Hierarchically Self-Assembled Supramolecular Host–Guest Delivery System for Drug Resistant Cancer Therapy

Abstract

In this report, a new star-like copolymer β-CD- g-(PNIPAAm- b-POEGA) , consisting of a β-CD core, grafted with temperature-responsive poly( N-isopropylacrylamide) (PNIPAAm) and biocompatible poly(oligo(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- g-(PNIPAAm- b-POEGA)/PTX inclusion complex to hierarchically self-assemble into nanosized supramolecular assemblies at 37 °C, whereas the presence of poly(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 in vivo 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 in vitro and in vivo models, which is of significant importance for the advanced drug delivery platform designed to combat drug resistant cancer.

A Recent Perspective on Noncovalently Formed Polymeric Hydrogels

“…We found that PEO conjugated to tetraphenylethene (TPE) normally leads to aggregation‐induced emission, and addition of α‐CD leads to a 4–12 fold increase of fluorescence, possibly due to α‐CD restriction on TPE segment rotation . Supramolecular assemblies based on either α‐CD or β‐CD were used in conjunction with cationic copolymer for sustained delivery of Bcl‐2 DNA and combined with temperature‐responsive polymers to deliver the chemotherapeutic paclitaxel ,. Building on the concept of reversible host‐guest complexation, stimuli‐responsive sol‐gel switching materials were designed.…”

Recent Progress in Polyhydroxyalkanoates‐Based Copolymers for Biomedical Applications

“…This amphiphilic PHB‐based polymer might self‐assembly into nanoparticles and for HepaRG cells uptake, which can be utilized for a feasible drug delivery vehicle . Poly(2‐dimethylamino‐ethyl methacrylate) (PDMAEMA) with thermal sensitivity is often used as block of temperature sensitive drug delivery vehicles . For example, comb‐shaped copolymers made up of 3‐hydroxy‐9‐decenoate (3H9D), or 3‐hydroxydodecanoate (3HDD), with graft of PDMAEMA were utilized for preparing PDMAEMA oligomers with uniform “side chains,” followed by aminolysis at the end of which a sulfhydryl group and final activation of thiol‐containing PDMAEMA.…”

Polymeric Janus Nanoparticles: Recent Advances in Synthetic Strategies, Materials Properties, and Applications

“…It is well‐known that block copolymer can self‐assemble into distinct domains in selected solvents or in the bulk state . Due to this unique properties, various types of microphase‐separated structures, including cylinders, spheres, lamellae, or gyroids have been reported .…”