Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry , Wuhan University , Wuhan 430072 , P.R. China.
Institute for Advanced Studies (IAS) , Wuhan University , Wuhan 430072 , P.R. China.
ACS Nano. 2019 May 28;13(5):5523-5532. doi: 10.1021/acsnano.9b00345. Epub 2019 May 6.
Carbon monoxide (CO) is regarded as a potential therapeutic agent with multiple beneficial functions for biomedical applications. In this study, a versatile CO nanogenerator (designated as PPOSD) was fabricated and developed for tumor therapy and anti-inflammation. Partially oxidized tin disulfide (SnS) nanosheets (POS NSs) were decorated with a tumor-targeting polymer (polyethylene glycol-cyclo(Asp-d-Phe-Lys-Arg-Gly), PEG-cRGD), followed by the loading of chemotherapeutic drug doxorubicin (DOX) to prepare polymer@POS@DOX, or PPOSD. After injected intravenously, PPOSD could selectively accumulate in tumor tissue via the cRGD-mediated tumor recognition. Upon 561 nm laser irradiation, the POS moiety in PPOSD can photoreduce CO to CO, which significantly sensitized the chemotherapeutic effect of DOX. The POS in PPOSD can also act as a photothermal agent for effective photothermal therapy (PTT) of the tumor upon 808 nm laser irradiation. Furthermore, the generated CO can simultaneously decrease the inflammatory reaction caused by PTT. Blood analysis and hematoxylin-eosin staining of major organs showed that no obvious systemic toxicity was induced after the treatment, suggesting good biosafety of PPOSD. This versatile CO nanogenerator will find great potential for both enhanced tumor inhibition and anti-inflammation.
一氧化碳（CO）被认为是一种具有多种有益功能的潜在治疗剂，可应用于生物医学领域。在本研究中，我们制备并开发了一种多功能 CO 纳米发电机（命名为 PPOSD），用于肿瘤治疗和抗炎。部分氧化的二硫化锡（SnS）纳米片（POS NSs）被肿瘤靶向聚合物（聚乙二醇-环（Asp-d-Phe-Lys-Arg-Gly），PEG-cRGD）修饰，然后负载化疗药物阿霉素（DOX），制备聚合物@POS@DOX，或 PPOSD。静脉注射后，PPOSD 可以通过 cRGD 介导的肿瘤识别选择性地积聚在肿瘤组织中。在 561nm 激光照射下，PPOSD 中的 POS 部分可以将 CO 光还原为 CO，这显著增强了 DOX 的化疗效果。PPOSD 中的 POS 部分也可以作为光热剂，在 808nm 激光照射下有效进行肿瘤光热治疗（PTT）。此外，产生的 CO 还可以同时减轻 PTT 引起的炎症反应。血液分析和主要器官的苏木精-伊红染色表明，治疗后没有明显的全身毒性，表明 PPOSD 具有良好的生物安全性。这种多功能 CO 纳米发电机将在增强肿瘤抑制和抗炎方面具有巨大的应用潜力。
