Drug loaded hydrogel nanoparticles with long retention in tumor and multi drug co delivery for melanoma treatment

Abstract

This study aims to address the issue of immune clearance and inaccurate targeting of drug-loaded nanoparticles during intravenous injection, which may lead to partial drug release into non target tissues or organs, damage to normal tissues and low drug utilization. Herein, multi-drug co-delivery nanoparticles with intratumoral long retention capability were developed for melanoma treatment. This study adopted a dual drug loading strategy of curcumin and dexamethasone and designed a drug-loaded nano-system based on polyglutamic acid and caffeic acid. The results indicate that the introduction of caffeic acid endowed nanoparticles with the property of long-term retention in melanoma sites, while also obtaining a certain inhibitory effect on melanoma growth and good antioxidant properties. To make nanoparticles more stable in water environment, we employed esterification reaction to introduce ester bond to enhance the water resistance of nanoparticles, thus giving them stability in water environment. Two drugs with different hydrophilicity were co-loaded into nanoparticles through grafting and π-π stacking. The experimental results in vitro and in vivo indicate that such strategy and design have achieved long-term retention of nanoparticles at tumor site, and meanwhile allow nanoparticles to effectively inhibit the growth and metastasis of tumor cells, achieving ideal therapeutic effects on melanoma treatment.