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Polyprodrug Amphiphiles: Hierarchical Assemblies for Shape-Regulated Cellular Internalization, Trafficking, and Drug Delivery
journal contribution
posted on 2013-11-20, 00:00 authored by Xianglong Hu, Jinming Hu, Jie Tian, Zhishen Ge, Guoying Zhang, Kaifu Luo, Shiyong LiuSolution
self-assembly of block copolymers (BCPs) typically generates
spheres, rods, and vesicles. The reproducible bottom-up fabrication
of stable planar nanostructures remains elusive due to their tendency
to bend into closed bilayers. This morphological vacancy renders the
study of shape effects on BCP nanocarrier-cell interactions incomplete.
Furthermore, the fabrication of single BCP assemblies with built-in
drug delivery functions and geometry-optimized performance remains
a major challenge. We demonstrate that PEG-b-PCPTM
polyprodrug amphiphiles, where PEG is poly(ethylene glycol) and PCPTM
is polymerized block of reduction-cleavable camptothecin (CPT) prodrug
monomer, with >50 wt % CPT loading content can self-assemble into
four types of uniform nanostructures including spheres, large compound
vesicles, smooth disks, and unprecedented staggered lamellae with
spiked periphery. Staggered lamellae outperform the other three nanostructure
types, exhibiting extended blood circulation duration, the fastest
cellular uptake, and unique internalization pathways. We also explore
shape-modulated CPT release kinetics, nanostructure degradation, and
in vitro cytotoxicities. The controlled hierarchical organization
of polyprodrug amphiphiles and shape-tunable biological performance
opens up new horizons for exploring next-generation BCP-based drug
delivery systems with improved efficacy.
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drug delivery functionsprodrug monomernanostructure typescompound vesiclesblood circulation durationPEGnanostructure degradationuniform nanostructurespolymerized blockPCPTM polyprodrug amphiphilesBCP assembliespolyprodrug amphiphilesinternalization pathwaysStaggered lamellaeHierarchical AssembliesperformancePolyprodrug Amphiphilesblock copolymersfabricationshape effects
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