title: Multiscale approach to investigate self-assembly of telodendrimer based nanocarriers for anticancer drug delivery.
abstract: Delivery of poorly soluble anticancer drugs can be achieved by employing polymeric drug delivery systems, capable of forming stable self-assembled nanocarriers with drug encapsulated within their hydrophobic cores. Computational investigations can aid the design of efficient drug-delivery platforms; however, simulations of nanocarrier self-assembly process are challenging due to high computational cost associated with the large system sizes (millions of atoms) and long time scales required for equilibration. In this work, we overcome this challenge by employing a multiscale computational approach in conjunction with experiments to analyze the role of the individual building blocks in the self-assembly of a highly tunable linear poly(ethylene glycol)-b-dendritic oligo(cholic acid) block copolymer called telodendrimer. The multiscale approach involved developing a coarse grained description of the telodendrimer, performing simulations over several microseconds to capture the self-assembly process, followed by reverse mapping of the coarse grained system to atomistic representation for structural analysis. Overcoming the computational bottleneck allowed us to run multiple self-assembly simulations and determine average size, drug-telodendrimer micellar stoichiometry, optimal drug loading capacity, and atomistic details such hydrogen-bonding and solvent accessible area of the nanocarrier. Computed results are in agreement with the experimental data, highlighting the success of the multiscale approach applied here.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Jiang
authors.affiliation: †Department of Pharmacology, Upstate Cancer Research Institute, State University of New York Upstate Medical University, Syracuse, New York 13210, United States.
authors.forename: Juntao
authors.initials: J
authors.lastname: Luo
authors.forename: Shikha
authors.initials: S
authors.lastname: Nangia
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D019826:Cholic Acid / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D008823:Micelles; D008958:Models, Molecular; D008968:Molecular Conformation; D017239:Paclitaxel / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D004337:Drug Carriers; D008823:Micelles; D011092:Polyethylene Glycols; D019826:Cholic Acid; D017239:Paclitaxel