Targeting and microenvironment-improving of phenylboronic acid-decorated soy protein nanoparticles with different sizes to tumor

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.

Phenylboronic acid modification augments the lysosome escape and antitumor efficacy of a cylindrical polymer brush-based prodrug

“…22 the mean fluorescence intensities in the CT26, MCF-7 and HepG2 cells incubated with BCPB-B-DOX are 1.67-fold, 2.67-fold, and 2.58-fold the intensities in the corresponding cells treated with BCPB-DOX, respectively, which can be attributed to the targeting effect of the PBA group. The effect degree of the PBA group on the cellular uptake is positively related with the SA expression level of the cells, hence the cellular uptake results are consistent well with the fact that MCF-7 cells have the highest SA level among the three cell lines 37,45 . The higher cellular uptake of BCPB-B-DOX than BCPB-DOX also explains its lower IC50 in the three cell lines.…”

Self-Assembly of Crystalline Vesicles from Nonplanar π-Conjugated Nanocycles

“…After stabilization in the second stage, final dye release reached approximately 80% of initial dye concentration, while some solid spheres released <50% of dyes in similar experiments. 42 Compared with some solid spheres, CPP vesicles released more dye, which indicated that the wall of CPP vesicles might not be very thick or dense.…”

Targeting the “Sweet Side” of Tumor with Glycan-Binding Molecules Conjugated-Nanoparticles: Implications in Cancer Therapy and Diagnosis

“…There is great potential for the use of boronic aid and derivates application for the development of targeted nanoparticles towards cancer cells for drug delivery, cell imaging, and therapy. Soy protein NPs bearing phenylboronic acid (PBA) on their outer surface were used to improve the tumor microenvironment (TME) targeting and penetration of NPs inside the tumor [ 92 ]. It was also observed that the incorporation of the phenylboronic acid group into chitosan NPs imparted a surface charge-reversible characteristic to the NPs, increasing the internalization of NPs into 2D and 3D cell models [ 93 ].…”