Poster abstracts
Poster number 6 submitted by Daniel Binzel
Conversion of Chemical Drugs into Targeting Ligands on RNA Nanoparticles and Assessing Payload Stoichiometry for Optimal Biodistribution in Cancer Treatment
Daniel W Binzel (Center for RNA Nanobiotechnology and Nanomedicine; Division of Pharmaceutics and Pharmacology, College of Pharmacy; and Comprehensive Cancer Center. The Ohio State University, Columbus, Ohio 43210, U), Congcong Xu (Center for RNA Nanobiotechnology and Nanomedicine; Division of Pharmaceutics and Pharmacology, College of Pharmacy; and Comprehensive Cancer Center. The Ohio State University, Columbus, Ohio 43210, U), Hongran Yin (Center for RNA Nanobiotechnology and Nanomedicine; Division of Pharmaceutics and Pharmacology, College of Pharmacy; and Comprehensive Cancer Center. The Ohio State University, Columbus, Ohio 43210, U), Tesla Yudhistira (Center for RNA Nanobiotechnology and Nanomedicine; Division of Pharmaceutics and Pharmacology, College of Pharmacy; and Comprehensive Cancer Center. The Ohio State University, Columbus, Ohio 43210, U), Hanna Lingren (Center for RNA Nanobiotechnology and Nanomedicine; Division of Pharmaceutics and Pharmacology, College of Pharmacy; and Comprehensive Cancer Center. The Ohio State University, Columbus, Ohio 43210, U), Peixuan Guo (Center for RNA Nanobiotechnology and Nanomedicine; Division of Pharmaceutics and Pharmacology, College of Pharmacy; and Comprehensive Cancer Center. The Ohio State University, Columbus, Ohio 43210, U)
Abstract:
Targeted drug delivery using nanoparticles has considerable potential for cancer treatment. However, biological barriers pose a challenge for nanoparticles to achieve active targeting, resulting in fast clearance or organ accumulation in vivo. RNA nanoparticles have demonstrated rapid spontaneous tumor targeting and very little organ accumulation due to rapid renal clearance of non-tumor accumulated RNA nanoparticles. To provide specific tumor accumulation, here a multivalent targeting strategy on RNA nanoparticles to control their in vivo fate is implemented. Methotrexate (MTX), a clinically approved chemotherapy was selected to serve as a tumor-targeting ligand through conjugation to our RNA nanoparticle, with controlled conjugation of various copy numbers. As copies of conjugated MTX increased on the RNA nanoparticle, the specific binding to folate receptor overexpressed by cancer cells was enhanced as demonstrated by flow cytometry analysis and confocal microscopy imaging. Increasing the amounts of conjugated MTX did not significantly change nanoparticle size, Zeta potential, or cytokine induction. Increased amounts of conjugated MTX resulted in improved cell inhibition due to MTX release following cell internalization. However, increasing conjugated MTX to the RNA nanoparticles reduced the melting temperature of RNA nanoparticles and increased in vitro serum protein binding to the nanoparticles. Thus, in vivo biodistribution profiles of RNA nanoparticles revealed different behaviors based on MTX conjugation in cancer targeting and clearance. By increasing the copies of MTX changed the ability of nanoparticles to target tumors, accumulate in healthy organs, and rapidly clear through the urine. Nanoparticle design must be closely considered for optimizing cancer targeting and therapy, providing the rationale for a proper design of RNA nanodelivery in cancer treatment.
References:
Xu C, Yin H, Yudhistira T, Li Z, Binzel DW, Guo P. Conversion of Chemical Drugs into Targeting Ligands on RNA Nanoparticles and Assessing Payload Stoichiometry for Optimal Biodistribution in Cancer Treatment. RNA Nanomed. 2024;1(1):109-123.
Keywords: RNA Nanotechnology, Cancer Targeting, Biodistribution