Thermoresponsive Supramolecular Chemotherapy by “V”‐Shaped Armed β‐Cyclodextrin Star Polymer to Overcome Drug Resistance

Abstract

Pump mediated drug efflux is the key reason to result in the failure of chemotherapy. Herein, a novel star polymer β-CD-v-(PEG-β-PNIPAAm) consisting of a β-CD core, grafted with thermo-responsive poly(N-isopropylacrylamide) (PNIPAAm) and biocompatible poly(ethylene glycol) (PEG) in the multiple "V"-shaped arms is designed and further fabricated into supramolecular nanocarriers for drug resistant cancer therapy. The star polymer could encapsulate chemotherapeutics between β-cyclodextrin and anti-cancer drug via inclusion complex (IC). Furthermore, the temperature induced chain association of PNIPAAm segments facilitated the IC to form supramolecular nanoparticles at 37 °C, whereas the presence of PEG impart great stability to the self-assemblies. When incubated with MDR-1 membrane pump regulated drug resistant tumor cells, much higher and faster cellular uptake of the supramolecular nanoparticles were detected, and the enhanced intracellular retention of drugs could lead to significant inhibition of cell growth. Further in vivo evaluation showed high therapeutic efficacy in suppressing drug resistant tumor growth without a significant impact on the normal functions of main organs. This work signifies thermo-responsive supramolecular chemotherapy is promising in combating pump mediated drug resistance in both in vitro and in vivo models, which may be encouraging for the advanced drug delivery platform design to overcome drug resistant cancer.

Linear Chimeric Triblock Molecules Self‐Assembled Micelles with Controllably Transformable Property to Enhance Tumor Retention for Chemo‐Photodynamic Therapy of Breast Cancer

“…However, when compared with the laser‐off group, the laser‐on group showed notably stronger accumulations in both the marginal and the internal areas, suggesting the specific shape change triggered by irradiation could enhance the retention of nanomedicine. These data systematically validated that, although free hydrophobic drugs showed extreme performance at the cell level as measured by the cytotoxic studies, their distributive manners remain concerned in the organic body . On the contrary, after loading onto PTX 2 ‐TK@Ce6/BR‐FFVLK‐PEG, their distributive behaviors changed, possessing more opportunities to exhibit therapeutic activities.…”

Precise Synthesis of PS‐PLA Janus Star‐Like Copolymer

“…Synthesis of novel macromolecular architecture with well‐defined structures and compositions has been an important research topic in polymer science . Thanks to the advances in polymerization techniques, numerous well‐organized polymers have been prepared over the past few decades . One of these structures is the Janus particle having biphasic geometry of distinct compositions and properties, first coined by Pierre‐Gilles de Gennes in his Nobel Prize address .…”

Organic Nanocarriers for Delivery and Targeting of Therapeutic Agents for Cancer Treatment

“…At the temperature above LCST, PNIPAAm chains became hydrophobic and its intermolecular associations promoted drug‐loaded star polymers to form supramolecular NPs formation. PEG chains favored the cellular uptake of the inclusion complexes and enhanced drug delivery to MDR1 drug‐resistant cancer cells . Zhang and coworkers have developed a novel Y‐shaped thermosensitive amphiphilic copolymer comprised of two hydrophobic segments from poly(oleic acid) and hydrophilic PNIPAAm segment.…”