Tumor Microenvironment Responsive Drug-Dye-Peptide Nanoassembly for Enhanced Tumor-Targeting, Penetration, and Photo-Chemo-Immunotherapy
Tumor Microenvironment Responsive Drug-Dye-Peptide Nanoassembly for Enhanced Tumor-Targeting, Penetration, and Photo-Chemo-Immunotherapy
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肿瘤微环境响应性药物-染料-肽纳米组装体用于增强肿瘤靶向、渗透和光化学免疫治疗
DOI：
10.1002/adfm.201900004
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发表时间：
2019-05-09
影响因子：
19
通讯作者：
Qian, Zhiyong
中科院分区：
文献类型：
--
作者：
Peng, Jinrong;Yang, Qian;Qian, Zhiyong
由治疗学构建的纳米医学在生物医学应用中，特别是在癌症治疗的药物输送方面具有独特的、不可替代的优势。然而，用于构建具有肿瘤微环境因素响应性的基于治疗的纳米药物的策略仍然很复杂。在本研究中，使用易于操作的程序构建了一种基于治疗的纳米系统，该系统具有主动肿瘤靶向、增强渗透和刺激响应性药物释放行为以及程序性细胞死亡-1/程序性细胞死亡-配体1（PD-1/PD-L1）阻断介导的免疫调节，以增强肿瘤免疫治疗。含有Lyp-1序列的基质金属蛋白酶2响应肽有助于主动肿瘤靶向的成功和增强纳米颗粒在肿瘤组织中的渗透。所获得的纳米系统在前24小时内显着抑制原发性肿瘤生长（97.5%以上的肿瘤细胞被抑制），并且与光热治疗相结合可以实现完全抑制。 IR820作为治疗的载体，用作光热治疗的光敏剂。作为 PD-1/PD-L1 阻断拮抗剂的 d 肽进一步减轻了远端肿瘤的进展和侵袭。因此，提供了一种治疗学构建的多功能纳米系统来实现组合治疗策略以增强治疗效果。
Nanomedicine constructed by therapeutics has unique and irreplaceable advantages in biomedical applications, especially in drug delivery for cancer therapy. The strategy, however, used to construct the therapeutics-based nanomedicines with tumor microenvironmental factor responsiveness is still sophisticated. In this study, an easy-operating procedure is used to construct a therapeutics-based nanosystem with active tumor-targeting, enhanced penetration, and stimuli-responsive drug release behavior as well as programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) blockading mediated immunomodulation to enhance tumor immunotherapy. The matrix metalloproteinase-2 responsive peptide with the existence of Lyp-1 sequence contributes to the success of active tumor-targeting and the enhancement of the penetration of the nanoparticles in tumor tissue. The obtained nanosystem strikingly inhibits the primary tumor growth in the first 24 h (more than 97.5% of tumor cells are inhibited), and total inhibition can be achieved with the combination of photothermal therapy. IR820, which is served as the carrier for the therapeutics, is used as a photosensitizer for photothermal therapy. The progress and aggression of distal tumor has further been alleviated by a d-peptide which is an antagonist for PD-1/PD-L1 blockage. Therefore, a therapeutics-constructed multifunctional nanosystem is provided to realize a combinational therapeutic strategy to enhance the therapeutic outcome.