Preparation and evaluation of tumour microenvironment response multistage nanoparticles for epirubicin delivery and deep tumour penetration

Artificial Cells, Nanomedicine, and Biotechnology
Jialing DaiYong Sun

Abstract

Poor tumour penetration became a major challenge for the use of nanoparticles in anticancer therapy. To further enhance the tumour penetration efficiency, we developed a tumour-microenvironment-responsive multistage drug delivery system which was formed layer by layer via electrostatic interaction with cationic drug-loaded nanoparticles, hyaluronidase (HAase) and iRGD-modified gelatin (G-iRGD). The drug-loaded nanoparticles were formed by self-assembling mPEG-PDPA-PG and encapsulation with epirubicin (EPI). Due to the protonation of tertiary amine groups of PDPA segment in acid environment, mPEG-PDPA-PG could enhance the lysosomal escape and the intracellular release of EPI. This NPs/HAase/G-iRGD delivery system showed great biocompatibility in vitro, confirmed by MTT method. In vitro spherical tumour model penetration and in vivo tumour permeability investigation showed HAase coated NPs-EPI (NPs-EPI/HAase) could significantly enhance its penetrating efficiency. The NPs-EPI/HAase could assist in breaking down the hyaluronic acid (HA), which was a key component of extracellular matrix and thereby improving mass transport within the solid tumours. The flow cytometry studies showed that G-iRGD coated NPs-EPI (NPs-EPI/G-iRGD) was m...Continue Reading

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Citations

Feb 11, 2020·Artificial Cells, Nanomedicine, and Biotechnology·Yan LiangYong Sun
Jun 28, 2019·ACS Applied Materials & Interfaces·Jie CaoYong Sun
Jan 12, 2022·Drug Delivery and Translational Research·Zeinabosadat Davoodi, Fatemeh Shafiee

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