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.
Highlights
Biodegradable nanoparticles have been intensively utilized as promising candidates for targeted cancer therapy over a long period, because they possess the increased drug solubility, prolonged circulation time, improved pharmacokinetic properties, good bioavailability, enhanced tumor accumulation at the tumor sites, high therapeutic effects and low systemic side effects (1–8)
Sui et al reported that DOX was conjugated into the Polyethylene glycol (PEG) via an acid-cleavable hydrazone bond, but this doxorubicin prodrug system displayed the insensitive pH response, which exhibited a small DOX release with only 12% drug content within 72 h at pH 5.0
The signals at d 8.0–8.3 ppm were attributed to the benzene components and the resonance peak of d 10.2 ppm belonged to the proton of aldehyde group
Summary
Biodegradable nanoparticles have been intensively utilized as promising candidates for targeted cancer therapy over a long period, because they possess the increased drug solubility, prolonged circulation time, improved pharmacokinetic properties, good bioavailability, enhanced tumor accumulation at the tumor sites, high therapeutic effects and low systemic side effects (1–8). Among these various nanomedicines such as nanoparticles, polymeric micelles, vesicles, nanogels, liposomes and polymer conjugates, prodrug-based nanoparticles have drawn much more attention due to their simple structure, feasible preparation and great potential in clinical translation (9–11). Wen et al had prepared a highdensity DOX component via covalent decoration on the nanocarrier, which could be effectively released in the acidic tumor tissue and significantly improved chemotherapy efficacy (19)
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