Engineering Polyzwitterion and Polydopamine Decorated Doxorubicin-Loaded Mesoporous Silica Nanoparticles as a pH-Sensitive Drug Delivery.

Feng Ji,Zhihui Qin,Jing Cui,Ershuai Zhang,Jinmei Wang,Fanglian Yao,Hong Sun,Shuofeng Li

doi:10.3390/polym10030326

Abstract

Multifunctional drug carriers have great applications in biomedical field. In this study, we introduced both polydopamine (PDA) and zwitterionic polymer of poly(3-(3-methacrylamidopropyl-(dimethyl)-ammonio)propane-1-sulfonate) (PSPP) onto the surface of mesoporous silica nanoparticles (MSNs) to develop a novel nanoparticle (MSNs@PDA-PSPP), which was employed as a new kind of drug carrier for the delivery of doxorubicin (DOX). The PDA coating, as a gatekeeper, could endow the drug carrier with pH-sensitive drug release performance. The outermost PSPP layer would make the drug carrier possess protein resistance performance. The chemical structure and properties were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS) and thermogravimetric analysis (TGA). MSNs@PDA-PSPP could keep good colloidal stability within 72 h in phosphate buffered saline (PBS) and protein solutions. Meanwhile, MSNs@PDA-PSPP exhibited a high drug loading for DOX. In vitro drug release experiments suggested MSNs-DOX@PDA-PSPP exhibited pH-dependent drug release behaviors. Besides, MSNs@PDA-PSPP had no cytotoxicity to human hepatocellular carcinoma cells (HepG2 cells) even at a concentration of 125 µg/mL. More importantly, cellular uptake and in vitro anticancer activity tests suggested that MSNs-DOX@PDA-PSPP could be taken up by HepG2 cells and DOX could be successfully released and delivered into the cell nuclei. Taken together, MSNs@PDA-PSPP have great potential in the biomedical field.

Highlights

Over the past decades, mesoporous silica nanoparticles (MSNs) have drawn great interest due to their unique properties such as high biocompatibility, easy synthesis and functionalization [1,2,3,4,5,6].MSNs possess a high loading capacity for small drugs, proteins and genes or co-delivery drugs, which is ascribed to their high surface area and large pore volume [7,8]
PSPP was synthesized by reversible addition-fragmentation-chain-transfer (RAFT) polymerization as it could precisely control the length of the desired polymer
The reaction was carried out in 0.5 M NaCl solution because it was well known that electrolyte could enhance the water solubility of PSPP

Summary

Introduction

MSNs possess a high loading capacity for small drugs, proteins and genes or co-delivery drugs, which is ascribed to their high surface area and large pore volume [7,8]. Considering the open pore structure of MSNs, the inherent premature leakage or uncontrolled release of the loaded drugs from MSNs. Polymers 2018, 10, 326; doi:10.3390/polym10030326 www.mdpi.com/journal/polymers. In order to reduce the premature leakage or uncontrolled release, capping the open pore by physical or chemical method to construct a gate-structure (named gatekeepers) is needed [9]. Various gatekeepers have been successfully prepared, such as macromolecule capping, polymer coating and nanomachine construction [10,11,12]

Objectives

Methods

Results

Conclusion