| dc.description.abstract | Nanomedicine holds great potential for effective treatment against life-threatening diseases by providing efficient transport and controlled release of significant quantities of therapeutic agents to the target sites of the diseased tissue. Despite promising laboratory results, many nanomedicine formulations failed in clinical trials, in part due to heterogeneity in diseased individuals. Individual heterogeneity leads to heterogeneous outcome of nanomedicine treatments, and thus presents a great challenge for clinical translation of nanomedicine. Personalized nanocarriers, with tailored physicochemical properties for a specific individual’s genetic and disease profile, can overcome such a challenge. Therefore, the future of nanomedicine will depend on customization and personalization, and the development of next-generation nanomedicine requires more precise control of the physicochemical characteristics of nanomaterials. Consequently, effective approaches that reduce burdens for controlling physicochemical characteristic of nanomaterials would facilitate bench-to-bedside translation of nanomedicine.
First, we reported co-assembly of two degradable glucose-based amphiphilic block polymers is demonstrated to control nanoparticle size, surface charge, and stimuli-responsive properties, allowing optimization of these constructs for cytosolic drug delivery applications. The accessible procedures presented here for engineering highly tunable nanoparticles from glucose-based, functional, degradable polymers offer versatile strategies for accelerating the development and clinical implementation of such stimuli-responsive, tailored nanocarriers.
Second, we reported a facile fabrication of cell membrane-camouflaged nanocarriers (CMNs) that exhibit tunable paclitaxel (PTX) release kinetics via altering macromolecular stereostructure. Biomimetic-cell-membrane-camouflaged polymeric nanocarriers, possessing advantages related to the functional diversity of natural cell membranes and the physicochemical tailorability of synthetic polymers, serve as promising candidates for a therapeutic platform. This work represents fundamental advances toward a potential personalized nanocarrier technology that would be capable of employing an individual’s RBCs for membrane isolation, together with tuning of cargo loading and release simply via alteration of the biocompatible PLA stereoisomer feed ratio.
Third, we investigated the role that reversible covalent loading of a hydrophobic drug exerts on intra-nanoparticle physical properties and explore the utility of this payload control strategy for tuning the access of active agents and, thereby, the stimuli sensitivity of smart nanomaterials. Interactions between drug molecules, nanocarrier components, and surrounding media influence the properties and therapeutic efficacies of nanomedicines. In this study, glutathione sensitivity was controlled via altering the degree of hydrophobic payload loading of disulfide-linked camptothecin-conjugated sugar-based nanomaterials. This work represents an advancement in drug carrier design by demonstrating the importance of controlling the amount of drug loading on the overall payload and its availability. | |
