Galactose-functionalized injectable thermosensitive microgels for target specific uptake in hepatoma cells

Abstract

Microgels acts as a potential candidate for responsive composite materials, which has been favored by scientists because of its excellent colloid stability, easy integration, and most of their surface area can be used as support after modification. Specififically, microgels are fascinating capable of maintaining good biocompatibility and controlled-release in vivo and making the possible for applications in biomaterials and biomedicines. Besides, in the process of microgel synthesis, some targeting factors can be combined to achieve the purpose of cell targeting and uptake. Therefore, how to fundamentally design microgels is an urgent problem to be solved. In this study, we design and synthesize an injectable microgel P(DEGMA-co-OVNGal) that is made of 2-methyl-2-acrylate-2-(2-methoxy ethoxy) ethyl ester (DEGMA) and glycopolymer (OVNGal) that is thermoresponsive and contains galactose. When the content of crosslinking agent is regulated, the microgel will realize the transformation from sol to gel at the temperature around human body, causing the controlled release of the loaded drugs. With the increase of crosslinker content from 1% to 7%, the appearance of microgel changed from loose and ordered to compact and hard morphology, the swelling ratio of microgel decreased from 187% to 142%, and the phase volume transition temperature decreased from 29.2°C to 28°C. The results indicated that when the monomer ratio (DEGMA: OVNGal) increased from 2:1 to 40:1 with the amount of crosslinking agent at 1%, the particle size of microgel increased from 460 nm to 660 nm. In vitro released studies confirmed that the cumulative released DOX (doxorubicin, as a selected model drug) from the microgel can reach 50% after 7 days. Furthermore, in vitro experiments demonstrated that the injectable microgel P(DEGMA-co-OVNGal) can target HepG2 cells effectively and meantime dispalys excellent biocompatibility. Therefore, the injected microgels based on P(DEGMA-co-OVNGal) have the potential to serve as a robust and promising drug delivery carrier for targeted cancer therapy.

Graphical Abstract