Bioactive Materials
·
2023
·
IF 18.9
Zhenhao Zhao,Chufeng Li,Yiwen Zhang,Chao Li,Yongchao Chu,Xuwen Li,Peixin Liu,Hongyi Chen,Yu Wang,Boyu Su,Qinjun Chen,Tao Sun,Chen Jiang
A long-standing paucity of effective therapies results in the poor outcomes of triple-negative breast cancer brain metastases. Immunotherapy has made progress in the treatment of tumors, but limited by the non-immunogenicity of tumors and strong immunosuppressive environment, patients with TNBC brain metastases have not yet benefited from immunotherapy. Dual immunoregulatory strategies with enhanced immune activation and reversal of the immunosuppressive microenvironment provide new therapeutic options for patients. Here, we propose a cocktail-like therapeutic strategy of microenvironment regulation-chemotherapy-immune synergistic sensitization and construct reduction-sensitive immune microenvironment regulation nanomaterials ( [email protected] ). [email protected] modified with targeting peptide penetrates the BBB and is subsequently internalized into metastatic breast cancer cells, releasing silybin and oxaliplatin responsively in the cells. [email protected] preferentially accumulates at the metastatic site and can significantly prolong the survival period of model animals. Mechanistic studies have shown that [email protected] can effectively induce immunogenic cell death of metastatic cells, activate immune responses and increase infiltration of CD8 + T cells. Meanwhile, the activation of STAT3 in the metastatic foci is attenuated and the immunosuppressive microenvironment is reversed. This study demonstrates that [email protected] with dual immunomodulatory functions provides a promising immune synergistic therapy strategy for breast cancer brain metastases.
研究领域:
肿瘤学
·
免疫学
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Yan Chen,Ming Zhang,Yanqin He,Suying Li,Shuaiqi Feng,Zhifang Liu,Ning Zhang,Meifeng Liu,Qingpeng Wang
Epithelial–mesenchymal transition (EMT) is a critical process for cancer progression, which is crucial in inhibiting the immunity in tumors and further boosting tumor metastasis. The suppression of EMT represents a promising strategy for inhibiting metastatic tumors. Herein, a series of new canadine platinum(IV) conjugates with potent antiproliferative and antimetastatic activities were developed, which activated by suppressing EMT and provoking immune response in tumors besides causing DNA injury. The complexes could covalently conjugate to DNA and induce mitochondria-mediated apoptosis via Bcl-2/Bax/caspase3 signaling. The EMT process was remarkably inhibited by suppressing the Wnt/β-catenin pathway, reversing the inflammatory tumor microenvironment, and inhibiting the HIF-1α pathway, which further resulted in the inhibited angiogenesis in tumors. Moreover, the antitumor immunity was elevated by blocking immune checkpoints PD-L1 and CD47 accompanied by the improvement of CD3+ and CD8+ T lymphocytes and the macrophage polarization from M2- toward M1-type simultaneously in tumors.
研究领域:
癌症生物学
·
药理学
·
免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Cong Cong,Xuejiao Gao,Fei Ye,Xuwu Zhang,Yuchu He,Zhenhe Ma,Wenkang Tu,Weili Xue,Kelong Fan,Dawei Gao
In cancer, the infiltration of immune cells is significantly impeded by aberrantly elevated tumor interstitial fluid pressure (TIFP, a typical mechanical force). For reducing TIFP to augment immunoinfiltration, we synthesized a Fe-doped crystalline carbon nitride as nano-actuators (CFL@M), which can effectively reduce TIFP by piezo/photo-catalytically interstitial fluid splitting. As the mechanical forces change in tumors (TIFP decreased to 60.79%), the trafficking of immune cells into deep tumor tissue were notably facilitated. Among them, the infiltration of dendritic cells was enhanced by 13.02%, and that of M1-type macrophages was enhanced by 30.34%. Moreover, CD4 + T cells and CD8 + T cells responded to changes of fluid pressure by aggregating towards the tumor center. Therefore, the nano-actuators provide a promising mechanosensitive immunotherapy by reducing interstitial fluid pressure to sustain an effective infiltration of immune cells, which results in significant therapeutic benefits such as retarded tumor growth (72.6%), inhibited tumor metastasis (76.56%) and extended survivals. Briefly, this nano-actuator with good biosafety is a new endeavor in the field of “mechano-immunology”.
