School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, PR China.
School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, PR China.
J Control Release. 2021 Jul 10;335:59-74. doi: 10.1016/j.jconrel.2021.05.013. Epub 2021 May 14.
Novel platforms for cisplatin delivery with a controllable manner and combinable with other treatment modality to achieve synergistic antitumor effect and inhibition metastasis for treatment of triple negative breast cancer (TNBC) are highly desirable. Herein, we report a black phosphorus (BP) nanosheets-based nano-assembly which consists of cisplatin, BP, polydopamine (PDA) and hyaluronic acid (HA), cisplatin/BP/PDA-HA (CBPH), for controlled delivery of cisplatin and inhibition tumor growth as well as lung metastasis of TNBC. For constructing CBPH, the surface of BP was dual modified by PDA and HA, resulting in enhanced stability, tumor target ability and photothermal efficiency of BP. Cisplatin was released in response both to internal and external stimuli existed in tumor microenvironment, including low pH, hydrogen peroxide and NIR light, as accompanied by decomposition of BP. In vitro experiments demonstrated CBPH-treated 4 T1 cells showed elevated intracellular content of Pt and Pt-DNA adduct, which was further improved when exposure to NIR light, leading to potent antitumor effect in a synergistic pattern. Anti-metastasis studies in 2D monolayers and 3D organoids revealed that CBPH plus NIR light treatment exhibited significantly decreased migration, invasion and regrowth ability of 4 T1 cells. Furthermore, TNBC-bearing mice with systemic administrate of CBPH showed enhanced tumor accumulation of cisplatin and light-triggered inhibition of tumor growth at primary site and lung metastasis, with alleviated toxicity. But CBPH is yet to be optimized for realizing smart cisplatin delivery in response to acidic and redox stimuli in vivo. Collectively, our study demonstrates that this novel BP-based nano-assembly with controllable tumor delivery of cisplatin and metastasis inhibition of breast cancer expand the use of BP in biomedicine field and hold great promise for further development.
用于顺铂递送的新型平台以可控的方式与其他治疗方式相结合，以实现协同抗肿瘤作用和抑制转移，用于治疗三阴性乳腺癌（TNBC）是非常需要的。本文报道了一种基于黑磷（BP）纳米片的纳米组装体，由顺铂、BP、聚多巴胺（PDA）和透明质酸（HA）组成，用于顺铂的控制释放以及抑制 TNBC 的肿瘤生长和肺转移。为了构建 CBPH，BP 的表面通过 PDA 和 HA 进行双重修饰，从而提高了 BP 的稳定性、肿瘤靶向能力和光热效率。顺铂在响应肿瘤微环境中存在的内部和外部刺激时释放，包括低 pH 值、过氧化氢和 NIR 光，同时伴随着 BP 的分解。体外实验表明，CBPH 处理的 4T1 细胞显示出升高的细胞内 Pt 含量和 Pt-DNA 加合物，当暴露于 NIR 光时进一步提高，从而以协同方式发挥强大的抗肿瘤作用。在 2D 单层和 3D 类器官中的抗转移研究表明，CBPH 加 NIR 光处理表现出显著降低的 4T1 细胞迁移、侵袭和再生长能力。此外，全身性给予 CBPH 的 TNBC 荷瘤小鼠显示出增强的顺铂肿瘤积累和光触发的原发性肿瘤生长和肺转移抑制，同时减轻了毒性。但 CBPH 仍有待优化，以实现体内对酸性和氧化还原刺激的智能顺铂递送。总之，我们的研究表明，这种新型基于 BP 的纳米组装体具有可控的肿瘤递送顺铂和抑制乳腺癌转移的作用，扩展了 BP 在生物医学领域的应用，并为进一步发展提供了巨大的潜力。
