Department of Chemistry , Northeastern University , 110004 Shenyang , China.
ACS Appl Mater Interfaces. 2019 May 15;11(19):17215-17225. doi: 10.1021/acsami.9b02484. Epub 2019 May 1.
As a highly oxygen-dependent process, the effect of photodynamic therapy is often obstructed by the premature leakage of photosensitizers and the lack of oxygen in hypoxic cancer cells. To overcome these limitations, this study designs bovine serum albumin protein (BSA)-encapsulated Pt nanoclusters (PtBSA) as O-supplied biocoats and further incorporates them with mesoporous silica nanospheres to develop intelligent nanoaggregates for achieving improved therapeutic outcomes against hypoxic tumors. The large number of amino groups on BSA can provide sufficient functional groups to anchor tumor targeting agents and thus enhance the selective cellular uptake efficiency. Owing to the outstanding biocompatibility features of BSA and the state-of-the-art catalytic activity of Pt nanoclusters, the nanocomposites have lower dark cytotoxicity, and O continuously evolves via the decomposition of HO in a tumor microenvironment. Both in vivo and in vitro experiments indicate that the resulting nanocomposites can effectively relieve hypoxic conditions, specifically induce necrotic cell apoptosis, and remarkably hinder tumor growth. Our results illuminate the great potential of BSA-encapsulated Pt nanoclusters as versatile biocoats in designing intelligent nanocarriers for hypoxic-resistant photodynamic therapy.
作为一个高度依赖氧气的过程，光动力疗法的效果常常受到光敏剂的过早泄漏和缺氧癌细胞中氧气缺乏的阻碍。为了克服这些限制，本研究设计了牛血清白蛋白蛋白（BSA）包裹的 Pt 纳米团簇（PtBSA）作为供氧生物涂层，并进一步将其与介孔硅纳米球结合，开发智能纳米聚集体，以实现对缺氧肿瘤的治疗效果的改善。BSA 上大量的氨基可为肿瘤靶向剂提供足够的功能基团，从而提高选择性细胞摄取效率。由于 BSA 的出色生物相容性和 Pt 纳米团簇的最先进的催化活性，纳米复合材料具有较低的暗毒性，并且 O 通过肿瘤微环境中 HO 的分解不断演化。体内和体外实验均表明，所得纳米复合材料可有效缓解缺氧状态，特异性诱导坏死细胞凋亡，并显著抑制肿瘤生长。我们的结果表明，BSA 包裹的 Pt 纳米团簇作为多功能生物涂层，在设计用于耐缺氧光动力疗法的智能纳米载体方面具有巨大的潜力。
