The novel self-assembling bottlebrush
polyethylene glycol-
polynorbornene-thiocresol block copolymers (PEG-PNB-TC) were synthesized by the ring opening metathesis polymerization (ROMP), followed by functionalization of the
polymer backbone via the thio-bromo "click" postpolymerization strategy. The PEG-PNB-TC copolymers could easily self-assemble into the nanoscale core-shell polymeric
micelles. The hydrophobic anticancer drugs, such as
paclitaxel (PTX), could be loaded into their hydrophobic core to form a stable drug-loaded
micelle with a superior drug loading capacity of up to ∼35% (w/w). The sustained drug release behavior of the PEG-PNB-TC
micelles was observed under a simulated "sink condition". Compared with commercial PTX formulation (
Taxol), the PTX-loaded PEG-PNB-TC
micelles showed the enhanced in vitro cellular uptake and comparable cytotoxicity in the drug-sensitive
cancer cells, while the copolymers were much safer than
Cremophor EL, the
surfactant used in
Taxol. Furthermore,
curcumin (CUR), a natural
chemotherapy drug sensitizer, was successfully coloaded with PTX into the PEG-PNB-TC
micelles. High drug loading capacity of the PEG-PNB-TC
micelles allowed for easy adjustment of drug doses and the ratio of the coloaded drugs. The combination of PTX and CUR showed synergistic anticancer effect in both the drug mixture and drug coloaded
micelles at high CUR/PTX ratio, while low CRU/PTX ratio only exhibited additive effects. The combinatorial effects remarkably circumvented the PTX resistance in the multidrug resistant (MDR)
cancer cells. Due to the easy polymerization and functionalization, excellent self-assembly capability, high drug loading capability, and great stability, the PEG-PNB-TC copolymers might be a promising nanomaterial for delivery of the hydrophobic anticancer drugs, especially for
combination drug therapy.