Synthesis and characterization of redox and ultrasonic dual-responsive organic-inorganic amphiphilic hybrid copolymers for drug delivery

Redox and ultrasonic responsive copolymers MPEG-S-S-P(αN₃CL-g-ibu₇POSS)_x-r-PCL_y bearing grafted hydrophobic polyhedral oligomeric silsesquioxane (POSS) were synthesized through a click reaction between MPEG-S-S-P(αN₃CL)_x-r-PCL_y and alkynyl POSS. The morphology revealed that the copolymers underwent micellization or dissociation transitions in response to the reducing agent and ultrasound treatment. The release rate could be substantially increased and adjusted remotely under ultrasound radiation in the presence of dithiothreitol. The nanoparticles exhibited slight toxicity against HeLa cells. After high-intensity focused ultrasound (HIFU) irradiation, DOX-loaded micelles effectively inhibited the proliferation of HeLa cells with a half-maximal inhibitory concentration of 1.1 μg mL⁻¹, and enhanced cellular uptake.