ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Qi Shang,Shiyao Zhou,Yue Jiang,Dong Wang,Jiqian Wang,Aixin Song,Yuxia Luan
Immune checkpoint blockade of the programmed cell death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pathway via an antibody is a potent strategy for T cell remodeling. Nevertheless, the potency of the antibody is partly compromised by its high price, instability, risk of autoimmune disease, and so forth. Small-molecule inhibitors are interesting alternatives to antibodies. However, tumor-specific delivery of small-molecule inhibitors to the target site for boosting the interruption of the PD-L1/PD-1 pathway is rarely reported. Herein, we designed a tumor-specific delivery nanoplatform that could efficiently deliver the small-molecule inhibitor to the precise target site, greatly enhancing the blocking effect of the PD-L1/PD-1 pathway. Hyaluronic acid (HA) was conjugated with chlorin e6 (Ce6), resulting in a HA–Ce6 conjugate (HC). The nanoplatform was constructed by the HC micelles with the encapsulation of small-molecule inhibitor, BMS 202 (BMS), to form BMS/HC micelles. The target property of HA, combined with the hyaluronidase-induced degradation of HA in the tumor site, enables the as-prepared micelles with tumor-specific delivery of BMS for blocking the PD-L1/PD-1 pathway. With cooperative treatment with the photosensitizer Ce6, the present therapeutic nanoplatform demonstrated excellent photoimmunotherapy for tumor regression in distant tumors and lung metastasis. This strategy of tumor-specific delivery of small-molecule inhibitors provides an effective pathway to strengthen the blocking efficacy of PD-L1/PD-1 on effective photoimmunotherapy.
研究领域:
癌症研究
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免疫疗法
·
纳米医学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yaqing Kang,Jiao Yan,Xiaoqing Han,Xingbo Wang,Yanjing Wang,Panpan Song,Xiaochen Su,Abdur Rauf,Xuefei Jin,Fang Pu,Haiyuan Zhang
Cancer immunotherapy is developing as the mainstream strategy for treatment of cancer. However, the interaction between the programmed cell death protein-1 (PD-1) and the programmed death ligand 1 (PD-L1) restricts T cell proliferation, resulting in the immune escape of tumor cells. Recently, immune checkpoint inhibitor therapy has achieved clinical success in tumor treatment through blocking the PD-1/PD-L1 checkpoint pathway. However, the presence of M2 tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) will inhibit antitumor immune responses and facilitate tumor growth, which can weaken the effectiveness of immune checkpoint inhibitor therapy. The repolarization of M2 TAMs into M1 TAMs can induce the immune response to secrete proinflammatory factors and active T cells to attack tumor cells. Herein, hollow iron oxide (Fe3O4) nanoparticles (NPs) were prepared for reprogramming M2 TAMs into M1 TAMs. BMS-202, a small-molecule PD-1/PD-L1 inhibitor that has a lower price, higher stability, lower immunogenicity, and higher tumor penetration ability compared with antibodies, was loaded together with pH-sensitive NaHCO3 inside hollow Fe3O4 NPs, followed by wrapping with macrophage membranes. The formed biomimetic FBN@M could produce gaseous carbon dioxide (CO2) from NaHCO3 in response to the acidic TME, breaking up the macrophage membranes to release BMS-202. A series of in vitro and in vivo assessments revealed that FBN@M could reprogram M2 TAMs into M1 TAMs and block the PD-1/PD-L1 pathway, which eventually induced T cell activation and the secretion of TNF-α and IFN-γ to kill the tumor cells. FBN@M has shown a significant immunotherapeutic efficacy for tumor treatment.
研究领域:
生物医学工程
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肿瘤免疫学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2025
·
IF 5.1
Sha Liu,Lina Wang,Yupeng Wang,Lina Geng
Delayed healing of post-melanoma-resection wounds is prone to induce tumor recurrence. Therefore, postoperative wound management for tumor resection needs concurrently address anti-cancer activity and wound healing promotion. In this study, a multifunctional micelle-hydrogels (AB@MH) was fabricated by integrating reactive oxygen species (ROS)-responsive nanomicelles, which co-loaded with apigenin and BMS-202, into dodecyl-modified chitosan (DCS) based hydrogel via Schiff base linkages and hydrogen bonding interactions, for post-resection melanoma therapy. This micelle-hydrogel enables ROS-triggered drug release, thereby minimizing systemic toxicity. More importantly, the released apigenin exerts selective cytotoxicity against tumor cells and bacteria while inducing immunogenic cell death (ICD). When combined with co-released BMS-202, the formulation enhances anti-tumor efficacy without harming normal tissue cells. Moreover, the AB@MH is fabricated via a straightforward, crosslinker-free method, ensuring excellent biocompatibility and effective wound healing promotion. In the melanoma resection model, the AB@MH group exhibited marked suppression of tumor recurrence and accelerated wound repair. This work successfully integrates post-resection antitumor therapy and wound healing enhancement, achieving both safety and efficacy in postoperative cancer therapy.
