Abstract

It is essential for nanoparticles to delivery drugs accurately and penetrate deeply to tumor. However, complicated tumor microenvironment such as elevated tumor interstitial fluid pressure (IFP) and solid stress reduces the transport efficiency of nanomedicines in tumor.Methods: We herein report a drug delivery system of phenylboronic acid-decorated soy protein nanoparticles with the size of 30 nm, 50 nm and 150 nm. In vitro examinations including cytotoxicity, cellular uptake and penetration in multicellular tumor spheroids and in vivo observations including IFP and tumor solid stress measurements and antitumor activity were performed.Results: It was found that phenylboronic acid moiety could endow the nanoparticles actively targeting affinity to sialic acid (SA) which overexpressed in tumor cells. Simultaneously soy protein could improve tumor microenvironment such as reduction of IFP and tumor stress. Among the soy protein nanoparticles with different sizes, 30 nm-sized nanoparticles showed the best cellular uptake and highest cytotoxicity in vitro after loading doxorubicin (DOX). In vivo, 30 nm-sized nanoparticles showed the best tumor microenvironment improvement efficiency, leading to the enhanced drug accumulation and antitumor efficiency when combination with DOX.Conclusion: Our study introduces a bioactive nanoparticulate design strategy to actively target and significantly improve tumor microenvironment for enhanced cancer therapy.

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