumoral infiltration of CD4 + and CD8 + T cells, reduce Tregs (TGF-β), and increase the secretion of immune-stimulatory cytokine (TNF-α). The combination of DOX-induced ICD and PD-L1 siRNA-mediated immune escape inhibition significantly improves anti-tumor immune response and inhibits tumor growth. This complex delivery strategy provides a new approach for effectively delivering siRNA and enhancing anti-tumor immunotherapy.
研究领域:
药学
·
免疫学
·
癌症研究
·
纳米技术
✓ 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）