Wu Danjun, Ji Yaning, Ji Weili, Tian Hong, Dai Yiwei, Chen Yifei, Shen Gongmin, Yang Gensheng
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China.
Hangzhou Guoguang Pharmaceutical Co, Ltd, Hangzhou 310018, China.
Biomacromolecules. 2025 Jul 14;26(7):4184-4196. doi: 10.1021/acs.biomac.5c00186. Epub 2025 Jun 6.
Nanomedicines with a size of approximately 200 nm preferentially accumulate at the tumor peripheries but exhibit limited penetration into deeper hypoxic regions. To overcome this, we engineered near-infrared (NIR) light-triggered, size-tunable nanomicelles (Au@PtNRs/DOX-M) to enhance tumor accumulation and penetration, while alleviating hypoxia. Dumbbell-shaped platinum-deposited gold nanorods (Au@PtNRs), with a high photothermal conversion efficiency (68.44%), were integrated into thermoresponsive, doxorubicin (DOX)-loaded nanomicelles. Upon NIR irradiation, Au@PtNRs induced light-to-heat conversion, disassembling micelles into ultrasmall micelles for enhanced tumor penetration and on-demand DOX release. Concurrently, Pt nanoparticles catalyzed the decomposition of reactive oxygen species (ROS) to mitigate ROS-induced damage to adjacent healthy cells, and scavenged the elevated HO within tumors, generating abundant oxygen to reoxygenate the hypoxic microenvironment. This study establishes an efficient, size-tunable nanomicelle platform for enhancing hypoxia-impeded deep penetration of nanomedicines and offers a promising strategy for synergistic chemo-photothermal therapy, achieving tumor inhibition rates of up to 99% in MCF-7 tumor-bearing mice.
尺寸约为200纳米的纳米药物优先在肿瘤周边积聚，但对更深层缺氧区域的渗透有限。为了克服这一问题，我们设计了近红外（NIR）光触发、尺寸可调的纳米胶束（Au@PtNRs/DOX-M），以增强肿瘤积聚和渗透，同时缓解缺氧。将具有高光热转换效率（68.44%）的哑铃形铂沉积金纳米棒（Au@PtNRs）整合到热响应性、负载阿霉素（DOX）的纳米胶束中。在近红外照射下，Au@PtNRs诱导光热转换，将胶束分解为超小胶束，以增强肿瘤渗透和按需释放DOX。同时，铂纳米颗粒催化活性氧（ROS）分解，减轻ROS对相邻健康细胞的损伤，并清除肿瘤内升高的羟基自由基，产生大量氧气使缺氧微环境再氧合。本研究建立了一个高效、尺寸可调的纳米胶束平台，用于增强纳米药物受缺氧阻碍的深层渗透，并为协同化疗-光热疗法提供了一种有前景的策略，在荷MCF-7肿瘤小鼠中实现了高达99%的肿瘤抑制率。