研究领域:
纳米技术
·
免疫治疗
·
癌症生物学
·
力学生物学
·
生物工程
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Mei Long,Yanfeng Zhou,Daoxia Guo,Qingyun Zhu,Huan Liang,Xiaoyuan Ji,Nan Chen,Haiyun Song
Epigenetic drugs (epi-drugs) can destruct cancer cells and initiate both innate and adaptive immunity, yet they have achieved very limited success in solid tumors so far, partly attributing to their concurrent induction of the myeloid-derived suppressor cell (MDSC) population. Here, dissociable Siamese nanoparticles (SIANPs) are developed for tumor cell-targeted delivery of epi-drug CM-272 and MDSC-targeted delivery of small molecule inhibitor Ibrutinib. The SIANPs are assembled via interparticle DNA annealing and detached via tumor microenvironment-triggered strand separation. Such binary regulation induces endogenous retrovirus expression and immunogenic cell death in tumor cells while restraining the immunosuppressive effects of MDSCs, and synergistically promotes dendritic cell maturation and CD8 + T cell activation for tumor inhibition. Significantly, immune microenvironment remodeling via SIANPs further overcomes tumor resistance to immune checkpoint blockade therapy. This study represents a two-pronged approach for orchestrating immune responses, and paves a new way for employing epi-drugs in cancer immunotherapy.
研究领域:
癌症免疫疗法
·
纳米技术
·
药理学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Xia Dong,Jie Liang,Afeng Yang,Zhiyong Qian,Deling Kong,Feng Lv
As synergistic photothermal immunotherapy has developed as one of the most attractive strategies for cancer therapy, it is crucial to design an effective photothermal immunotherapy system to enhance the synergistic anti-tumor effect and reveal the essential role of each treatment. In this study, we designed CpG self-crosslinked nanoparticles-loaded IR820-conjugated hydrogel with dual self-fluorescence to exert the combined photothermal-immunotherapy. IR820-hydrogel can be effective for hyperthermia to eliminate the primary tumor based on its comprehensive coverage and generated photothermal-induced tumor antigens for assisted immunotherapy. CpG self-crosslinked nanoparticles improved the immune response of adjuvant against melanoma without extra nano-carriers. The synergistic photothermal immunotherapy was achieved by the merging of CpG self-crosslinked nanoparticles and IR820-hydrogel. A possible mechanism of combined antitumor effect was further revealed by analyzing immune cells including CD8 + T cells , DCs, B cells, Treg and MDSC in tumor microenvironment . The specific antitumor immunity was provoked to remove the tumor residues and ultimately the combined treatment mode achieved more effective systemic therapeutic effect than either photothermal therapy or immunotherapy alone. Furthermore, self-fluorescent IR820-hydrogel and CpG nanoparticles exerted the imaging-guided combined photothermal-immunotherapy by the dual fluorescence imaging method without additional fluorescent labeling . This visible combined photothermal-immunotherapy offers a potential for precise cancer treatment.
研究领域:
肿瘤学
·
生物医学工程
·
免疫学
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Jun Zhang,Tiantian Zuo,Jie Yang,Zongwei Hu,Zhihua Wang,Rui Xu,Siyu Ma,Yawen Wei,Qi Shen
The aggressive progression of breast cancer is impacted significantly by the tumor microenvironment (TME). The current chemotherapy normally causes cytotoxicity to tumor cells, while does not effectively modulate the TME. Thus, the chemotherapy effect of breast cancer is usually dissatisfactory. In this study, a kind of hierarchically releasing bio-responsive nanoparticles (R(D)/H(S) NPs), constructed by β-cyclodextrin-grafted heparin and pH-sensitive pseudorotaxane, were investigated to enhance the breast cancer chemotherapeutic efficacy through TME modulation. Doxorubicin (DOX) and transforming growth factor-β (TGF-β) receptor inhibitor (SB431542) loaded onto R(D)/H(S) NPs were released rapidly for the respective response to low pH in endosomes/lysosomes and heparanase (HPSE) in TME. Our results showed that R(D)/H(S) NPs effectively inhibited the formation of tumor-associated fibroblasts (TAFs) and reduced TGF-β and collagen I secretion. Besides, the immunosuppressive microenvironment was effectively reversed into immunogenic, characterized by increased CD8+ and CD4+ T cell infiltration, which distinctly inhibited breast cancer metastasis. Therefore, R(D)/H(S) NPs remodeled the TME by downregulating TAFs, TGF-β, and collagen I; activating the immune microenvironment; and then amplifying the chemotherapeutic efficacy of DOX.
