Department of General Surgery, Zhujiang Hospital; Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Department of Cardiology, Heart Center, Guangdong Provincial Biomedical Engineering Technology Research, Center for Cardiovascular Disease, Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
ACS Nano. 2024 Oct 15;18(41):28038-28051. doi: 10.1021/acsnano.4c07085. Epub 2024 Oct 3.
The low permeability and heterogeneous distribution of drugs (including nanomedicines) have limited their deep penetration into solid tumors. Herein we report the design of gold nanoparticles with virus-like spikes (AuNVs) to mimic viral shapes and facilitate tumor penetration. Mechanistic studies revealed that AuNVs mainly entered cells through macropinocytosis, then transported to the Golgi/endoplasmic reticulum system via Rab11-regulated pathway, and finally exocytosed through recycling endosomes, leading to high cellular uptake, effective transcytosis, and deep tumor penetration compared to gold nanospheres (AuNPs) and gold nanostars (AuNSs). The high tumor accumulation and deep tumor penetration of mitoxantrone (MTO) facilitated by AuNVs endowed effective chemophotothermal therapy when exposed to a near-infrared II laser, significantly reducing tumor sizes in a mouse model of colorectal cancer. This study reveals a potent mechanism of viral-like structures in tissue penetration and highlights their potential as effective drug delivery carriers.
药物（包括纳米药物）的低渗透性和异质性分布限制了它们在实体瘤中的深层渗透。在此，我们报告了具有类似病毒形状的金纳米粒子（AuNVs）的设计，以促进肿瘤穿透。机制研究表明，AuNVs 主要通过巨胞饮作用进入细胞，然后通过 Rab11 调节途径运输到高尔基体/内质网系统，最后通过再循环内体胞吐，与金纳米球（AuNPs）和金纳米星（AuNSs）相比，导致高细胞摄取、有效转胞和深层肿瘤穿透。米托蒽醌（MTO）在 AuNVs 的促进下在肿瘤中的高积累和深层渗透赋予了近红外 II 激光照射下有效的化学光热治疗，显著减小结直肠癌小鼠模型中的肿瘤大小。本研究揭示了病毒样结构在组织穿透中的强大机制，并强调了它们作为有效药物递送载体的潜力。
