Thermally controlled release of anticancer drug from self-assembled γ-substituted amphiphilic poly(ε-caprolactone) micellar nanoparticles.
A thermo-responsive poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone}-b-poly(γ-octyloxy-ε-caprolactone) (PMEEECL-b-POCTCL) diblock copolymer was synthesized by ring-opening polymerization using tin octanoate (Sn(Oct)(2)) catalyst and a fluorescent dansyl initiator. The PMEEECL-b-POCTCL had a lower critical solution temperature (LCST) of 38 °C, and it was employed to prepare thermally responsive micelles. Nile Red and Doxorubicin (DOX) were loaded into the micelles, and the micellar stability and drug carrying ability were investigated. The size and the morphology of the cargo-loaded micelles were determined by DLS, AFM, and TEM. The Nile-Red-loaded polymeric micelles were found to be stable in the presence of both fetal bovine serum and bovine serum albumin over a 72 h period and displayed thermo-responsive in vitro drug release. The blank micelles showed a low cytotoxicity. As comparison, the micelles loaded with DOX showed a much higher in vitro cytotoxicity against MCF-7 human breast cancer cell line when the incubation temperature was elevated above the LCST. Confocal laser scanning microscopy was used to study the cellular uptake and showed that the DOX-loaded micelles were internalized into the cells via an endocytosis pathway.
Department of Chemistry and Biochemistry & Nanocenter, University of South Carolina, Columbia, South Carolina 29208, United States.
Yixing
Y
Cheng
Jing
J
Hao
L Andrew
LA
Lee
Michael C
MC
Biewer
Qian
Q
Wang
Mihaela C
MC
Stefan
D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000494:pharmacology; D004339:Drug Compounding; D004705:Endocytosis; D005456:Fluorescent Dyes; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008027:Light; D008823:Micelles; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D053769:Nanocapsules; D010078:Oxazines; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D012542:Scattering, Radiation; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry*; D013696:Temperature
D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D005456:Fluorescent Dyes; D008823:Micelles; D053769:Nanocapsules; D010078:Oxazines; D011091:Polyesters; D013501:Surface-Active Agents; C016240:polycaprolactone; D004317:Doxorubicin; C044808:nile red