Schiff-Linked PEGylated Doxorubicin Prodrug Forming pH-Responsive Nanoparticles With High Drug Loading and Effective Anticancer Therapy

Abstract

Developing efficacious drug delivery systems for targeted cancer chemotherapy remains a major challenge. Here we demonstrated a kind of pH-responsive PEGylated doxorubicin (DOX) prodrug via the effective esterification and Schiff base reactions, which could self-assemble into the biodegradable micelles in aqueous solutions. Owing to low pH values inside the tumor cells, these PEG-Schiff-DOX nanoparticles exhibited high drug loading ability and pH-responsive drug release behavior within the tumor cells or tissues upon changes in physical and chemical environments, but they displayed good stability at physiological conditions for a long period. CCK-8 assay showed that these PEGylated DOX prodrugs had a similar cytotoxicity to the MCF-7 tumor cells as the free DOX drug. Moreover, this kind of nanoparticle could also encapsulate small DOX drugs with high drug loading, sufficient drug release and enhanced therapeutic effects toward MCF-7 cells, which will be benefited for developing more drug carriers with desirable functions for clinical anticancer therapy.

A Review on the Antimicrobial Activity of Schiff Bases: Data Collection and Recent Studies

“…In addition, experimental evidence regarding nanoparticles with Schiff bases for the diagnosis and treatment of tumors have been also reported. Some prodrug nanomedicines deriving from Schiff bases with doxorubicin and polyethylene glycol (PEG), one of the most widely used hydrophilic polymer approved by Food and Drug Administration (FDA) with negligible toxicity, have been described for their antitumor activity [ 84 ]. Moreover, the functionalization of chitosan nanoparticles with the anticancer 5-fluorouracil to obtain chitosan nanocarriers through Schiff base formation has been studied [ 85 ].…”

The Role of Tumor Inflammatory Microenvironment in Lung Cancer

“…It mainly includes tumor cells, tumor-associated fibroblasts, immune cells, vascular endothelial cells, extracellular matrix (ECM) and its degrading enzymes, various growth factors, and inflammatory factors. Moreover, it has special physical and chemical characteristics (e.g., hypoxia, low pH) (Wang et al, 2016;Wang et al, 2019;Jiang et al, 2020;Zheng et al, 2020;Liu et al, 2021;Song et al, 2021;Zheng et al, 2021). The TME has multiple effects on tumor initiation, development, and progression, and the mechanism is complex.…”

Preparation of Spherical Cellulose Nanoparticles from Recycled Waste Cotton for Anticancer Drug Delivery

“…The passive diffusion of free DOX molecules were much quicker than the internalization processes of polymeric nanoparticles. [44] Gou et al prepared a self-assembling prodrug forming nanoparticles for DOX delivery. Polyethylene glycol (PEG) was conjugated to DOX to form the amphiphilic prodrug PEG-DOX.…”