Polyprodrug
Amphiphiles: Hierarchical Assemblies for
Shape-Regulated Cellular Internalization, Trafficking, and Drug Delivery
Xianglong Hu
Jinming Hu
Jie Tian
Zhishen Ge
Guoying Zhang
Kaifu Luo
Shiyong Liu
10.1021/ja409686x.s001
https://acs.figshare.com/articles/journal_contribution/Polyprodrug_Amphiphiles_Hierarchical_Assemblies_for_Shape_Regulated_Cellular_Internalization_Trafficking_and_Drug_Delivery/2351437
Solution
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-<i>b</i>-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.
2013-11-20 00:00:00
drug delivery functions
prodrug monomer
nanostructure types
compound vesicles
blood circulation duration
PEG
nanostructure degradation
uniform nanostructures
polymerized block
PCPTM polyprodrug amphiphiles
BCP assemblies
polyprodrug amphiphiles
internalization pathways
Staggered lamellae
Hierarchical Assemblies
performance
Polyprodrug Amphiphiles
block copolymers
fabrication
shape effects