Enhanced Cellular Ablation by Attenuating Hypoxia Status and Reprogramming Tumor-Associated Macrophages via NIR Light-Responsive Upconversion Nanocrystals
Enhanced Cellular Ablation by Attenuating Hypoxia Status and Reprogramming Tumor-Associated Macrophages via NIR Light-Responsive Upconversion Nanocrystals
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DOI：
10.1021/acs.bioconjchem.8b00068
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发表时间：
2018-04-01
影响因子：
4.7
通讯作者：
Xing, Bengang
中科院分区：
文献类型：
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作者：
Ai, Xiangzhao;Hu, Ming;Xing, Bengang
近红外（NIR）光动力疗法（PDT），特别是基于镧系掺杂的上转换纳米晶体（ucn），由于其独特的光学特性，将近红外光激发转化为多个短波长的发射，作为一种有前途的有效细胞消融策略，已被广泛研究。尽管近红外能穿透深层组织。在生命系统中，缺氧肿瘤微环境中氧气供应不足，极大地限制了其治疗效果。此外，共存的肿瘤相关巨噬细胞（tam）在pdt后的肿瘤复发中起着关键作用。在此，我们通过整合二氧化锰（MnO2）纳米片和透明质酸（HA）生物聚合物，开发了一种独特的光敏剂负载的UCNs纳米共轭物（PUN），通过减弱缺氧状态和协同重编程tam种群来提高近红外光介导的PDT效果。在酸性肿瘤微环境下与过量产生的H2O2反应后，MnO2纳米片在808 nm近红外光照射下降解生成大量氧气，大大提高了氧依赖型PDT效率。更重要的是，生物激发聚合物HA可以有效地将促肿瘤m2型tam的极化重编程为抗肿瘤ml型巨噬细胞，从而防止PDT治疗后肿瘤复发。这些有希望的结果为通过减弱低氧肿瘤微环境，在近红外光介导的PDT治疗中实现增强细胞消融提供了巨大的机会，从而促进了新一代纳米平台的合理设计，用于免疫治疗，以抑制PDT后时期的肿瘤复发。
Near-infrared (NIR) light-mediated photodynamic therapy (PDT), especially based on lanthanide-doped upconversion nanocrystals (UCNs), have been extensively investigated as a promising strategy for effective cellular ablation owing to their unique optical properties to convert NIR light excitation into multiple short-wavelength emissions. Despite the deep tissue penetration of NIR. light in living systems, the therapeutic efficiency is greatly restricted by insufficient oxygen supply in hypoxic tumor microenvironment. Moreover, the coexistent tumor-associated macrophages (TAMs) play critical roles in tumor recurrence during the post-PDT period. Herein, we developed a unique photo sensitizer-loaded UCNs nanoconjugate (PUN) by integrating manganese dioxide (MnO2) nanosheets and hyaluronic acid (HA) biopolymer to improve NIR light-mediated PDT efficacy through attenuating hypoxia status and synergistically reprogramming TAMs populations. After the reaction with overproduced H2O2 in acidic tumor microenvironment, the MnO2 nanosheets were degraded for the production of massive oxygen to greatly enhance the oxygen-dependent PDT efficiency upon 808 nm NIR light irradiation. More importantly, the bioinspired polymer HA could effectively reprogram the polarization of pro-tumor M2-type TAMs to anti-tumor Ml-type macrophages to prevent tumor relapse after PDT treatment. Such promising results provided the great opportunities to achieve enhanced cellular ablation upon NIR light-mediated PDT treatment by attenuating hypoxic tumor microenvironment, and thus facilitated the rational design of new generations of nanoplatforms toward immunotherapy to inhibit tumor recurrence during post-PDT period.