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Issue 11, 2020
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Enhanced nanoparticle accumulation by tumor-acidity-activatable release of sildenafil to induce vasodilation

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Abstract

Inefficient nanoparticle accumulation in solid tumors hinders the clinical translation of cancer nanomedicines. Herein, we proposed that sildenafil, a vasodilator ampholyte, could be used to promote nanoparticle accumulation by inducing vasodilation after its tumor acidity-triggered release from the nanocarriers. To confirm this, sildenafil was first encapsulated in a cisplatin-incorporated polymeric micelle. The dense PEG shell of the micelle reduced its endocytosis by cancer cells, which in return resulted in accumulative extracellular release of protonated sildenafil in the acidic tumor microenvironment. The released sildenafil was found to be more effective in enlarging the tumor blood vessels than could be achieved without sildenafil. As a result, we demonstrated considerable improvement in the intratumoral accumulation of the sildenafil-cisplatin co-loaded nanoparticle and its enhanced cancer therapeutic efficacy over the control group. Given the generality of a dense PEG shell and a hydrophobic part in most clinically developed nanomedicines, this work implies the great potential of sildenafil as a simple and universal adjuvant to selectively promote the intratumoral accumulation of nanomedicines, thus improving their clinical translation.

Graphical abstract: Enhanced nanoparticle accumulation by tumor-acidity-activatable release of sildenafil to induce vasodilation

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Supplementary files

Article information


Submitted
22 Mar 2020
Accepted
14 Apr 2020
First published
15 Apr 2020

Biomater. Sci., 2020,8, 3052-3062
Article type
Paper

Enhanced nanoparticle accumulation by tumor-acidity-activatable release of sildenafil to induce vasodilation

P. Zhang, Y. Zhang, X. Ding, C. Xiao and X. Chen, Biomater. Sci., 2020, 8, 3052
DOI: 10.1039/D0BM00466A

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