Tumor Microenvironment Responsive Drug‐Dye‐Peptide Nanoassembly for Enhanced Tumor‐Targeting, Penetration, and Photo‐Chemo‐Immunotherapy,Advanced Functional Materials

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Tumor Microenvironment Responsive Drug‐Dye‐Peptide Nanoassembly for Enhanced Tumor‐Targeting, Penetration, and Photo‐Chemo‐Immunotherapy
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2019-03-20 , DOI: 10.1002/adfm.201900004
Jinrong Peng ₁ , Qian Yang _{1,

2} , Yao Xiao ₁ , Kun Shi ₁ , Qingya Liu ₁ , Ying Hao ₁ , Fan Yang ₁ , Ruxia Han ₁ , Zhiyong Qian ₁

Affiliation

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.

中文翻译：

肿瘤微环境响应性药物-染料-肽纳米组件，用于增强肿瘤靶向，穿透和光化学免疫治疗。

由治疗剂构建的纳米医学在生物医学应用中具有独特且不可替代的优势，尤其是在用于癌症治疗的药物输送中。然而，用于构建具有肿瘤微环境因子反应性的基于治疗剂的纳米药物的策略仍然很复杂。在这项研究中，使用了一种易于操作的程序来构建基于治疗的纳米系统，该系统具有主动靶向肿瘤，增强的渗透性和刺激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，以增强肿瘤免疫疗法。具有Lyp-1序列的基质金属蛋白酶-2响应肽有助于成功靶向肿瘤，并增强纳米颗粒在肿瘤组织中的渗透。所获得的纳米系统在最初的24小时内显着抑制了原发性肿瘤的生长（超过97.5％的肿瘤细胞被抑制），并且通过光热疗法的组合可以实现完全抑制。用作治疗剂的载体IR820用作光热疗法的光敏剂。远端肿瘤的进展和侵袭进一步缓解了。用作治疗剂的载体，用作光热疗法的光敏剂。远端肿瘤的进展和侵袭进一步缓解了。用作治疗剂的载体，用作光热疗法的光敏剂。远端肿瘤的进展和侵袭进一步缓解了。d-肽，是PD-1 / PD-L1阻断剂的拮抗剂。因此，提供了一种由治疗剂构建的多功能纳米系统，以实现增强治疗效果的组合治疗策略。

更新日期：2019-03-20

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