Targeted pH- and redox-responsive AuS/micelles with low CMC for highly efficient sonodynamic therapy of metastatic breast cancer.

The efficacy of injectable micellar carriers is hindered due to the disassembly of micelles into free surfactants in the body, resulting in their dilution below the critical micelle concentration (CMC). Copolymer micelles were developed to address this issue, containing a superhydrophilic zwitterionic block and a superhydrophobic block with a disulfide bond, which exhibited a CMC lower than conventional micellar carriers. Cleavable copolymers composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) zwitterion and polycaprolactone CHLZW as the shell, with gold nanoparticles as their core, were studied to deliver doxorubicin to tumor cells while reducing the side effect of the free cytotoxic agent. The research focused on the impact of gold nanoparticles present in targeted TMT-micelles core on stability and in vivo bioavailability and sonotoxicity of the nanoparticles, as well as their synergistic effect on targeted chemotherapy. The nanomicelles prepared in this study demonstrated excellent biocompatibility and responsiveness to stimuli. PCL-SS-MPC nanomicelles displayed drug release in response to GSH and pH, resulting in high DOX release at GSH 10 mM and pH 5. Our findings, supported by MTT, flow cytometry, and confocal laser scanning microscopy, demonstrated that AuS-PM-TMTM-DOX micelles effectively induced apoptosis and enhanced cellular uptake in MCF7 and MDA-MB231 cell lines. The cytotoxic effects of AuS-PM-DOX/US on cancer cells were approximately 38 % higher compared to AuS-PM-DOX samples at a concentration of IC50 0.68 nM. This increase in cellular toxicity was primarily attributed to the promotion of apoptosis. The introduction of disulfide linkages in AuSNPs resulted in increased ROS production when exposed to ultrasound stimulation, due to a reduction in GSH levels. Compared to other commercially available nanosensitizers such as titanium dioxide, exposure of AuS-PM to ultrasound radiation (1.0 W/cm, 2 min) significantly enhanced cavitation effects and resulted in 3 to 5 times higher ROS production. Furthermore, laboratory experiments using human breast cancer cells (MDA-MB-231, MCF7) demonstrated that the toxicity of AuS-PM in response to ultrasound waves is dose-dependent. The findings of this study suggest that this formulated nanocarrier holds great potential as a viable treatment option for breast cancer. It can induce apoptosis in cancer cells, reduce tumor size, and display notable therapeutic efficacy.

Recent progress in PLGA-based microneedle-mediated transdermal drug and vaccine delivery.

Microneedles (MNs) have recently been found to have applications in drug, vitamin, protein and vaccine delivery. Polymeric MN arrays continue to attract increasing attention due to their capability to bypass the skin's stratum corneum (SC) barrier with minimal invasiveness. These carriers can achieve the targeted intradermal delivery of drugs and vaccines and improve their transdermal delivery level. As a nontoxic FDA-approved copolymer, polylactic glycolic acid (PLGA) has good biocompatibility and biodegradability. Currently, PLGA-based MNs have a noticeable tendency to be utilized as a delivery system. This study focuses on the most recent advances in PLGA-based MNs. Both PLGA nanoparticle-based MNs and PLGA matrix-based MNs, created for the delivery of vaccines, drugs, proteins and other therapeutic agents, are discussed. The paper also discusses the various types of MNs and their potential applications. Finally, the prospects and challenges of PLGA-based MNs are reviewed.