Multimodal Nanoparticle

Multimodal Fluorogenic Nanoparticles as Analytic Tools to Study Endosomal Escape

For more than 40 years, endosomal escape has remained the major bottleneck in nanomedicine including the recent success of RNA therapeutics. Unlike small-molecule drugs, most biologics are too large, too charged, and too hydrophilic to passively diffuse across the cell membrane. It has been shown that ~99% of RNA therapeutics are entrapped and retained in endosomes. Endosomal escape remains the rate-limiting delivery problem, and determining the mechanisms involved in endosomal escape has been technically challenging. Methods to improve endosomal rupture/escape and techniques to visualize escape have been explored, but they all focus on measuring the escaped nanomaterial or payload. To understand and visualize endosomal escape from a different perspective, we are interested in developing multimodal fluorogenic nanoparticles to visualize the integrity of drug carriers, such as breakdown of LNPs in endosomes.  

Relevant Papers:​ J. Am. Chem. Soc. 2018, 140, 9468–9493. Org. Biomol. Chem. 2020, 18, 5747–5763.  Method. Enzymol. 2020, 640, 309–326.