研究领域:
肿瘤学
·
纳米技术
·
药理学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 9
·期 3
·973-984
·
IF 6.183
Ya Wen,Yiqiong Liu,Fangfang Guo,Yi Han,Qiansai Qiu,Yan Li,Haiqing Dong,Tianbin Ren,Yongyong Li
It has been suggested that immunogenic cell death (ICD) has therapeutic potential; however, its anticancer immunity is considerably hampered by the in situ immunosuppressive microenvironment within the tumor area, such as the dysfunction of antigen-presenting cells. Herein, we present an in vitro ICD-inducing modality to circumvent such impairment of immune activation. To this end, a “hot”, i.e., immunogenic, whole tumor cell vaccine is generated in vitro and subcutaneously vaccinated in the normal tissue, departing from the site of the in situ immunosuppressive tumor area, to fully leverage the ICD-inducing antitumor immunity. In particular, the immunogenic dying tumor cells, caged by cellular disulfide–thiol exchange, are mediated by photoactivation. After subcutaneous vaccination, the photoactivated caged live cell vaccine (CLCV) exerts multi-durable immunostimulatory property, which, when adjuvanted by CpG, efficiently promotes dendritic cell (DC) activation and elicits robust CD8+ T-cell responses in vivo. Importantly, the generated T-cell responses are shown to protect 75% mice preimmunized with CLCV against tumor initiation and significantly retards tumor growth in the therapeutic setting. The strategy presented here may help to enrich the current vaccine design for cancer immunotherapy.
研究领域:
癌症免疫治疗
·
免疫学
·
肿瘤学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Yiqiong Liu,Dailin Xu,Ying Liu,Xiao Zheng,Jie Zang,Wanli Ye,Yuge Zhao,Ruiqing He,Shuangrong Ruan,Tingting Zhang,Haiqing Dong,Yan Li,Yongyong Li
Tumor hyaluronan (HA) accumulation is closely associated with the formation of a hypoxic microenvironment that is highly immunosuppressive and severely hinders the efficacy of antitumor therapeutics. To address this problem, we develop an effective HA attenuation strategy that uses an integrated nanosystem based on mesoporous polydopamine (mPDA) with excellent photothermal conversion efficiency to boost hyaluronidase (HAase) activity remotely. Upon light irradiation, the thermal effect generated by mPDA not only directly kills tumor cells that produces an in situ vaccine effect, but also significantly boosts HAase activity (∼5 folds), leading to marked HA break down. Photoheat and HA degradation synergistically reduce tumor HIF-1α expression and reverse immunosuppressive responses. Using the synergistic treatment in a breast cancer model, we find decreased infiltration of immunosuppressive cells, including myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells , increased immune-activated cells, such as mature dendritic cells and CD8 + T cells, and reduced immune checkpoint PD-L1 expression. The resulting relief from tumor microenvironment immunosuppression significantly contributes to an enhanced antitumor effect. This study provides an effective strategy to improve the hypoxic tumor microenvironment and simultaneously promote immune-mediated tumor regression.
研究领域:
癌症生物学
·
免疫治疗
·
纳米技术
·
光热治疗
·
肿瘤微环境
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2023
·
IF 5.8
Siyu Chen,Yicheng Lv,Yue Wang,Deping Kong,Jindong Xia,Jingchao Li,Quan Zhou
Cancer nanomedicine combined with immunotherapy has emerged as a promising strategy for the treatment of cancer. However, precise regulation of the activation of antitumor immunity in targeting tissues for safe and effective cancer immunotherapy remains challenging. Herein, we report a tumor acidic microenvironment-responsive promodulator iron oxide nanoparticle (termed as FGR) with pH-activated action for photothermal-enhanced chemodynamic immunotherapy of cancer. FGR is formed via surface-modifying iron oxide nanoparticles with a dextran-conjugated Toll-like receptor agonist (R848) containing an acid-labile bond. In an acidic tumor microenvironment, the acid-responsive bonds are hydrolyzed to trigger the specific release of R848 to promote the maturation of dendritic cells. In addition, iron oxide nanoparticles within FGR exert photothermal and chemodynamic effects under near-infrared laser irradiation to directly kill tumor cells and induce immunogenic cell death. The synergistic effect of the released immunogenic factors and the acid-activated TLR7/8 pathway stimulates the formation of strong antitumor immunity, resulting in increased infiltration of cytotoxic CD8+ T cells into tumor tissues. As a result, FGR achieves acid-responsive on-demand release and activation of modulators in tumor sites and mediates photothermal-enhanced chemodynamic immunotherapy to inhibit the growth and metastasis of melanoma. Therefore, this work proposes a general strategy for designing prodrug nanomedicines to accurately regulate cancer immunotherapy.
