INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Shuangjun Li,Ruyue Shi,Yankun Liu,Mingcong Niu,Zhicun Liu,Zhongjuan Wang,Jiwang Gao,Hongda Cai,Zhuyu Zhou,Shengnan Li,Xiuhua Zhao
Immune cells infiltrating tumors play a pivotal role in tumor progression regulation; however, their functionality is frequently suppressed by the acidic conditions of the tumor microenvironment (TME). Targeting and reversing tumor acidity holds significant potential for enhancing the efficacy of immunotherapy. Here, we present a proof-of-concept study on tumor acidity-reversal therapy mediated by bacterial cellulose-targeted micelles to promote M2 macrophage repolarization to M1 macrophages and restore the anti-tumor function of T cells. Our strategy utilizes a bacterial cellulose (BC) composite modified with folic acid (FA) and chrysin (BY), loaded with lactic acid-neutralizing chemotherapeutic vincristine (VCR) and lactate dehydrogenase inhibitor GNE-140, to self-assemble into tumor-targeted nanoparticles. Post-treatment, FA-BC-BY@VCR@GNE-140 demonstrated notable efficacy in reversing tumor acidity, inducing tumor cell death, mitigating immunosuppression, and stimulating host adaptive immunity. This approach represents an innovative strategy for synergizing chemotherapy and immunotherapy to combat tumor progression.
研究领域:
肿瘤免疫学
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纳米医学
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药物递送
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肿瘤微环境
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免疫治疗
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生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
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2022
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IF 18.027
Lingxiao Zhang,Yingbo Jia,Jinju Yang,Lun Zhang,Shengjie Hou,Xiaoyun Niu,Jie Zhu,Yaru Huang,Xiaoying Sun,Zhi Ping Xu,Ruitian Liu
Cancer immunotherapy efficacy is largely limited by the suppressive tumor immune microenvironment (TIME) where antitumor immune cells are inhibited and tumor antigens continue to mutate or be lost. To remodel the TIME, we here applied weakly alkaline layered double hydroxide nanoparticles (LDH NPs) to neutralize the excess acid and block autophagy of tumor cells for neoadjuvant cancer immunotherapy. Peritumoral injection of LDH NPs provided a long-term and efficient acid-neutralization in the TIME, blocked the lysosome-mediated autophagy pathway in tumor cells, and increased the levels of antitumor tumor-associated macrophages and T cells. These LDH NPs captured tumor antigens released in the tumor tissues and effectively inhibited the growth of both melanoma and colon tumors in vivo. These findings indicate that LDH NPs, as an immunomodulator and adjuvant, successfully “awaken” and promote the host innate and adaptive immune systems, showing promising potential for solid tumor immunotherapy.
研究领域:
癌症研究
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纳米技术
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免疫学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2024
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IF 15.8
Liyun Zheng,Yiming Ding,Shiji Fang,Wenjing Yang,Jiale Chen,Ji Ma,Mengyuan Wang,Jiaoli Wang,Feng Zhang,Xiaoju Guo,Kun Zhang,Gao-Feng Shu,Qiaoyou Weng,Fazong Wu,Zhongwei Zhao,Minjiang Chen,Ji Jiansong
Unfavorable phenotypes characterized by low immunogenicity and acidity within the tumor microenvironment (TME) contribute to immunosuppression and therapeutic resistance. Herein, we rationally synthesized a multifunctional nanoregulator by encapsulating DOX and erianin into calcium carbonate (CaCO3)-based nanoparticles using a modified double emulsion method. The DOX and erianin-loaded CaCO3-based nanoparticles, termed DECaNPs, could effectively induce the calcium overload by triggering calcium influx and absorbing CaCO3 nanoparticles. Additionally, DECaNPs also neutralize the acidic TME by interacting with extracellular protons and limiting lactic acid production, a result of metabolic remodeling in cancer cells. As a result, DECaNPs elicit cellular oxidative stress damage, which mediates the activation of ferroptosis/apoptosis hybrid pathways, and profound immunogenic cell death. Treatment with DECaNPs could inhibit the growth of tumors by promoting oxidative stress, acid neutralization, metabolic remodeling, and protective antitumor immunity in vivo. In addition, DECaNPs could synergistically amplify the antitumor effects of αPD-L1 in a bilateral tumor model by eliciting systemic immune responses. In all, our work presents the preparation of CaCO3-based nanoregulators designed to reverse the unfavorable TME and enhance αPD-L1 immunotherapy through multiple mechanisms.
研究领域:
肿瘤学
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药学
·
纳米技术
·
免疫学
·
癌症治疗
✓ 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）