ADVANCED FUNCTIONAL MATERIALS
·
2021
·Vol. 31
·期 28
·2100437
·
IF 18.808
Tong Gao,Zipeng Zhang,Shuang Liang,Shunli Fu,Weiwei Mu,Li Guan,Yang Liu,Qihui Chu,Yuxiao Fang,Yongjun Liu,Na Zhang
Immune checkpoint therapy promotes cytotoxic T lymphocytes (CTLs) activity to eliminate tumors. Nevertheless, their effectiveness in solid tumors is limited by inadequate infiltration of CTLs and suppressive tumor microenvironment (TME). Herein, an anti-PD-1 antibody coupled chemo-photothermal integrated nanoplatform (A/Au@MSMs-P) is proposed to reshape antitumor immunity against cancer. The matrix metalloproteinase-2 (MMP-2) responsive A/Au@MSMs-P promotes the separation of abemaciclib-loaded gold-silica nanoparticles (A/Au@MSMs) and anti-PD-1 antibody, achieving a triple-coordinated strategy to enhance checkpoint blockade therapy. First, chemo-photothermal therapy of A/Au@MSMs induces cell cycle arrest in G1 phase and promotes tumor cells apoptosis to achieve local ablation. Second, immunogenic death of tumor cells promotes the maturation of dendritic cells and recruits antigen-specific CTLs into tumor tissue to promote immune activation. Third, abemaciclib markedly suppresses the proliferation of regulatory T cells (Tregs) to alleviate the immunosuppression of the TME and potentiates the effectiveness of CTLs. This triple-coordinated strategy not only reshapes the antitumor immunity to enhance checkpoint blockade, but also cooperates with chemo-photothermal therapy, leading to improved antitumor efficiency and prolonged survival rate. Taken together, this study presents a promising strategy for improving checkpoint therapy response and has great potential in future cancer therapy.
研究领域:
肿瘤学
·
免疫疗法
·
纳米医学
·
癌症生物学
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2020
·
IF 7.242
Peipei Yang,Chao Lu,Wanbing Qin,Minglong Chen,Guilan Quan,Hu Liu,Lili Wang,Xuequn Bai,Xin Pan,Chuanbin Wu
Synergistic anti-tumor effect of anti-PD-1/L1 antibody (aPD-1/aPD-L1) and 1-methyl-D,L-tryptophan (1-MT) in melanoma has been well demonstrated, while efficient topical delivery systems are still largely unexplored. Here, a highly drug-concentrated hybrid core-shell microneedle (CSMN) system for co-delivery of checkpoint inhibitors was developed. Based on the specific drug-matrix interaction, the system concentrated aPD-L1 in the tips of microneedles through electrostatic interactions , and increased the amount of 1-MT loaded in CSMN by preventing its premature crystallization using PVA , the material used to prepare CSMN core. The prepared CSMN exhibited high transdermal delivery efficiency and long topical retention time of aPD-L1 for 2 days. Drug-loaded CSMN achieved better anti-tumor efficacy than the intra-tumor injection group at the same dose, which was likely because the former recruited more T lymphocytes to the tumor site. These findings suggested that this CSMN system was a promising local delivery system of both aPD-L1 and 1-MT for melanoma immunotherapy, and its unique core-shell structure could be readily adapted as a modular platform for various diseases, where combination therapy of both biomacromolecular drugs and other small-molecular agents were required. Statement of Significance In the present study, a core-shell microneedle (CSMN) system was constructed to achieve targeted co-delivery of checkpoint inhibitors to melanoma, while preventing significant systemic exposure. To overcome the drawback of insufficient drug loading of microneedles and effectively encapsulate two drugs simultaneously, microneedles were divided into two independent functional areas, a charged shell and a hydrophilic core and encapsulated drugs based on respective drug-matrix interaction. The charged shell prepared by chitosan could concentrate aPD-L1 in the tips of microneedles through electrostatic interactions. The core prepared by PVA successfully increased the amount of 1-MT loaded in microneedles by preventing its premature crystallization. The prepared CSMN exhibited high transdermal delivery efficiency and better anti-tumor efficacy than intra-tumor injection at the same dose.
