National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan 430074, China.
School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, China.
ACS Appl Mater Interfaces. 2017 Jul 19;9(28):23564-23573. doi: 10.1021/acsami.7b08047. Epub 2017 Jul 10.
Ideal anticancer nano drug delivery systems (NDDSs) need to overcome a series of physiological barriers including blood circulation, tumor accumulation, tumor penetration, internalization by cancer cells, lysosomal escape, and on-demand intracellular drug release following systemic administration. However, it remains a big challenge to construct NDDSs that can overcome all the barriers at the same time. Here, we develop zwitterionic temperature/redox-sensitive nanogels loaded with near-infrared (NIR) dye Indocyanine green (ICG) and anticancer drug doxorubicin (I/D@NG). I/D@NG exhibits enhanced photothermal effects, and NIR irradiation markedly decreases its diameter. NIR irradiation at tumor sites significantly enhances tumor accumulation, tumor penetration, and cellular uptake of I/D@NG with prolonged blood circulation time. Furthermore, I/D@NG can effectively escape from lysosomes by singlet oxygen-induced lysosomal disruption, and DOX is then sufficiently released from the nanogels to the nucleus in response to high intracellular GSH and photothermal effects. This nanoplatform for thermo-chemotherapy not only efficiently exerts synergistic cytotoxicity but also overcomes all the physiological barriers of therapeutic agent, thereby providing a substantial in vivo anticancer effect. The multiple functions of I/D@NG provide new insights into designing nanoplatforms for synergistic cancer therapy.
理想的抗癌纳米药物传递系统（NDDS）需要克服一系列生理屏障，包括血液循环、肿瘤积累、肿瘤穿透、癌细胞内化、溶酶体逃逸以及系统给药后的按需细胞内药物释放。然而，构建能够同时克服所有这些障碍的 NDDS 仍然是一个巨大的挑战。在这里，我们开发了载有近红外（NIR）染料吲哚菁绿（ICG）和抗癌药物阿霉素（I/D@NG）的两性离子温度/氧化还原敏感纳米凝胶。I/D@NG 表现出增强的光热效应，并且近红外辐射显著降低其直径。在肿瘤部位的近红外辐射显著增强了 I/D@NG 的肿瘤积累、肿瘤穿透和细胞摄取，同时延长了血液循环时间。此外，I/D@NG 可以通过单线态氧诱导的溶酶体破坏有效地从溶酶体中逃逸，并且 DOX 随后从纳米凝胶中充分释放到细胞核中，以响应细胞内高 GSH 和光热效应。这种用于热化疗的纳米平台不仅有效地发挥协同细胞毒性作用，而且克服了治疗剂的所有生理屏障，从而提供了显著的体内抗癌效果。I/D@NG 的多种功能为设计协同癌症治疗的纳米平台提供了新的思路。
