College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350108, China.
CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Key Laboratory of Nanomaterials, and State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, China.
Adv Healthc Mater. 2024 Apr;13(11):e2303667. doi: 10.1002/adhm.202303667. Epub 2024 Jan 4.
Currently, cisplatin resistance has been recognized as a multistep cascade process for its clinical chemotherapy failure. Hitherto, it remains challenging to develop a feasible and promising strategy to overcome the cascade drug resistance (CDR) issue for achieving fundamentally improved chemotherapeutic efficacy. Herein, a novel self-assembled nanoagent is proposed, which is constructed by Pt(IV) prodrug, cyanine dye (cypate), and gadolinium ion (Gd), for systematically conquering the cisplatin resistance by employing near-infrared (NIR) light activated mild-temperature hyperthermia in tumor targets. The proposed nanoagents exhibit high photostability, GSH/H-responsive dissociation, preferable photothermal conversion, and enhanced cellular uptake performance. In particular, upon 785-nm NIR light irradiation, the generated mild temperature of ≈ 43 °C overtly improves the cell membrane permeability and drug uptake, accelerates the disruption of intracellular redox balance, and apparently enhances the formation of Pt-DNA adducts, thereby effectively overcoming the CDR issue and achieves highly improved therapeutic efficacy for cisplatin-resistant tumor ablation.
目前，由于临床化疗失败，顺铂耐药已被认为是一个多步骤级联过程。迄今为止，开发一种可行且有前景的策略来克服级联药物耐药（CDR）问题，以实现根本改善的化疗疗效仍然具有挑战性。在此，提出了一种新型的自组装纳米制剂，它由 Pt(IV)前药、菁染料（cypate）和钆离子（Gd）构建，用于通过在肿瘤靶标中使用近红外（NIR）光激活温和温度的热疗来系统地克服顺铂耐药性。所提出的纳米制剂表现出高的光稳定性、GSH/H 响应性解离、更好的光热转换和增强的细胞摄取性能。特别是，在 785nm NIR 光照射下，产生的约 43°C 的温和温度明显提高了细胞膜通透性和药物摄取，加速了细胞内氧化还原平衡的破坏，并明显增强了 Pt-DNA 加合物的形成，从而有效克服 CDR 问题，并实现对顺铂耐药肿瘤消融的高度改善的治疗效果。