研究领域:
药学科学
·
免疫学
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-17
·
IF 16.6
Fu Shunli,Chang Lili,Liu Shujun,Gao Tong,Sang Xiao,Zhang Zipeng,Mu Weiwei,Liu Xiaoqing,Liang Shuang,Yang Han,Yang Huizhen,Ma Qingping,Liu Yongjun,Zhang Na
Targeting tumour immunosuppressive microenvironment is a crucial strategy in immunotherapy. However, the critical role of the tumour lymph node (LN) immune microenvironment (TLIME) in the tumour immune homoeostasis is often ignored. Here, we present a nanoinducer, NIL-IM-Lip, that remodels the suppressed TLIME via simultaneously mobilizing T and NK cells. The temperature-sensitive NIL-IM-Lip is firstly delivered to tumours, then directed to the LNs following pH-sensitive shedding of NGR motif and MMP2-responsive release of IL-15. IR780 and 1-MT induces immunogenic cell death and suppress regulatory T cells simultaneously during photo-thermal stimulation. We demonstrate that combining NIL-IM-Lip with anti-PD-1 significantly enhances the effectiveness of T and NK cells, leading to greatly suppressed tumour growth in both hot and cold tumour models, with complete response in some instances. Our work thus highlights the critical role of TLIME in immunotherapy and provides proof of principle to combine LN targeting with immune checkpoint blockade in cancer immunotherapy.
研究领域:
癌症免疫疗法
·
纳米技术
·
免疫学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Yu-Xiang Ge,Tai-Wei Zhang,Lei Zhou,Wang Ding,Hai-Feng Liang,Zhi-Chao Hu,Qin Chen,Jian Dong,Feng-Feng Xue,Xiao-Fan Yin,Li-Bo Jiang
Poor immunogenicity and compromised T cell infiltration impede the application of immune-checkpoint blockade (ICB) immunotherapy for osteosarcoma (OS). Although autophagy is involved in enhancing the immune response, the synergistic role of autophagy in ICB immunotherapy and the accurate control of autophagy levels in OS remain elusive and challenging. Here, we designed a pH-sensitive autophagy-controlling nanocarrier, [email protected] @PEG-FA (CBZP), loading a natural derivative, curcumin (CUR), to boost the immunotherapeutic response of PD-1/PD-L1 blockade by activating immunogenic cell death (ICD) via autophagic cell death, and BMS1166 to inhibit the PD-1/PD-L1 interaction simultaneously, enhancing the tumor immunogenicity and sensitizing the antitumor T cell immunity. After entering tumor cells, the pH-sensitive nanoparticles induced autophagy and decreased the intracellular pH , which in turn further facilitated the release of CUR to enhance autophagic activity. Transferring CBZP to orthotopic OS tumor-bearing mice showed powerful antitumor effects and established long-term immunity against tumor recurrence, accompanied by enhanced dendritic cell maturation and tumor infiltration of CD8 + T lymphocytes. Collectively, CBZP exhibited synergistic effects in treating OS by combining ICD induction with checkpoint blockade, thereby shedding light on the use of autophagy control as a potential clinical therapy for OS.
研究领域:
肿瘤学
·
免疫疗法
·
纳米技术
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Xudong Fan,Tianxiang Yue,Aidi Liu,Xiaowei Xie,Weixiang Fang,Yinghui Wei,Hangsheng Zheng,Hongyue Zheng,Meiqi Zhou,Jigang Piao,Fanzhu Li
Photothermal therapy (PTT) has brought hope for cancer treatments, with hyperthermia-induced immunogenic cell death (ICD), which is a critical part of therapeutically induced antitumor immune responses. Limited immune stimulation response in PTT is the primary reason for incomplete tumor ablation, therefore demonstrating urgent requirements for ICD amplifier. Herein, a sub-10 nm supramolecular nanoassembly was formed by co-assembly of clinically approved aluminum adjuvant and commonly used indocyanine green (ICG) under the assistance of lignosulfonate (LS, a green and sustainable multifunctional lignin derivative) for localized photothermal-immunotherapy of breast cancer. The overall results revealed that LS-Al-ICG is capable of inducing amplified ICD, efficiently eliciting solid immune responses through dendritic cells (DCs) activation and cytotoxic T-cell responses initiation for tumor killing. Moreover, anti-PD-1 therapy blocked the PD-1 pathway and led to remarkable anti-tumor efficacy against laser-irradiated primary tumors and distant tumors by potentiating systemic tumor specific T cell immunity. The results of this study demonstrate a handy and extensible approach for engineering green natural lignin nanoparticles for cancer immunotherapy, which shows promise for delivering other therapeutics in biomedical applications.
