Nanomaterials with radiation responsiveness

Radiotherapy is one of the most used therapy for cancer patients. More than 60% of cancer patients receive radiotherapy as part of their treatment. To overcome the side-effects of chemotherapy and radiotherapy, we propose to use nanomaterials that respond to radiation to combine the two mainstream treatment modalities together. We developed a gamma-ray-responsive hydrogel based on a diselenide-containing polymer and a peptide amphiphile. Gamma-ray irradiation triggers a gel-to-sol transition, providing a powerful platform to combine chemotherapy with radiotherapy. To further enhance the sensitivity of radiation response, we hypothesized that incorporating tellurium would improve their reactivity. Indeed, tellurium-containing polymer micelles successfully boost the sensitivity of the gamma-ray response to as low as 2 Gy, a daily dosage for clinical radiotherapy. This combined therapy strategy could achieve better control on both the systematic and local levels, therefore improving human health.

Keywords: Molecular Design, Biomaterials, Nanomaterial, Radiotherapy

Angew. Chem. Int. Ed. 2013, 52, 6233; J. Am. Chem. Soc. 2014, 136, 5132

Radioprotectors for biological systems

Ionizing radiation is a double-edged sword. To protect human tissues against harmful ionizing radiation, we designed nature-inspired selenium-containing melanin. Melanins are a ubiquitous family of heterogenous biopolymers that act as photo or radiation protection agents in biology. Inspired by nature’s sulfur-containing pheomelanin, which has been shown to better attenuate X-rays compared to eumelanin, we hypothesized that if a selenium-enriched melanin existed, it would be an even better protector against X-rays than pheomelanin. We introduce a novel selenium analogue of pheomelanin through chemical and biosynthetic routes. The resulting selenomelanin effectively prevented neonatal human epidermal keratinocytes from G2/M phase arrest under high-dose X-ray irradiation. Bridging selenium chemistry with polymer synthesis can create new biomaterials for protection during clinical radiotherapy and space exploration.

Keywords: Ionizing Radiation, Radioprotector, Materials for Space Exploration

J. Am. Chem. Soc. 2020, 142, 12802; J. Am. Chem. Soc. 2021, 143, 2622

Macromolecular self-assembly

Macromolecular self-assembly is an important research direction toward advanced materials. The intrinsic multivalency effect of polymer materials and the emerging reversible deactivation radical polymerization (RDRP) technique enable us to design and engineer numerous macromolecule systems that can impact nanomedicine and programmable soft materials. Utilizing photoinitiated polymerization induced self-assembly (photo-PISA), we created peptide-brush polymer nanoparticles with ~50% loading of therapeutic peptides. The photo-PISA materials have enhanced cell uptake and higher apoptosis efficiency. Using macromolecules functionalized with self-reporting fluorophores, we successfully developed self-assembled polymer nanostructures in anisotropic environments like liquid crystal. Polymers that can self-assemble selectively in single topological defects of nematic liquid crystal could further be used as nanotemplates for directed synthesis and evolution with precise spatial manipulation. 

Keywords: Polymer Synthesis, Supramolecular Chemistry, Biomedicine, Programmable Soft Materials

Angew. Chem. Int. Ed. 2020, 59, 19136; Chem. Mater. 2020, 32, 6753

Pigment chemistry

Pigments are ubiquitous in modern society and biological systems. Designing exotic pigments and controlling their self-assembly behaviors could generate a myriad of functions, especially in mediating the interaction of photons with living systems. We created a fluorocarbon-hydrocarbon cyanine pigment that can form red-shifted J-aggregates in a fluorous solvent. Red-shifting fluorescence could facilitate bio-imaging with reduced autofluorescence and enhanced tissue penetration. Combining with orthogonal fluorous emulsion could enable imaging and sensing in living systems. We also engineered artificial melanin pigment with enhanced reactive oxygen species scavenging properties, which could protect primary skin keratinocyte cells against detrimental oxidative species generated by high-energy photons.

Keywords: Synthetic Pigment, Biological Pigment, Optical Sensing, Bio-imaging

J. Am. Chem. Soc. 2018, 140, 2727; Chem. Mater. 2020, 32, 5759