Nano Today
·
2025
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IF 10.9
Yating Qin,Yan Lin,Chao Tian,Yujie Qi,Shuling Wang,Xiaoyuan Chen,Wenxing Gu
Immune checkpoint blockade (ICB) therapy has emerged as a promising avenue for the treatment of malignant tumors. Nonetheless, the efficacy of this approach is constrained by low anti-tumor immunity and restricted intratumoral delivery of immune checkpoint inhibitors (ICIs) in solid tumors. In this study, a pH-responsive nanocomplex (BRM/PTX/aPD-1) was developed for the active transport of aPD-1 and PTX, thereby enhancing cancer chemoimmunotherapy. BRM/PTX/aPD-1 was prepared by using dynamic and reversible benzoic-imine bonds cross-linked bovine albumin (BSA), anti-PD-1 antibody (aPD-1) and PTX-loaded polylysine dendrimers. In the acidic tumor microenvironment, BRM/PTX/aPD-1 exhibited a charge reversal from negative to positive due to the hydrolysis of the β-carboxylic amide structure, which triggered cation-induced transcytosis. This process enabled active transport of adequate amounts of BRM/PTX/aPD-1 to the tumor parenchyma, where it was degraded by further hydrolysis of benzoic-imine bonds and effectively released aPD-1 and PTX. The nanocomplex demonstrated notable intratumoral permeability both in vitro and in vivo , particularly enhancing the delivery of aPD-1. Additionally, the nanocomplex showed robust anti-tumor activity in an orthotopic breast cancer model, significantly inhibiting tumor proliferation and preventing the progression of lung metastasis. This pH-responsive nanocomplex presents a promising platform for improved intratumoral delivery of ICIs and emerges as a practical solution for overcoming tumor immunosuppression.
研究领域:
肿瘤学
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药剂学
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免疫学
✓ 已验证
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
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IF 4.8
Ningchao Luo,Lisha Ma,Ninghui Ma,Jiale Wei,Hongyan Zhang,Wanyu Jin,Yujie Li,Jingbin Shi,Yang Xiong
Triple negative breast cancer (TNBC) represents a heterogeneous subtype of breast cancer characterized by an unfavorable prognosis due to its aggressive biology. Cancer-associated adipocytes (CAAs) play an active role in tumor development, invasion and metastasis, and response to treatment by secreting various cytokines. CAAs secrete CCL2 and ADPN which significantly affect the efficacy of aPD-1 in treating breast cancer. Our recent research has demonstrated that Hesperidin, a natural phenolic compound, significantly inhibits CCL2, elevates ADPN secreted by CAAs in vitro and in vivo, remodels the immune microenvironment, and potentiates the efficacy of aPD-1 in triple-negative breast cancer. We used Oil red staining, Bodipy 493/503 staining and quantitative real-time PCR to verify the formation of CAAs. ELISA was used to detect levels of CCL2, ADPN secreted by CAAs. Changes in the number of immune cells in mouse tumor tissues were detected using flow cytometry and immunofluorescence. Our data suggest that Hesperidin PLGA nanoparticles significantly reduced CCL2 and increased ADPN secreted by CAAs, which concurrently decreased the recruitment of M2 macrophages, Tregs and MDSCs while increased the infiltration of CD8 + T cells, M1 macrophages and DCs into tumor, thus significantly potentiated the efficacy of aPD-1 in vivo. This study provides a new combined strategy for the clinical treatment of triple-negative breast cancer by interfering with CCL2, ADPN secreted by CAAs to enhance the efficacy of immunotherapy.