研究领域:
癌症治疗
·
纳米技术
·
免疫疗法
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Reports Medicine
·
2025
·
IF 10.6
Liming Gui,Kaiwen Chen,Jingjing Yan,Ping Chen,Wei-Qiang Gao,Bin Ma
The induction of immunogenic cell death (ICD) impedes tumor progression via both tumor cell-intrinsic and -extrinsic mechanisms, representing a robust therapeutic strategy. However, ICD-targeted therapy remains to be explored and optimized. Through kinome-wide CRISPR-Cas9 screen, NUAK family SNF1-like kinase 1 (NUAK1) is identified as a potential target. The ICD-provoking effect of NUAK1 inhibition depends on the production of reactive oxygen species (ROS), consequent to the downregulation of nuclear factor erythroid 2-related factor 2 (NRF2)-mediated antioxidant gene expression. Moreover, the mevalonate pathway/cholesterol biosynthesis, activated by spliced form of X-box binding protein 1 (XBP1s) downstream of ICD-induced endoplasmic reticulum (ER) stress, functions as a negative feedback mechanism. Targeting the mevalonate pathway with CRISPR knockout or the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitor simvastatin amplifies NUAK1 inhibition-mediated ICD and antitumor activity, while cholesterol dampens ROS and ICD, and therefore also dampens tumor suppression. The combination of NUAK1 inhibitor and statin enhances the efficacy of anti-PD-1 therapy. Collectively, our study unveils the promise of blocking the mevalonate-cholesterol pathway in conjunction with ICD-targeted immunotherapy.
研究领域:
癌症研究
·
免疫学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Qiuqun Xiao,Jinyan Huang,Xing Wang,Zehong Chen,Weiqi Zhang,Fengjiao Liu,Jiejing Li,Zhimou Yang,Jie Zhan,Yanbin Cai
Tumor immunotherapy has become a research hotspot in cancer treatment, with macrophages playing a crucial role in tumor development. However, the tumor microenvironment restricts macrophage functionality, limiting their therapeutic potential. Therefore, modulating macrophage function and polarization is essential for enhancing tumor immunotherapy outcomes. Here, a supramolecular peptide amphiphile drug-delivery system (SPADS) is utilized to reprogram macrophages and reshape the tumor immune microenvironment (TIM) for immune-based therapies. The approach involved designing highly specific SPADS that selectively targets surface receptors of M2-type macrophages (M2-Mφ). These targeted peptides induced M2-Mφ repolarization into M1-type macrophages by dual inhibition of endoplasmic reticulum and oxidative stresses, resulting in improved macrophagic antitumor activity and immunoregulatory function. Additionally, TIM reshaping disrupted the immune evasion mechanisms employed by tumor cells, leading to increased infiltration, and activation of immune cells. Furthermore, the synergistic effect of macrophage reshaping and anti-PD-1 antibody (aPD-1) therapy significantly improved the immune system's ability to recognize and eliminate tumor cells, thereby enhancing tumor immunotherapy efficacy. SPADS utilization also induced lung metastasis suppression. Overall, this study demonstrates the potential of SPADS to drive macrophage reprogramming and reshape TIM, providing new insights, and directions for developing more effective immunotherapeutic approaches in cancer treatment.
