Lipid–polymer hybrid nanoparticles as a next-generation drug delivery platform: state of the art, emerging technologies, and perspectives

Anubhab Mukherjee,1,2 Ariana K Waters,1,2 Pranav Kalyan,3 Achal Singh Achrol,2 Santosh Kesari,2 Venkata Mahidhar Yenugonda1,2 1Drug Discovery and Nanomedicine Research Program, 2Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Pacific Neuroscience Institute, Providence Saint John’s Health Center, Santa Monica, CA, USA; 3Agoura High School, Agoura Hills, CA, USA Abstract: Lipid–polymer hybrid nanoparticles (LPHNPs) are next-generation core–shell nanostructures, conceptually derived from both liposome and polymeric nanoparticles (NPs), where a polymer core remains enveloped by a lipid layer. Although they have garnered significant interest, they remain not yet widely exploited or ubiquitous. Recently, a fundamental transformation has occurred in the preparation of LPHNPs, characterized by a transition from a two-step to a one-step strategy, involving synchronous self-assembly of polymers and lipids. Owing to its two-in-one structure, this approach is of particular interest as a combinatorial drug delivery platform in oncology. In particular, the outer surface can be decorated in multifarious ways for active targeting of anticancer therapy, delivery of DNA or RNA materials, and use as a diagnostic imaging agent. This review will provide an update on recent key advancements in design, synthesis, and bioactivity evaluation as well as discussion of future clinical possibilities of LPHNPs. Keywords: lipid–polymer hybrid nanoparticle, lipid-based nanoparticle, polymer-based nanoparticles, drug delivery, gene delivery