Transcytosis-enabled active extravasation of tumor nanomedicine

• Published in: Advanced drug delivery reviews 2022-10, Vol.189, p.114480-114480, Article 114480
• Main Authors: Zhou, Quan, Li, Junjun, Xiang, Jiajia, Shao, Shiqun, Zhou, Zhuxian, Tang, Jianbin, Shen, Youqing
• Format: Article
• Language: English
• Subjects: Active extravasation; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Drug Delivery Systems; Endothelial Cells; Humans; Nanomedicine; Neoplasms - drug therapy; Neoplasms - pathology; Transcytosis; Tumor nanomedicine
• ISSN: 0169-409X; 1872-8294
• DOI: 10.1016/j.addr.2022.114480

Nanomedicines can extravasate from tumor vascular lumen into solid tumors via the EPR effect (a) or transcytosis (b). Transcytosis can be further subcategorized as intracellular vesicles-mediated (1), vesivulo-vacuolar organelles (VVOs)-mediated (2) or fenestrae-mediated (3) pathways. [Display omitted] Extravasation is the first step for nanomedicines in circulation to reach targeted solid tumors. Traditional nanomedicines have been designed to extravasate into tumor interstitium through the interendothelial gaps previously assumed rich in tumor blood vessels, i.e., the enhanced permeability and retention (EPR) effect. While the EPR effect has been validated in animal xenograft tumor models, accumulating evidence implies that the EPR effect is very limited and highly heterogeneous in human tumors, leading to highly unpredictable and inefficient extravasation and thus limited therapeutic efficacy of nanomedicines, including those approved in clinics. Enabling EPR-independent extravasation is the key to develop new generation of nanomedicine with enhanced efficacy. Transcytosis of tumor endothelial cells can confer nanomedicines to actively extravasate into solid tumors without relying on the EPR effect. Here, we review and prospectthe development of transcytosis-inducing nanomedicines, in hope of providing instructive insights for design of nanomedicines that can undergo selective transcellular transport across tumor endothelial cells, and thus inspiring the development of next-generation nanomedicines for clinical translation.