研究领域:
癌症免疫治疗
·
纳米技术
·
药学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Shu Liang,Lingyun Xiao,Tian Chen,Paola Roa,Emiliano Cocco,Zhangwen Peng,Liu Yu,Meiying Wu,Jie Liu,Xizhe Zhao,Wenbin Deng,Xiongjun Wang,Chao Zhao,Yang Deng,Yang Mai
Intraperitoneal co-delivery of chemotherapeutic drugs (CDs) and immune checkpoint inhibitors (ICIs) brings hope to improve treatment outcomes in patients with peritoneal metastasis from ovarian cancer (OC). However, current intraperitoneal drug delivery systems face issues such as rapid drug clearance from lymphatic drainage, heterogeneous drug distribution, and uncontrolled release of therapeutic agents into the peritoneal cavity. Herein, we developed an injectable nanohydrogel by combining carboxymethyl chitosan (CMCS) with bioadhesive nanoparticles (BNPs) based on polylactic acid-hyperbranched polyglycerol. This system enables the codelivery of CD and ICI into the intraperitoneal space to extend drug retention. The nanohydrogel is formed by cross-linking of aldehyde groups on BNPs with amine groups on CMCS via reversible Schiff base bonds, with CD and ICI loaded separately into BNPs and CMCS network. BNP/CMCS nanohydrogel maintained the activity of the biomolecules and released drugs in a sustained manner over a 7 day period. The adhesive property, through the formation of Schiff bases with peritoneal tissues, confers BNPs with an extended residence time in the peritoneal cavity after being released from the nanohydrogel. In a mouse model, BNP/CMCS nanohydrogel loaded with paclitaxel (PTX) and anti-PD-1 antibodies (αPD-1) significantly suppressed peritoneal metastasis of OC compared to all other tested groups. In addition, no systemic toxicity of nanohydrogel-loaded PTX and αPD-1 was observed during the treatment, which supports potential translational applications of this delivery system.
研究领域:
药学
·
生物医学工程
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Meng He,Wei Xu,Yuxin Dan,Yue Pan,Yingying Li,Mingsheng Chen,Chang-Ming Dong
It is challenging for nanovaccines (NVs) to effectively deliver antigens/neoantigens to prime specifically potent immunities and remodel immunosuppressive tumor microenvironment (TME) for combating immune “cold” cancers. Herein, a novel kind of mannosylated fluoropolypeptide NVs of MFPCOFG (i.e., mannosylated fluoropoly( D,L -cysteine) ovalbumin-loaded Fe 2+ -gallic acid) is designed that synergistically integrates triple antigen-metal-thermoimmunity to remodel immunosuppressive TME and achieve highly potent immunities. MFPCOFG plus near-infrared irradiation (NIR) effectively facilitated antigen uptake and escape, induced the maturation and antigen cross-presentations of dendritic cells and macrophages, polarized anti-inflammatory macrophage phenotype M2 into tumoricial M1, primed potent CD4 + /CD8 + T cells responses, proinflammatory cytokines secretion and immune memory effects, showcasing triple antigen-metal-thermoimmunity outperforming combo/mono-immunity. Importantly, both MFPCOFG + NIR and personalized NVs can remarkably enhance the tumor infiltration of CD4 + /CD8 + T and NK cells to boost potent immunities and long-lasting memory effects, reduce regulatory T (Tregs) and M2 to remodel immunosuppressive TME in B16-OVA and 4T1 models, achieving superior tumor prevention, ablation, and tumor relapse and metastasis inhibition, as further orchestrated with anti-PD-1. Consequently, this work opens up a new avenue to design biocompatible polypeptide nanovaccines with potent immune-priming and TME-remodeling capabilities, holding great potentials to combat immune “cold” cancers with clinic-used anti-PD-1 for cancer immunotherapy and personalized immunotherapy.
研究领域:
癌症免疫治疗
·
纳米技术
·
免疫学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2020
·Vol. 6
·期 35
·
IF 13.117
Jingjing Liang,Huifang Wang,Wenxiu Ding,Jianxiang Huang,Xuefei Zhou,Huiyang Wang,Xue Dong,Guangyao Li,Enguo Chen,Fei Zhou,Hongjie Fan,Jingya Xia,Bo Shen,Da Cai,Pengxun Lan,Hanliang Jiang,Jun Ling,Zhen Cheng,Xiangrui Liu,Jihong Sun
Mounting evidence suggests that immunotherapies are a promising new class of anticancer therapies. However, the immunosuppressive tumor microenvironment (TME), poor immunogenicity, and off-target toxicity hinder the broader implementation of immunotherapies. Here, we describe a novel strategy combining chemotherapy and immunotherapy to modulate the TME by systemically and concurrently delivering the chemotherapeutic agent SN38 (7-ethyl-10-hydroxycamptothecin) and the STING agonist DMXAA (5,6-dimethylxanthenone-4-acetic acid) into tumors using triblock copolymer nanoparticles, named PS3D1@DMXAA, which enhances antigen cross-presentation and induces the conversion of the immunosuppressive TME to immunogenic TME through the newly found synergistic function between SN38 and STING activation. PS3D1@DMXAA thus shows potent therapeutic efficacy in three mice tumor models and elicits remarkable therapeutic benefit when combined with anti–PD-1 therapy. Our engineered nanosystem offers a rational design of an effective immunotherapy combination regimen to convert uninflamed “cold” tumors into “hot” tumors, addressing the major challenges immunotherapies faced.
