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Macroporous organosilicon nanocomposites co-deliver Bcl2-converting peptide and chemotherapeutic agent for synergistic treatment against multidrug resistant cancer.

Abstract：

:Therapeutic biomacromolecules are confronted with in vivo challenges of low bio-stability and poor tumor tissue-penetration. Herein, we report for the first time, our development and characterization of a hybrid nanocomposite for delivering a Bcl-2-converting peptide (NuBCP9, N9 hereafter) and testing its efficacy alone or together with doxorubicin (DOX). The hybrid nanocomposite is composed of the internal large pore sized-mesoporous silica nanoparticles (MSNs) and the external highly-branched polyamidoamine (PAMAM) dendrimers, into which N9 peptide and DOX were encapsulated for the different sub-cellular delivery to treat drug-resistant cancer. The nanocomposite possessed the particle and pore sizes of ~37 nm and ~8 nm, which displayed the superior tumor penetration capacity over naked MSNs both in cultured-3D tumor sphere and in live animal models. Moreover, the dual drug nanocomposite exhibited a great synergistic anticancer effect on Bcl-2-positive cancer cells in vitro and animals with the negligible toxic side effects. The tumor inhibition rate of the nanocomposite (89%) was five times as much as the two drugs combination. This design provides a new effective, safe and versatile strategy to fabricate large pore-sized MSNs with the organic-inorganic hybrid framework to concurrently transport therapeutic peptides and chemotherapeutics to the specific sub-cellular locations for the synergistic cancer therapy and drug resistance reversal, which has significant impact on the development of improved cancer therapeutics.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Xie J,Xu W,Wu Y,Niu B,Zhang X

doi

10.1016/j.canlet.2019.10.018

subject

Has Abstract

pub_date

2020-01-28 00:00:00

pages

340-354

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(19)30515-4

journal_volume

469

pub_type

杂志文章

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