Poly(Photosensitizer-Prodrug) Unimolecular Micelles for Chemo-Photodynamic Synergistic Therapy of Antitumor and Antibacteria.

It is crucial to use simple methods to prepare stable polymeric micelles with multiple functions for cancer treatment. Herein, via a "bottom-up" strategy, we reported the fabrication of ß-CD-(PEOSMA-PCPTMA-PPEGMA)21 (ßPECP) unimolecular micelles that could simultaneously treat tumors and bacteria with chemotherapy and photodynamic therapy (PDT). The unimolecular micelles consisted of a 21-arm ß-cyclodextrin (ß-CD) core as a macromolecular initiator, photosensitizer eosin Y (EOS-Y) monomer EOSMA, anticancer drug camptothecin (CPT) monomer, and a hydrophilic shell PEGMA. Camptothecin monomer (CPTMA) could achieve controlled release of the CPT due to the presence of responsively broken disulfide bonds. PEGMA enhanced the biocompatibility of micelles as a hydrophilic shell. Two ßPECP with different lengths were synthesized by modulating reaction conditions and the proportion of monomers, which both were self-assembled to unimolecular micelles in water. ßPECP unimolecular micelles with higher EOS-Y/CPT content exhibited more excellent 1O2 production, in vitro drug release efficiency, higher cytotoxicity, and superior antibacterial activity. Also, we carried out simulations of the self-assembly and CPT release process of micelles, which agreed with the experiments. This nanosystem, which combines antimicrobial and antitumor functions, provides new ideas for bacteria-mediated tumor clinical chemoresistance.

Adhesive polydopamine-based photothermal hybrid hydrogel for on-demand lidocaine delivery, effective anti-bacteria, and prolonged local long-lasting analgesia.

Considering the astonishing prevalence of localized pain affecting billions of patients worldwide, the development of advanced analgesic formulations or delivery systems to achieve clinical applicability is of great significance. In this study, an integrated PDA-based LiH@PDA@Ag@PAA@Gelatin system was designed for sustained delivery of lidocaine hydrochloride (LiH). By optimizing the preparation process and formulation of the hydrogel, the hydrogel exhibited superior mechanical properties, reversibility, adhesion strength, and self-healing attributes. Moreover, PDA@Ag nanoparticles were evenly dispersed within the hydrogel, and the optimized PDA@Ag@PAA@Gelatin showed a higher photothermal conversion efficiency than that of pure PDA. Importantly, LiH@PDA@Ag@PAA@Gelatin could effectively capture and eradicate bacteria through the synergistic interaction between near-infrared (NIR), PDA, Ag and LiH. In vitro and in vivo tests demonstrated that LiH@PDA@Ag@PAA@Gelatin exhibited higher drug delivery efficiency compared to commercial lidocaine patches. By evaluating the mechanical pain withdrawal threshold of the spared nerve injury (SNI) model in rats, it was proven that LiH@PDA@Ag@PAA@Gelatin enhanced and prolonged the analgesic effect of LiH. Furthermore, LiH@PDA@Ag@PAA@Gelatin induced by NIR possessed excellent on-demand photothermal analgesic ability. Therefore, this study develops a convenient method for preparing localized analgesic hydrogel patches, providing an important step towards advancing PDA-based on-demand pain relief applications.

Mesoscopic Simulations of Diselenide-Containing Crosslinked Doxorubicin-Loaded Micelles and Their Tumor Microenvironment Responsive Release Behaviors.

There is currently limited research on the structure-property relationship of reduction stimuli-responsive polymeric crosslinked micelles using mesoscopic simulations. Herein, dissipative particle dynamics (DPD) simulations were used to simulate the self-assembly process of the blank non-crosslinked micelle, the structure and doxorubicin (DOX) distribution of diselenide crosslinked micelle with different crosslinker contents (CCs) based on the nearest-neighbor bonding principle. The results revealed that the formation of a three-layer spherical micelle and the loaded DOX mainly distributed in the polycaprolactone (PCL) core and hydroxyethyl methacrylate (HEMA) mesosphere. The larger the dosage of DOX, the more DOX encapsulated, but the encapsulation of DOX in the hydrophobic domain would reach saturation when the dosage increased to 6.0 %. In micelles with lower CCs or crosslinking levels (CLs), DOX entered the middle layer and the inner core faster. Then, based on the nearest media-bead bond breaking principle and subsequently DPD simulation, the effects of different CCs on the micelle structure and DOX release properties were investigated. Low CC could cause fast drug release. With the increase of CCs, the micelle showed a slower DOX release trend. The multilayer crosslinked network system also affected the DOX release rate. Hence, this work can provide some mesoscale guidance for the structural design and structure-property relationship of stimuli-responsive reversible crosslinked micelles for drug delivery.