Journal
MOLECULAR PHARMACEUTICS
Volume 13, Issue 12, Pages 4021-4033Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.6b00362
Keywords
polymeric micelles; terpolymer; drug delivery; arsenite; arsenic trioxide; cancer
Funding
- Canadian Institutes of Health Research
- Canada Research Chairs Program
- Natural Sciences and Engineering Research Council of Canada
- Alberta Health
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In this study, we developed a micellar platform composed of terpolymers for the encapsulation of inorganic arsenite or arsenous acid (As-III). For this purpose, a series of terpolymers composed of poly(ethylene oxide) (PEO, block A), poly(alpha-carboxylate-epsilon-carprolactone) (PCCL, block B), and poly(epsilon-caprolactone) (PCL, block C) with either a blocked, i.e., BC or CB, or random, i.e., (B/C)(ran) block copolymer sequence in the polyester segment was synthesized. The COOH groups on block B were further modified with mercaptohexylamine for As-III encapsulation. 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., As-III, by MDA-MB-435 cancer cells. H-1 NMR spectroscopy in D2O and CDCl3 was 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)(ran) as reflected by a lower critical micellar concentration. The As-III- 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 As-III by 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 As-III delivery compared to ACB and A(B/C)(ran) micelles
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