Biomaterials Advances
·
2025
·
IF 6
Xingjian Yan,Han Dong,Liyin Gao,Mengqi Liu,Chunxi Wang
Prostate cancer (PCa) is commonly considered a “cold tumor” due to its immunosuppressive microenvironment. Cold tumors are typically identified by the absence of T-cell infiltration within the tumor, while other immune populations and myeloid cells can be observed in these tumors. To achieve light-heat combined immunotherapy checkpoint inhibitor treatment for castration-resistant prostate cancer, we aimed to transforming “cold tumors” into “hot tumors”. We designed and synthesized a two-dimensional material, selenium-doped black phosphorus (BP), to enhance the photothermal conversion efficiency, and formed Se@BPNSs by liquid-phase exfoliation. To address the issue of enhanced permeability and retention effect, and to achieve efficient targeting, we coated the Se@BPNSs with RM-1 cell membrane derived from mouse prostate cancer cells. By injecting a certain dose of Se@BPNSs into the tumor and irradiating with a 808 nm laser, the Se@BPNSs converted light energy into heat to kill tumor cells at high temperatures while releasing antigens captured by dendritic cells. In addition, we combined the immunotherapy checkpoint inhibitor anti-PD1 to enhance the immune response and promote immune cell infiltration. The successful preparation of Se@BPNSs was verified through material characterization, cell-level and animal-level experiments, and the antitumor effect was meanwhile verified, which further provided guidance for prostate cancer treatment by photothermal synergistic immunotherapy.
研究领域:
生物医学工程
·
肿瘤免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Feiran Zhang,Jingwen Dong,Kan Huang,Bowen Duan,Chenzi Li,Ruoxi Yang,Jing Li,Feng Zhi,Zhanwei Zhou,Minjie Sun
Pathophysiological barriers in “cold” tumors seriously limit the clinical outcomes of chemoimmunotherapy. These barriers distribute in a spatial order in tumors, including immunosuppressive microenvironment, overexpressed chemokine receptors, and dense tumor mesenchyme, which require a sequential elimination in therapeutics. Herein, we reported a “dominolike” barriers elimination strategy by an intratumoral ATP supersensitive nanogel (denoted as BBLZ-945@PAC–PTX) for enhanced chemoimmunotherapy. Once it has reached the tumor site, BBLZ-945@PAC–PTX nanogel undergoes supersensitive collapse triggered by adenosine triphosphate (ATP) in perivascular regions and releases BLZ-945 conjugated albumin (BBLZ-945) to deplete tumor-associated macrophages (TAMs). Deeper spatial penetration of shrunk nanogel (PAC–PTX) could not only block CXCR4 on the cell membrane to decrease immunosuppressive cell recruitment but also internalize into tumor cells for tumor-killing and T cell priming. The strategy of “dominolike” barriers elimination in tumors enables immune cell infiltration for a potentiated immune response and offers a high-responsive treatment opinion for chemoimmunotherapy.
研究领域:
肿瘤学
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药剂学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2024
·Vol. 15
·期 12
·1-14
·
IF 8.1
Zheng Zhen-Yuan,Lin Wan,Su Jia-Wan,Huang Qing-Feng,Zhang Cong,Pan Wen-Xing,Li En-Min,Zhang He-Feng,Xu Li-Yan
Effectively interfering with endoplasmic reticulum (ER) function in tumor cells and simultaneously activating an anti-tumor immune microenvironment to attack the tumor cells are promising strategies for cancer treatment. However, precise ER-stress induction is still a huge challenge. In this study, we synthesized a near-infrared (NIR) probe, NIR-715, which induces tumor cell death and inhibits tumor growth without causing apparent side effects. NIR-715 triggers severe ER stress and immunogenic cell death (ICD) after visible light exposure. NIR-715 induced ICD-associated HMGB1 release in vitro and anti-tumor immune responses, including increased cytotoxic T lymphocyte (GZMB + CD8 + T cell) infiltration and decreased numbers of exhausted T lymphocytes (PD-L1 + CD8 + T cell). These findings suggest that NIR-715 may be a novel agent for “cold” tumor photodynamic therapy (PDT). Schematic illustration of NIR-715 photodynamic therapy for visible light-triggered, endoplasmic reticulum-targeting antitumor therapy.
研究领域:
肿瘤学
·
免疫疗法
·
光动力疗法
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Kun Tu,Huan Deng,Li Kong,Yi Wang,Ting Yang,Qian Hu,Mei Hu,Conglian Yang,Zhiping Zhang
Blocking immune checkpoints with monoclonal antibody has been verified to achieve potential clinical successes for cancer immunotherapy. However, its application has been impeded by the “cold” tumor microenvironment. Here, weak acidity-responsive nanoparticles co-loaded with CRISPR/Cas9 and paclitaxel (PTX) with the ability to convert “cold” tumor into “hot” tumor are reported. The nanoparticles exhibited high cargo packaging capacity, superior transfection efficiency, well biocompatibility, and effective tumor accumulation. The CRISPR/Cas9 encapsulated in nanoparticles could specifically knock out cyclin-dependent kinase 5 gene to significantly attenuate the expression of programmed death-ligand 1 on tumor cells. More importantly, PTX co-delivered in nanoparticles could significantly induce immunogenic cell death, reduce regulatory T lymphocytes, repolarize tumor-associated macrophages, and enhance antitumor immunity. Therefore, the nanoparticles could effectively convert cold tumor into hot tumor, achieve effective tumor growth inhibition, and prolong overall survival from 16 to 36 days. This research provided a referable strategy for the development of combinatorial immunotherapy and chemotherapy.
