Du Huan, Wang Fang, Zhang Ruyan, Ma Yan, Huo Xiaobing, Ning Gan, Wang Xiufeng, Zhou Ting, Zhang Guodong, Zhang Zhiqing
College of Chemistry and Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China.
College of Chemistry and Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China.
J Inorg Biochem. 2025 Apr;265:112831. doi: 10.1016/j.jinorgbio.2025.112831. Epub 2025 Jan 17.
Developing multifunctional nanomedicines represents a frontier. We have engineered a high-capacity DNA vector basing rolling circle amplification for the delivery of copper sulfide nanoparticles (CuS NPs) and doxorubicin (DOX), coupled with multivalent aptamers (MA) that precisely target tumors, culminating in a multifunctional nanoplatform (RMALCu@DOX), which combines the chemotherapy (CT)/photothermal therapy (PTT)/chemodynamic therapy (CDT). The vector (RMAL) boasts exceptional biocompatibility and incorporates multiple copy units, enabling the precise loading of numerous CuS NPs, forming RMALCu which possesses a robust photothermal effect and superior Fenton-like catalytic activity, heralding a project of minimally invasive dual-mode (PTT/CDT) therapy. Furthermore, the abundance of G-C of RMAL enabled effective DOX encapsulation through π-π interactions to construct RMALCu@DOX. The MA integrated into RMALCu@DOX is pivotal in enhancing the targeting of tumors and in preventing non-specific release of CuS and DOX, enabling an integrated CT/PTT/CDT. Data indicate that 1 nM of RMALCu could load 270 nM of DOX with an impressive loading capacity of 77 %, and modification with MA, its tumor-targeting ability was amplified by 51-fold and significantly bolstered in vitro imaging outcomes, and the synergistic killing of B16 was as 67.3 %. This innovative nanoplatform offers a comprehensive and holistic strategy for the treatment of malignant tumors.
开发多功能纳米药物是一个前沿领域。我们设计了一种基于滚环扩增的高容量DNA载体，用于递送硫化铜纳米颗粒（CuS NPs）和阿霉素（DOX），并结合了精确靶向肿瘤的多价适配体（MA），最终形成了一种多功能纳米平台（RMALCu@DOX），它结合了化疗（CT）/光热疗法（PTT）/化学动力学疗法（CDT）。该载体（RMAL）具有出色的生物相容性并包含多个复制单元，能够精确负载大量CuS NPs，形成具有强大光热效应和优异类芬顿催化活性的RMALCu，开创了微创双模式（PTT/CDT）治疗方案。此外，RMAL丰富的G-C通过π-π相互作用实现了有效的DOX包封，从而构建了RMALCu@DOX。整合到RMALCu@DOX中的MA对于增强肿瘤靶向性以及防止CuS和DOX的非特异性释放至关重要，从而实现了CT/PTT/CDT的整合。数据表明，1 nM的RMALCu能够负载270 nM的DOX，负载能力高达77%，经MA修饰后，其肿瘤靶向能力提高了51倍，并显著增强了体外成像效果，对B16的协同杀伤率为67.3%。这种创新的纳米平台为恶性肿瘤的治疗提供了一种全面且整体的策略。
