Integrating biodegradability with nanostructures has generated nanomaterials with minimized long-term toxicity and important biomedical applications. However, it remains challenging to obtain well-defined biodegradable nanomaterials through simple and robust protocols. This research is focused on a methodology for the synthesis of environmentally benign polymeric nanomaterials via thiol-ene miniemulsion-crosslinking reactions. The PI previously found high reactivity of an allyl-functionalized lactide (LA) monomer in thiol-ene reactions. A well-defined PLA-based copolymer with pendent allyl groups was further obtained by organo-catalyzed ring-opening copolymerization of the functional monomer with LA; transparent miniemulsions were prepared with relatively low surfactant concentrations. A critical question is whether thiol-containing miniemulsion systems have sufficient stability to allow well-controlled templating synthesis. In this exploratory investigation, the PI plans to synthesize PLA-based nanoparticles using the thiol-ene reaction between the PLA-based copolymer and multifunctional thiols within miniemulsion nanodroplets. This is a high-risk approach because it has not been previously explored. However, if successful, results could lead to a new avenue for making biodegradable nanaomaterials. Experimentally, monitored by DLS, stability of the miniemulsion reaction systems will be investigated, and miniemulsion conditions will be optimized to exert precise control over the resulting nanoparticles. DLS, FT-IR, AFM, and TEM will be utilized to characterize the nanoparticles.
Broader Impacts
The research could lead to extensive synthetic studies of biodegradable nanoparticles with different structural features, as well as detailed investigations of degradation and delivery behaviors of the nanoparticles. Since these biodegradable nanostructures may be used to deliver anti-cancer drugs through nanoencapsulation or conjugation, eventually this project may have societal health-care benefits. A video on nanoparticle synthesis by thiol-ene miniemulsion crosslinking will be prepared as open source material available on the internet (including YouTube) to promote polymer education. Broad dissemination will also be through the 'Passport STEM' program for middle and high school students from Buffalo and surrounding school districts (both public and private schools).
With minimized long-term toxicity, biodegradable nanomaterials have attracted broad interests because of their significant biomedical applications. It is important to develop simple and robust methods for the preparation of biodegradable nanomaterials with well-controlled structures. The research objective of this project is to test an unexplored hypothesis that well-defined cross-linked biodegradable nanoparticles can be readily synthesized by click miniemulsion cross-linking. With the kind support from NSF, this hypothesis was fully verified, and biodegradable nanoparticles and nanocapsules were obtained by thiol-ene click cross-linking of precursor polymers, i.e. allyl-functionalized polylactide and poly(ethylene glycol)-b-polylactide, using short (30 min) UV irradiation of transparent miniemulsion reaction systems. Well-defined nanostructures of the nanoparticles and nanocapsules were confirmed by instrumental characterizations. Their biodegradability was proven through enzymatic degradation study. Moreover, the synthetic strategy for biodegradable nanomaterial preparation was further expanded by applying azide-alkyne click chemistry for miniemulsion cross-linking. Well-defined paclitaxel-conjugated polylactide-based nanoparticles were quantitatively synthesized by azide-alkyne cross-linking reaction between acetylene-functionalized polylactide and diazide-functionalized paclitaxel in miniemulsion, and their biodegradability was also verified. The research project may bring transformative impacts in the research areas of material synthesis and biomedical delivery. The transparent miniemulsion templates may be used in other types of photo-induced reactions for efficient synthesis of a broad variety of nanomaterials. The biodegradable nanoparticles and nanocapsules may serve as ideal scaffolds for drug delivery. Because paclitaxel is a clinically used anti-cancer drug, the paclitaxel-conjugated biodegradable nanoparticles potentially may be used for chemotherapy. For educational outreach, a video on transparent miniemulsion technique was prepared and posted on YouTube for online broadcasting.