研究领域:
癌症研究
·
纳米技术
·
免疫疗法
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2023
·
IF 6
Yuan Gao,Yingxi Zhang,Hong Xia,Yuqing Ren,Haibin Zhang,Siwen Huang,Meiju Li,Yongjun Wang,Heran Li,Hongzhuo Liu
Nanocarrier antigen-drug delivery system interacts specifically with immune cells and provides intelligent delivery modes to improve antigen delivery efficiency and facilitate immune progression. However, these nanoparticles often have weak adhesion to cells, followed by insufficient cell absorption, leading to a failed immune response. Inspired by the structure and function of viruses, virus-like mesoporous silica nanoparticles (VMSNs) were prepared by simulating the surface structure, centripetal-radialized spike structure and rough surface topology of the virus and co-acted with the toll-like receptor 7/8 agonist imiquimod (IMQ) and antigens oocyte albumin (OVA). Compared to the conventional spherical mesoporous silica nanoparticles (MSNs), VMSNs which was proven to be biocompatible in both cellular and in vivo level, had higher cell invasion ability and unique endocytosis pathway that was released from lysosomes and promoted antigen cross-expression. Furthermore, VMSNs effectively inhibited B16-OVA tumor growth by activating DCs maturation and increasing the proportion of CD8+ T cells. This work demonstrated that virus-like mesoporous silica nanoparticles co-supply OVA and IMQ, could induce potent tumor immune responses and inhibit tumor growth as a consequence of the surface spike structure induces a robust cellular immune response, and undoubtedly provided a good basis for further optimizing the nanovaccine delivery system.
研究领域:
纳米技术
·
生物医学工程
·
免疫学
·
癌症研究
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Jiawen He,Ruixiang Song,Fengfeng Xiao,Meng Wang,Liewei Wen
Purpose Photothermal therapy (PTT) is a promising anticancer treatment that involves inducing thermal ablation and enhancing antitumor immune responses. However, it is difficult to completely eradicate tumor foci through thermal ablation alone. Additionally, the PTT elicited antitumor immune responses are often insufficient to prevent tumor recurrence or metastasis, due to the presence of an immunosuppressive microenvironment. Therefore, combining photothermal and immunotherapy is believed to be a more effective treatment approach as it can modulate the immune microenvironment and amplify the post-ablation immune response.Methods Herein, the indoleamine 2, 3‐dioxygenase‐1 inhibitors (1-MT) loaded copper (I) phosphide nanocomposites (Cu3P/1-MT NPs) are prepared for PTT and immunotherapy. The thermal variations of the Cu3P/1-MT NPs solution under different conditions were measured. The cellular cytotoxicity and immunogenic cell death (ICD) induction efficiency of Cu3P/1-MT NPs were analyzed by cell counting kit-8 assay and flow cytometry in 4T1 cells. And the immune response and antitumor therapeutic efficacy of Cu3P/1-MT NPs were evaluated in 4T1-tumor bearing mice.Results Even at low energy of laser irradiation, Cu3P/1-MT NPs remarkably enhanced PTT efficacy and induced immunogenic tumor cell death. Particularly, the tumor-associated antigens (TAAs) could help promote the maturation of dendritic cells (DCs) and antigen presentation, which further activates infiltration of CD8+ T cells through synergistically inhibiting the indoleamine 2, 3‐dioxygenase‐1. Additionally, Cu3P/1-MT NPs decreased the suppressive immune cells such as regulatory T cells (Tregs) and M2 macrophages, indicating an immune suppression modulation effect.Conclusion Cu3P/1-MT nanocomposites with excellent photothermal conversion efficiency and immunomodulatory properties were prepared. In addition to enhanced the PTT efficacy and induced immunogenic tumor cell death, it also modulated the immunosuppressive microenvironment. Thereby, this study is expected to offer a practical and convenient approach to amplify the antitumor therapeutic efficiency with photothermal-immunotherapy.
研究领域:
肿瘤学
·
纳米技术
·
免疫疗法
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Qingyan Zhang,Pengkai Wu,Jicheng Wu,Hao Shou,Xinliang Ming,Shuqi Wang,Ben Wang
Classical chemotherapeutic drugs may cause immunogenic cell death (ICD), followed by activating CD8+ T cells to promote cell-mediated antitumor immune responses. However, CD8+ T cells become exhausted due to tumor antigens’ continuous stimulation, creating a major obstacle to effectively suppressing tumor growth and metastasis. Here, we develop an approach of chemo-gene combinational nanomedicine to bridge and reprogram chemotherapy and immunotherapy. The dually loaded nanomedicine induces ICD in tumor cells through doxorubicin and reverses the antitumor effects of exhausted CD8+ T cells through the small interfering RNA. The synergistic chemo-gene and fluorine assembly nanomedicine enriched in reactive oxygen species and acid-sensitive bonds results in enhanced cancer immunotherapy to inhibit tumor growth and the lung metastasis of breast cancer in a mouse model of breast cancer and melanoma. This study provides an efficient strategy and insights into chemoimmunological cascade therapy for combating malignant metastatic tumors.
研究领域:
癌症生物学
·
纳米技术
·
免疫治疗
·
药学
✓ 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）