1 research outputs found
Hierarchically Self-Assembled Supramolecular Host–Guest Delivery System for Drug Resistant Cancer Therapy
In
this report, a new star-like copolymer β-CD-<i>g</i>-(PNIPAAm-<i>b</i>-POEGA)<sub><i>x</i></sub>,
consisting of a β-CD core, grafted with temperature-responsive
polyÂ(<i>N</i>-isopropylacrylamide) (PNIPAAm) and biocompatible
polyÂ(oligoÂ(ethylene glycol) acrylate) (POEGA) in a block copolymer
of the arms, was used to deliver chemotherapeutics to drug resistant
cancer cells and tumors. The first step of the self-assembly process
involves the encapsulation of chemotherapeutics through host–guest
inclusion complexation between the β-cyclodextrin cavity and
the anticancer drug. Next, the chain interaction of the PNIPAAm segment
at elevated temperature drives the drug-loaded β-CD-<i>g</i>-(PNIPAAm-<i>b</i>-POEGA)<sub><i>x</i></sub>/PTX inclusion complex to hierarchically self-assemble into
nanosized supramolecular assemblies at 37 °C, whereas the presence
of polyÂ(ethylene glycol) (PEG) chains in the distal end of the star-like
copolymer arms impart enhanced stability to the self-assembled structure.
More interestingly, this supramolecular host–guest nanocomplex
promoted the enhanced cellular uptake of chemotherapeutics in MDR-1
up-regulated drug resistant cancer cells and exhibited high therapeutic
efficacy for suppressing drug resistant tumor growth in an <i>in vivo</i> mouse model, due to the increased stability, improvement
in aqueous solubility, enhanced cellular uptake, and partial membrane
pump impairment by taking the advantage of PEGylation and supramolecular
complex between this star-like copolymer and chemotherapeutics. This
work signifies that temperature-sensitive PEGylated supramolecular
nanocarriers with good biocompatibility are effective in combating
MDR-1 mediated drug resistance in both <i>in vitro</i> and <i>in vivo</i> models, which is of significant importance for the
advanced drug delivery platform designed to combat drug resistant
cancer