研究领域:
癌症免疫治疗
·
纳米技术
·
基因编辑
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2020
·Vol. 7
·期 17
·2000411
·
IF 15.84
Qinjun Chen,Yongqing He,Yu Wang,Chao Li,Yujie Zhang,Qin Guo,Yiwen Zhang,Yongchao Chu,Peixin Liu,Hongyi Chen,Zheng Zhou,Wenxi Zhou,Zhenhao Zhao,Xiaomin Li,Tao Sun,Chen Jiang
Lack of tumor-infiltration lymphocytes (TILs) and resistances by overexpressed immunosuppressive cells (principally, myeloid-derived suppressor cells (MDSCs)) in tumor milieu are two major challenges hindering the effectiveness of immunotherapy for “immune-cold” tumors. In addition, the natural physical barrier existing in solid cancer also limits deeper delivery of drugs. Here, a tumor-targeting and light-responsive-penetrable nanoplatform (Apt/PDGs ^ s@pMOF) is developed to elicit intratumoral infiltration of cytotoxic T cells (CTLs) and reeducate immunosuppressive microenvironment simultaneously. In particular, porphyrinic metal–organic framework (pMOF)–based photodynamic therapy (PDT) induces tumor immunogenic cell death (ICD) to promote CTLs intratumoral infiltration and hot “immune-cold” tumor. Upon being triggered by PDT, the nearly 10 nm adsorbed drug-loaded dendrimer de-shields from the nanoplatform and spreads into the deeper tumor, eliminating MDSCs and reversing immunosuppression, eventually reinforcing immune response. Meanwhile, the designed nanoplatform also has a systemic MDSC inhibition effect and moderate improvement of overall antitumor immune responses, resulting in effective suppression of distal tumors within less significant immune-related adverse effects (irAEs) induced.
研究领域:
癌症生物学
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免疫学
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Shengsheng Mei,Shanshan Peng,Eu Gene Vong,Jinbiao Zhan
Background Clinical data indicate that a substantial portion of cancer patients, though eligible for immune checkpoint inhibitor (ICI) therapy, cannot fully benefit from ICI monotherapy due to the poor immunogenicity of tumors and lack of tumor-infiltrating lymphocytes within the ‘cold’ tumor microenvironment (TME). In addition to poor antibody penetrance into the TME, systemic delivery of ICIs is associated with immune-related adverse events (irAEs) among recipients, some of which are life-threatening. Oncolytic virotherapy is a potentially viable approach to improving the efficacy of ICI therapy because of their ability to selectively replicate and lyse tumor cells, release tumor-associated antigens (TAAs), induce inflammatory response and promote lymphocyte infiltration in tumors. Methods A recombinant oncolytic adenoviruses (OAd), denoted ZD55-aPD-L1 scFv, which carried the expression cassette for anti-PD-L1 scFv was constructed by molecular cloning. Western blot and ELISA assay were performed to detect aPD-L1 scFv expression. Flow cytometry were used to analyse PD-L1 expression and count tumor cells. Co-culture assay of human peripheral blood mononuclear cells (PBMCs) with tumor cells in vitro and triple-negative breast cancer (TNBC) MDA-MB-231 tumor-bearing model in vivo were evaluated the antitumor effects of recombinant oncolytic adenoviruses ZD55-aPD-L1 scFv. Results We found that cells infected with recombinant oncolytic adenovirus ZD55-aPD-L1 scFv can effectively express aPD-L1 scFv, which function similarly to its full-length anti-PD-L1 antibody. PBMCs have inherently very limited killing effect on tumor cells even with administration of anti-PD-L1 antibody as observed from our in vitro co-cultures. Treatment consisting of ZD55 alone or ZD55 combined with anti-PD-L1 antibody yielded mediocre antitumor efficacy in subsequent in vitro and in vivo investigations, but were all substantially surpassed by the synergistic antitumor effects observed with ZD55-aPD-L1 scFv treatment. We show that the concomitant direct oncolysis by the recombinant OAd and localized autocrine/paracrine interception of PD-1:PD-L1 checkpoint interaction mediated by ZD55-aPD-L1 scFv-infected cells is exceedingly superior to co-administration of ZD55 and anti-PD-L1 antibody in the human TNBC mice model. Conclusions Our results provided evidence for the development of novel strategies, in this case an anti-PD-L1 scFv-armed OAd, to bolster immune responses to ‘cold’ tumors and to improve therapeutic responsiveness to ICIs.
