Poly(oligo(ethylene glycol) methyl ether methacrylate) Capped pH-Responsive Poly(2-(diethylamino)ethyl methacrylate) Brushes Grafted on Mesoporous Silica Nanoparticles as Nanocarrier.

Khalid M Alotaibi,Abdullah M Alswieleh,Latifah H Alfhaid,Ahmed M El-Toni,Maqusood Ahamed,Abdurrahman A Almethen,Abeer M Beagan

doi:10.3390/polym13050823

Abstract

In this paper, a new pH-responsive nanosystem based on mesoporous silica nanoparticles (MSNs) was developed for cancer therapy. Poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA) was grafted on their outer surface and acts as a gatekeeper, followed by subsequent modification of the polymer by cysteine (MSN-PDEAEMA-Cys) and poly(oligo(ethylene glycol) methyl ether methacrylate) (MSN-PDEAEMA-Cys-POEGMEMA). The physicochemical properties of these nanocarriers were characterized using scanning and transmission electron microscopies (SEM and TEM), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and dynamic light scattering (DLS). The synthesized nanoparticles were well-dispersed with a diameter of ca. 200 nm. The obtained XPS results confirm the successful modification of MSN-PDEAEMA with Cys and POEGMEMA by increasing the peak intensity of C–O and C=O groups at 286.5 and 288.5 eV, respectively. An anti-cancer drug, doxorubicin (DOX), was encapsulated into the fabricated nanoplatform. The DOX release amount at physiological pH of 7.4 was limited (10%), while an accumulation drug release of ca. 35% was accomplished after 30 h in acidic media. The MTT cell line was used to assess the cytotoxicity of the unloaded and DOX-loaded fabricated nanoplatforms. Upon loading of DOX on these nanomaterials, they showed significant toxicity to human liver cancer cells. These results suggest that the prepared nano-structured materials showed good biocompatibility as well, and they can serve as nanocarriers for the delivery of anti-cancer drugs.

Highlights

As illustrated in Scheme 1, hybrid mesoporous silica nanoparticles were synthesized in multiple steps
Poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA) brushes were grown on the outer surface of mesoporous silica nanoparticles (MSNs) via SI-ARGET-ATRP
POEGMEMA was used to cap the surface via the thiol-Michael addition click reaction in the presence of TEA

Summary

Introduction

Cancer is considered to be the second leading cause of death worldwide, accounting for an estimation of over 10 million deaths in 2020 [1]. Cancer can proliferate indefinitely and migrate to normal tissues. The excessive metabolite accumulation of the biological microenvironment in cancerous tissues is different from normal tissues, leading to acidic and hypoxic features [2,3]. Multi-sensitive drug delivery systems (DDSs) have been designed and developed to selectively release drug molecules in the microenvironment of diseased tissues and significantly enhance anti-cancer activity [4,5,6]. The ideal drug delivery system should have the ability to release the therapeutic agent in the right dose and at the right site within an acceptable period of time [10]

Methods

Results

Conclusion