Smart anti-vascular nanoagent induces positive feedback loop for self-augmented tumor accumulation.

Abstract

How to achieve efficient drug accumulation in the tumor with low vascular density is a great challenge but the key to push the limit of anti-vascular therapeutic efficacy. Herein, we report a charge-reversible nanoparticles of gambogenic acid (CRNP-GNA) that would induce the positive feedback loop between increased tumor vascular permeability and improved drug accumulation. This positive feedback loop would remarkably improve tumor vascular permeability for efficient drug accumulation through few residue vessels. As compared to its charge-irreversible analogue in the latter injections, the accumulation in tumor and vascular permeability and retention indexes (VPRI) in CRNP-GNA group respectively boosted from nearly equal to 8.32 and 60 times, while its tumorous microvessel density decreased from nearly equal to only 7%. The self-augmented accumulation consequently amplified the antitumor efficacy via multiple pathways of anti-angiogenesis, vascular disruption and pro-apoptosis, where 5 out of 6 tumors in animal models were completely cured by CRNP-GNA. This work confirms that the underlying positive feedback loop for anti-vascular therapy could be induced by charge-reversible drug delivery nanosystem to achieve efficient and self-augmented drug accumulation even in the tumor with few vessels. It provides a novel strategy to conquer the dilemma between anti-vascular efficacy and drug accumulation.

• Authors: Mengting Du, Tingting Geng, Rongrong Yu, Gang Song, Hui Cheng, Yu Cao, Weidong He, Abdul Haleem, Qinglin Li, Rongfeng Hu, Shengqi Chen
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 356 Pg. 595-609 (04 2023) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 36924896 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023. Published by Elsevier B.V.

Topics

• Animals
• Feedback
• Neoplasms (drug therapy)
• Drug Delivery Systems
• Nanoparticles (chemistry)
• Cell Line, Tumor