Multifunctional microbubbles comprising poly(lactic-co-glycolic acid), chitosan, polyethylene glycol, and folic acid for targeted cancer therapy

The advancement of targeted drug delivery systems has been pivotal in improving the therapeutic efficacy of anticancer drugs while reducing systemic toxicity. This study presents the synthesis, characterization, and evaluation of a novel polymeric microbubble (MB) with a meticulously designed shell composed of poly (lacticco-glycolic acid), chitosan, polyethylene glycol, and folic acid loaded with gold nanoparticles via encapsulating a perfluorohexane core. The polymeric MB was synthesized using a modified emulsion method, designed to provide stability, biocompatibility, controlled drug release, and targeted delivery. The MB's properties, including size, zeta potential, and morphology, were characterized using transmission electron microscopy, dynamic light scattering, and optical microscopy. Effective methotrexate encapsulation and controlled release were evaluated using UV-vis spectroscopy, demonstrating the polymeric shell's effectiveness. The MB's biocompatibility and cellular uptake were confirmed through cytotoxicity and in vitro studies. The influence of emulsion parameters in nanodroplets preparation was investigated, revealed their critical role in optimizing particle size distribution. This newly developed copolymer not only exhibited enhanced stability but also demonstrated excellent ultrasound and temperature responsiveness, highlighting its potential as a theranostic agent for both cancer imaging and therapy.