Terpolymer Micelles for the Delivery of Arsenic to Breast Cancer Cells: The Effect of Chain Sequence on Polymeric Micellar Characteristics and Cancer Cell Uptake.
In this study, we developed a micellar platform composed of terpolymers for the encapsulation of inorganic arsenite or arsenous acid (AsIII). For this purpose, a series of terpolymers composed of poly(ethylene oxide) (PEO, block A), poly(α-carboxylate-ε-carprolactone) (PCCL, block B), and poly(ε-caprolactone) (PCL, block C) with either a blocked, i.e., BC or CB, or random, i.e., (B/C)ranblock copolymer sequence in the polyester segment was synthesized. The COOH groups on block B were further modified with mercaptohexylamine for AsIIIencapsulation. We then investigated how sequence of terpolymers can affect the stability and surface charge of micelles as well as the cellular uptake of their cargo, i.e., AsIII, by MDA-MB-435 cancer cells.1H NMR spectroscopy in D2O and CDCl3was also used to study the structure of different terpolymer micelles. Our results showed micelles with ABC sequence to have better stability over those of ACB and A(B/C)ranas reflected by a lower critical micellar concentration. The AsIII-loaded ABC micelles were less negatively charged on the surface than the other two types of terpolymer micelles. In line with this observation, ABC micelles showed a substantially enhanced uptake of AsIIIby MDA-MB-435 cancer cells. Stability and surface charge are key parameters that can influence the performance of polymeric micelles as nanodrug carriers. Based on these results, we suggest ABC micelles to have improved characteristics for AsIIIdelivery compared to ACB and A(B/C)ranmicelles.
Faculty of Medicine and Dentistry, Department of Laboratory Medicine and Pathology, Division of Analytical and Environmental Toxicology, University of Alberta , Edmonton, Alberta T6G 2G3, Canada.
Qi
Q
Zhang
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta , Edmonton, Alberta T6G 2E1, Canada.
Mohammad Reza
MR
Vakili
Faculty of Medicine and Dentistry, Department of Laboratory Medicine and Pathology, Division of Analytical and Environmental Toxicology, University of Alberta , Edmonton, Alberta T6G 2G3, Canada.
Xing-Fang
XF
Li
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta , Edmonton, Alberta T6G 2E1, Canada.
Afsaneh
A
Lavasanifar
Faculty of Medicine and Dentistry, Department of Laboratory Medicine and Pathology, Division of Analytical and Environmental Toxicology, University of Alberta , Edmonton, Alberta T6G 2G3, Canada.
X Chris
XC
Le
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001151:Arsenic / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008823:Micelles; D011108:Polymers / Q000737:chemistry*
D000970:Antineoplastic Agents; D008823:Micelles; D011108:Polymers; D001151:Arsenic
arsenic trioxide; arsenite; cancer; drug delivery; polymeric micelles; terpolymer