Morphology-Mediated\nTumor Deep Penetration for Enhanced\nNear Infrared II Photothermal and Chemotherapy of Colorectal Cancer

The low permeability and heterogeneous distribution of\ndrugs (including\nnanomedicines) have limited their deep penetration into solid tumors.\nHerein we report the design of gold nanoparticles with virus-like\nspikes (AuNVs) to mimic viral shapes and facilitate tumor penetration.\nMechanistic studies revealed that AuNVs mainly entered cells through\nmacropinocytosis, then transported to the Golgi/endoplasmic reticulum\nsystem via Rab11-regulated pathway, and finally exocytosed through\nrecycling endosomes, leading to high cellular uptake, effective transcytosis,\nand deep tumor penetration compared to gold nanospheres (AuNPs) and\ngold nanostars (AuNSs). The high tumor accumulation and deep tumor\npenetration of mitoxantrone (MTO) facilitated by AuNVs endowed effective\nchemophotothermal therapy when exposed to a near-infrared II laser,\nsignificantly reducing tumor sizes in a mouse model of colorectal\ncancer. This study reveals a potent mechanism of viral-like structures\nin tissue penetration and highlights their potential as effective\ndrug delivery carriers.