Hydrophobization of Ribonucleic Acids for Facile Systemic Delivery and Multifaceted Cancer Immunotherapy

Abstract

Ribonucleic acids (RNAs) enable disease-related gene inhibition, expression, and editing and represent promising therapeutics in various diseases. The efficacy of RNA relies heavily on the presence of a secure and effective delivery system. Herein, we found that RNA could be hydrophobized by cationic lipid and ionizable lipid and conveniently coassemble with amphiphilic polymer to achieve micelle-like nanoparticles (MNP). The results of the study indicate that MNP exhibits a high level of efficiency in delivering RNA. Besides, the MNP encapsulating siRNA that targets CD47 and PD-L1 remarkably blocked these immune checkpoints in a melanoma tumor model and elicited a robust immune response. Moreover, the MNP encapsulating the mRNA of OVA achieved antigen translation and presentation, leading to an effective antitumor immunoprophylaxis outcome against OVA-expressing melanoma model. Our findings suggest that RNA hydrophobization could serve as a viable approach for delivering RNA, thereby facilitating the exploration of RNA therapy in disease treatment.

Optimization of lipid assisted polymeric nanoparticles for siRNA delivery and cancer immunotherapy

“…Previously, we utilized a poly(ethylene glycol)- b -poly( d , l -lactide) and cationic lipid combination to encapsulate siRNA, 19–23 employing a double emulsion–solvent evaporation technique. This approach yielded exceptional siRNA loading efficiency, exceeding 95%, owing to its nanoconfined loading mechanism.…”

Robust anti-tumor immunity through the integration of targeted lipid nanoparticle-based mRNA nanovaccines with PD-1/PD-L1 blockade

“…Tumor cells cunningly evade the immune surveillance of the body through an intricate network structure, which grants them the ability to proliferate, replicate, migrate, infiltrate, and ultimately metastasize [ 28 ]. Immune checkpoint inhibitor (ICI) therapy has emerged as one of the most widely utilized tumor immunotherapy approaches, aimed at reshaping the immunosuppressive microenvironment by blocking immune checkpoints [ [29] , [30] , [31] ]. In 2011, the FDA approved the first inhibitor specifically targeting the immune checkpoint CTLA-4, the monoclonal drug ipilimumab, for use in immunotherapy against advanced melanoma [ 32 ].…”