研究领域:
肿瘤学
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免疫学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF POLYMER SCIENCE
·
2022
·Vol. 60
·期 10
·1595-1609
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IF 3.046
Junfeng Ding,Tianran Wang,Zhixiong Chen,Zhiqiang Lin,Xuesi Chen,Chaoliang He
The efficiency of antitumor immunotherapy is usually limited by the immunosuppressive tumor microenvironment (TME). In this study, we developed a chemo-immunotherapy strategy that is able to improve the immunosuppressive TME for enhancing the antitumor efficacy. The chemo-immunotherapy was achieved by the topical co-delivery of a chemotherapeutic drug, Doxorubicin (DOX), an immune checkpoint blocking antibody targeting programmed cell death protein 1 (aPD-1), and an indoleamine-2,3-dioxygenase (IDO) inhibitor, 1-methyl- d -tryptophan ( d -1MT) by using a thermosensitive polypeptide hydrogel. It was revealed that the sustained DOX release from the hydrogel caused the immunogenic cell death (ICD) of B16F10 cells in vitro, and the tumor cell lysates subsequently promoted the activation of dendritic cells (DCs). After intratumoral injection into B16F10 melanoma-bearing mice, the DOX/aPD-1/D-1MT co-loaded hydrogel exhibited enhanced tumor inhibition efficacy and prolonged animal survival time, compared to the DOX/aPD-1/D-1MT mixed solution, DOX-loaded hydrogel or DOX/aPD-1 co-loaded hydrogel. The improvement of immunosuppressive TME and enhancement of antitumor immune response after the local chemo-immunotherapy were demonstrated by the augmented activation of DCs and increased infiltration of CD8 + and CD4 + T cells, as well as enhanced secretion of pro-inflammatory cytokines. Therefore, the hydrogel-based local chemo-immunotherapy system holds great potential for effective antitumor treatment. Graphical
研究领域:
肿瘤学
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生物材料
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免疫学
✓ 已验证
DOI
高影响因子
MATERIALS & DESIGN
·
2023
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IF 8.4
Wenqi Jiang,Mingkang Liang,Qifang Lei,Dashi Deng,Chenchen Li,Yuqing Li,Simin Yuan,Kai Wu,Guangzhi Li,Song Wu
Mucosa administration and transmucosal polymeric carriers demonstrate specific advantages in locoregional therapy, which, however, suffer from unsatisfactory transmucosal delivery efficiency and limited hydrophobic or bio-macromolecular drug loading. Herein, we demonstrate several phenylboronic acid-modified chitosan derivatives to screen out a self-assembly nano-system. The phenylboronic acid unit synthesized in chitosan skeleton (CS) afforded donor–acceptor coordination with amidogen of pirarubicin (THP) and aPD-1 [1] , [2] , [3] ,the drug loading content was increased from 18.2 ± 0.4% to 37.0 ± 1.0% compared with CS. Besides, the phenylboronic acid modification provided an additional transmucosal advantage for cationic CS via non-covalent binding with mucosal glycosaminoglycans and enhanced the penetration ability of drugs through the endocytosis, Golgi-endoplasmic reticulum and exocytosis pathway. Furthermore, the encapsulated agents can be selectively released in response to the high reactive oxygen species concentration in tumor tissues, which combined with enhanced transmucosal capacity extremely contribute to improving the therapeutic efficacy and biosafety of [email protected] and [email protected] NPs in bladder cancer perfusion therapy as well as lung cancer inhalation treatment. Even more exciting is that in addition to THP and aPD-1, our platform could be easily extended to other chemotherapeutics and bio-macromolecular agents with electron-donating groups, rendering a simple and robust strategy for enabling highly efficient mucosal administration-based cancer therapy.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Nano
·
2022
·
IF 13.364
Guanping He,Yajun Shuai,Yong Hai,Tao Yang,Xiaoyu Pan,Yuzeng Liu,Xianglong Meng,Honghao Yang,Mingying Yang,Chuanbin Mao
One of the challenges in immunotherapy is the difficulty for immune checkpoint blockers to seek and destruct ‘cold’ tumors. Here we tackled this challenge using a new nanomaterial with the capability of tumor targeting, photoablation, and immune checkpoint blocking, leading to successful eradication of primary and distant metastatic tumors by photothermal immunotherapy. Specifically, the programmed death receptor 1 antibody (aPD-1) was grafted onto novel Au nanodendrites (AuNDs) to prepare a complex ( [email protected] ). The dendritic structure of [email protected] enabled sustained release of aPD-1 for blocking immune checkpoints and effective photoablation upon near-infrared irradiation for making tumors ‘hot’. Using osteosarcoma (OS) as a model ‘cold’ tumor, we found that intravenous injection of [email protected] , followed by near-infrared irradiation only on the primary tumor, destroyed primary and distant metastatic OS via activating T cells and blocking PD-1/programmed death-ligand 1 axis. The photothermal immunotherapy led to tumor eradication with a prolonged survival of mice and exhibited long-term immune memory to prevent tumor reinvasion and recurrence. [email protected] presented good tumor-targeting ability due to a combination of nanomaterials-based passive targeting and antibody-enabled active targeting and thus was excreted in the blood circulation through a special hepatointestinal pathway. Hence, the [email protected] is a promising biomaterial for treating metastatic OS through photothermal immunotherapy.