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 15
·4140-4155
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IF 7.59
Yingping Zeng,Tong Yu,Shufen Zhang,Guangtao Song,Tingting Meng,Hong Yuan,Fuqiang Hu
Tumor vessel normalization can alleviate hypoxia, reduce the intratumoral infiltration of immunosuppressive cells and increase the intratumoral infiltration of immune effector cells (CD8+ T cells), further reversing the immunosuppressive microenvironment. Here, nanocomplexes (lipo/St@FA–COSA/BMS-202) which can accurately deliver drugs to tumor tissues and release different drugs at different sites with different rates were prepared to combine tumor vessel normalization with immune checkpoint blockade. The results of drug release in vitro showed that in a pH 6.5 release medium, lipo/St@FA–COSA/BMS-202 rapidly released the vascular normalizing drug (sunitinib, St) and slowly released the PD-1/PD-L1-blocking drug (BMS-202). The results of in vivo experiments showed that the rapidly released St normalized tumor vessels and formed an immunosupportive microenvironment which improved the anti-tumor efficacy of BMS-202. In conclusion, the drug delivery strategy significantly inhibited tumor growth and had excellent anti-tumor efficacy, which can provide a potential approach for effective tumor treatment.
研究领域:
肿瘤学
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药学
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纳米技术
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免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Yingli Wang,Jiang Yu,Dan Li,Liwen Zhao,Bingjun Sun,Jiamei Wang,Zhenjie Wang,Shuang Zhou,Menglin Wang,Yinxian Yang,Hongzhuo Liu,Haotian Zhang,Qingzhi Lv,Qikun Jiang,Zhonggui He,Yongjun Wang
The combination of chemotherapy with the immune checkpoint blockade (ICB) therapy is bringing a tremendous hope in the treatment of malignant tumors. However, the treatment efficacy of the existing chemo-immunotherapy is not satisfactory due to the high cost and immunogenicity of ICB antibodies, low response rate to ICB, off-target toxicity of therapeutic agents, and low drug co-delivery efficacy. Therefore, a high-efficient nanosystem combining the delivery of chemotherapeutics with small molecule ICB inhibitors may be promising for an efficient cancer therapy. Herein, a novel reactive oxygen species (ROS)-activated liposome nanoplatform was constructed by the loading of a ROS-sensitive paclitaxel derivative (PSN) into liposomes to overcome the difficulties on delivering paclitaxel mostly represented by premature drug release and a low amount accumulated into the tumor. The innovative liposomal nanosystem was rationally designed by a remote loading of BMS-202 (a small molecule PD-1/PD-L1 inhibitor) and PSN into the liposomes for a ROS-sensitive paclitaxel release and sustained BMS-202 release. The co-loaded liposomes resulted in a high co-loading ability and improved pharmacokinetic properties. An orthotopic 4 T1 breast cancer model was used to evaluate the efficiency of our nanoplatform in vivo, resulting in a superior antitumor activity . The antitumor immunity was activated by paclitaxel-mediated immunogenic cell death , while BMS-202 continuously blocked PD-L1 which could be up-regulated by paclitaxel in tumors to increase the response to ICB and further recover the host immune surveillance. These results revealed that this dual-delivery liposome might provide a promising strategy for a high-efficient chemo-immunotherapy, exhibiting a great potential for clinical translation.
研究领域:
癌症治疗
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纳米技术
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药学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2022
·
IF 18.962
Di Liu,Hongliang He,Fei Kong,Yixiang Cao,Fengchao Zang,Ming Ma,Ning Gu,Yu Zhang
Currently, multimodal synergistic nanoplatform emerges as an important cancer therapy paradigm, however, multimodal synergistic theranostic nanoplatform remains to be developed. Herein, using the mouse model of breast cancer, a versatile multimodal synergistic theranostic nanoplatform is rationally designed and synthesized for enhancing chemodynamic therapy (CDT), overcoming immunosuppression within tumor microenvironment , and inhibiting metastasis as well as tracking tumor. To fulfill our design, a composite Fe/Mn magnetic nanoparticle is first synthesized by loading with Fe 3 O 4 and BMS-202 (PD-L1 inhibitor) within a poly(lactide-co-glycolide)-based nanoparticle core, which are further modified with in situ synthesis of MnO 2 layer. Then, the composite metal-organic nanoparticle is coated with two targeting moieties hyaluronic acid (HA) and AMD3100 (CXCR4 antagonist), respectively, to achieve the multimodal synergistic theranostic nanoplatform ( [email protected] +AMD). With surface targeting modification, [email protected] +AMD exhibits enhanced tumor accumulation, where it effectively consumes endogenous glutathione to generate Mn 2+ allowing for the enhanced CDT effect, alleviates tumor hypoxia by O 2 generation and reverses the tumor immunosuppression. [email protected] +AMD blocks CXCR4 receptor on cancer cells, thus suppressing the CXCR4-mediated cancer metastasis and invasion. Additionally, [email protected] +AMD would synchronously be achieving tumor tracking by T 1 -T 2 dual-mode magnetic resonance imaging. Collectively, this strategy holds a novel multimodal synergistic theranostics for effective cancer management.
研究领域:
纳米技术
·
癌症治疗
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医学成像
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免疫疗法
·
药物递送系统
✓ 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）