研究领域:
肿瘤学
·
免疫疗法
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Matter
·
2022
·
IF 19.967
Yunfei Yi,Mian Yu,Chan Feng,Huisong Hao,Weiwei Zeng,Chuchu Lin,Hongzhong Chen,Feng Lv,Dunwan Zhu,Xiaoyuan Ji,Lin Mei,Meiying Wu,Wei Tao
Summary It is highly desirable to turn “cold” tumors into “hot” ones to improve the efficacy of antitumor immunotherapy. Herein, we develop the peptide-based small interfering RNA (siRNA) micelleplexes (P A7R @siPD-L1) for normalizing vascular-immune crosstalk to establish a positive feedback loop in potentiating antitumor immunotherapy. These micelleplexes are equipped with tumor-microenvironment-responsive property for precise drug delivery and release. The prepared P A7R @siPD-L1-mediated photodynamic therapy could eliminate solid tumors and trigger immunogenic cell death to generate systematic immune responses. Meanwhile, the antiangiogenic peptide A7R normalizes the tumor vasculature by converting chaotic vascular systems into matured and organized ones, thus alleviating tumor hypoxia and promoting intratumoral infiltration by immune cells. Antitumor immunogenicity would be further strengthened with the aid of siPD-L1 by muting the resistance of tumor cells against immune effector cells. This study provides a unique therapeutic strategy in turning “cold” tumors into “hot” tumors enabled by siRNA nanomaterial .
研究领域:
肿瘤学
·
免疫疗法
·
纳米医学
·
癌症生物学
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Qingle Song,Guofang Zhang,Bo Wang,Guoli Cao,Dongjie Li,Yu Wang,Yuqian Zhang,Jin Geng,Hongchang Li,Yang Li
Although immuno-oncotherapy in clinic has gained great success, the immunosuppressive tumor microenvironment (TME) existing in the “cold” tumor with insufficient and exhausted lymphocytes may result in a lower-than-expected therapeutic efficiency. Therefore, a properly designed synergistic strategy that can effectively turn the “cold” tumor to “hot” should be considered to improve the therapeutic effects of immuno-oncotherapy. Herein, TME-responsive penetrating nanogels (NGs) were developed, which can improve the delivery and penetration of the co-loaded resiquimod (R848) and green tea catechin (EGCG) in tumors by a nano-sized controlled releasing system of the soluble cyclodextrin-drug inclusion complex. Consequently, the NGs effectively promoted the maturation of dendritic cells, stimulated the cytotoxic T lymphocytes (CTLs), and decreased the PD-L1 expression in tumors. The combination of NGs with the OX40 agonist (αOX40) further synergistically enhanced the activation and infiltration of CTLs into the deep tumor and inhibited the suppression effects from the regulatory T cells (Tregs). As a result, an increased ratio of active CTLs to Tregs in tumors (20.66-fold) was achieved with a 91.56% tumor suppression effect, indicating a successful switch of “cold” tumors to “hot” for an immunologically beneficial TME with significantly improved anti-tumor immune therapeutics. This strategy could be tailored to other immuno-oncotherapeutic approaches to solve the urgent efficiency concerns of the checkpoint-based treatment in clinic.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
Tian Zhang,Dongsheng Tang,Pengfei Wu,Shaoping Jiang,Yuquan Zhang,Abid Naeem,Yong Li,Chunhui Li,Bo Hu,Shuai Guo,Caixia Sun,Haihua Xiao,Ran Yan,Yuhua Weng,Yuanyu Huang
Immune checkpoint blockade (ICB) therapy is a widely favored anti-tumor treatment, but it shows limited response to non-immunogenic “cold” tumors and suffers from drug resistance. Photodynamic therapy (PDT), as a powerful localized treatment approach, can convert a “cold tumor” into a “hot tumor” by inducing immunogenic cell death (ICD) in tumor cells, thereby enhancing tumor immunogenicity and promoting tumor immunotherapy. However, the effectiveness of PDT is largely hindered by the limited penetration depth into tumor tissues. To address these issues, we proposed an all-in-one drug system with NIR-II photo-accelerated PDT effects, efficient immune checkpoint gene silencing, and a facile manufacturing process. The so-called all-in-one drug system comprises a multi-modal designed polymer PPNP and siRNA. PPNP is an amphipathic polymer that includes the near infrared-II (NIR-II) photosensitizer Aza-boron-dipyrromethene (Aza-BODIPY), a glutathione (GSH)-cleavable linker, and a cationic monomer derived from cholesterol. PPNP can self-assemble and efficiently load siRNA. Under laser irradiation, PPNP triggers a potent ICD cascade, causing the on-demand release of siPD-L1, reshaping the tumor's immunosuppressive microenvironment, effectively inhibiting the growth of various tumors, and stimulating the immune memory. This study represents a generalized platform for PDT and gene silencing, designed to modulate immune-related signaling pathways for improved anticancer therapy.
研究领域:
肿瘤学
·
免疫治疗
·
药理学
·
生物医学工程
·
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）