研究领域:
肿瘤学
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纳米技术
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免疫疗法
✓ 已验证
产品关联
DOI
高影响因子
Small
·
2023
·
IF 13.3
Xiaodan Wei,Honglin Huang,Junhan Guo,Ningxi Li,Qingzhi Li,Tian Zhao,Geng Yang,Lulu Cai,Hong Yang,Chunhui Wu,Yiyao Liu
Reprogramming the immunologically “cold” environment of solid tumors is currently becoming the mainstream strategy to elicit powerful and systemic anticancer immunity. Here, a facile and biomimetic nano-immunnoactivator ( CuS/Z@M 4T1 ) is detailed by engineering a Zn 2+ -bonded zeolitic imidazolate framework-8 (ZIF-8) with CuS nanodots (NDs) and cancer cell membrane for amplified near-infrared-II (NIR-II) photothermal immunotherapy via Zn 2+ metabolic modulation. Taking advantage of the NIR-II photothermal effect of CuS NDs and the acidic responsiveness of ZIF-8, CuS/Z@M 4T1 rapidly causes intracellular Zn 2+ pool overload and disturbs the metabolic flux of 4T1 cells, which effectively hamper the production of heat shock proteins and relieve the resistance of photothermal therapy (PTT). Thus, amplified immunogenic cell death is evoked and initiates the immune cascade both in vivo and in vitro as demonstrated by dendritic cells maturation and T-cell infiltration. Further combination with antiprogrammed death 1 (aPD-1) achieves escalated antitumor efficacy which eliminates the primary, distant tumor and avidly inhibits lung metastasis due to cooperation of enhanced photothermal stimulation and empowerment of cytotoxic T lymphocytes by aPD-1. Collectively, this work provides the first report of using the intrinsic modulation property of meta-organometallic ZIF-8 for enhanced cancer photoimmunotherapy together with aPD-1, thereby inspiring a novel combined paradigm of ion-rich nanomaterials for cancer treatment.
研究领域:
纳米技术
·
癌症免疫治疗
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生物医学工程
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材料科学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMISTRY
·
2024
·
IF 5.5
Junfeng Ding,Tianran Wang,Yan Rong,Chaoliang He,Xuesi Chen
Comprehensive Summary Due to the immunosuppressive tumor microenvironment (TME), T cells are usually inactivated and tend to differentiate into regulatory T cells (Tregs) in the tumor tissues, which seriously hinders the anti-tumor efficiency of immunotherapy. In this study, an immune-stimulating polypeptide hydrogel conjugated with an indoleamine-2,3-dioxygenase (IDO) inhibitor, 1-methyl- D -tryptophan (D1MT), through a glutathione (GSH)-responsive spacer was developed as an immunotherapy platform capable of regulating the TME. A combined immunotherapy system was further constructed through encapsulating doxorubicin (Dox) and immune checkpoint blocking antibody targeting programmed cell death protein 1 (aPD-1) in the hydrogel. Dox released from the hydrogel could cause the immunogenic cell death (ICD) of tumor cells and induce the maturation of antigen presenting cells (APCs). After intratumoral injection, the multiple agent-loaded hydrogel elicited effective anti-tumor immunity in mice bearing B16F10 melanoma. Moreover, compared with the control hydrogel without D1MT, the immune-stimulating hydrogel showed better efficiency in improving the immunosuppressive TME with increased number of activated T cells and reduced number of Tregs. Therefore, the immune-stimulating hydrogel has great potential as a stimuli-responsive platform for regulating suppressive TME and enhanced anti-tumor chemo-immunotherapy.
研究领域:
癌症免疫疗法
·
药学
·
生物医学工程
·
免疫学
·
肿瘤学
✓ 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）