研究领域:
肿瘤学
·
免疫疗法
·
纳米技术
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Yu Zhang,Qi Wang,Yishun Ji,Liyuan Fan,Binbin Ding,Jun Lin,Lili Wang
The challenge of photothermal therapy (PTT) clinical transformation is the limited penetration depth of laser light and the general concern of using synthetic photothermal nanomaterials. Hence, it is of great significance to develop combined cancer therapies based on NIR-II photothermal agents from natural materials. Herein, natural melanin nanoparticles from cuttlefish ink coated with large pore mesoporous SiO 2 were developed to load azodiisobutylimidazoline hydrochloride ( [email protected] ). After modification with (3-carboxypropyl) triphenylphosphonium bromide (CTPP), [email protected] nanoparticles showed enhanced retention in the tumor site and were further delivered to thermally susceptible mitochondria. Under 1064 nm laser irradiation, hyperthermia produced by melanin not only directly leads to cell death but also promotes AIPH release to generate oxygen-independent alkyl free radicals, which could further attack tumor cells. The collaboration of the photothermal effect of melanin and thermodynamic therapy of AIPH could induce a local antitumor immune response and effectively reprogram tumor-associated macrophages from the M2 to M1 phenotype. In combination with anti-PD-1 immune checkpoint blockade, the paralyzed immune system was awakened to inhibit and eliminate secondary metastatic tumors. The NIR-II-driven treatment in this paper can achieve energy conversion processes from NIR-II light to thermal energy and then to chemical energy to perform photothermal-dynamic therapy and immunotherapy. This will overcome the high side effects and insufficient antitumor immune response of PTT and provide a strategy for effective and mild antitumor therapy with clinically approved laser power and safe nanotechnology.
研究领域:
癌症治疗
·
纳米技术
·
光热治疗
·
免疫治疗
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·
IF 19
Xiangkai Zhang,Yangzi Yang,Jiaxin Li,Xinru Xie,Yongqiang Hao,Yingchun Zhu,Zhiyuan Zhang,Jingke Fu,Hailong Ma
Immunotherapy is a revolutionary achievement in cancer treatment. However, inadequate immune cells infiltration in tumor microenvironment (TME) always leads to treatment failure. Moreover, hypoxic TME hampers normal functions of immune cells. Here, it is found that hypoxia suppresses the STING signaling and immune cells activation in the work. Remodeling tumor immune microenvironment and relieving hypoxia are thus essential for enhancing immunotherapy efficiency. Herein, a spirulina platensis (SP)-based magnetic biohybrid system is constructed as an oxygen factory and loaded with stimulator of interferon genes (STING) agonist ADU-S100 (ADU@Fe-SP) for tumor immunotherapy. Magnet-guided biohybrid SP can actively target tumor tissues and produce oxygen in situ through photosynthesis, which reverses the hypoxic TME and facilitates the function of immune cells. Besides, the targeted delivery of ADU-S100 can activate the STING/TBK1/IRF3 signaling and boost cytokines production in tumor and innate immune cells. The ADU@Fe-SP system thus induces efficient immune cells infiltration in TME, which efficiently inhibits tumor progression and significantly enhances anti-PD-1 therapy efficiency in SCC VII-bearing tumor xenograft. ADU@Fe-SP exerts antitumor effect in a STING-dependent manner by in vivo STING-knockout mice model. The efficiency of this immunotherapy strategy is also demonstrated in patient-derived xenograft model originating from oral cancer, showing great clinical potential.
研究领域:
肿瘤学
·
免疫学
·
生物技术
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）