Abstract
Despite the considerable progress made in the field of anticancer nanomedicine, the influence of the physicochemical characteristics of the nanoconstructs on their internalization and cytotoxicity towards specific cancer cells remains to be fully understood. The aim of this in vitro study was to examine the factors influencing the potency of styrene maleic acid (SMA-Dox) micelles loaded with doxorubicin in a range of 4.4% to 28.4% using breast cancer and prostate cancer cell lines. A significant difference in cytotoxicity relative to micelle loading was observed and correlated with the expression level of caveolin-1. The expression level of caveolin-1 has previously been associated with advanced, aggressive cancer subtypes. For example, SMA-Dox micelles were shown to co-localize with caveolin-1 in PC3 cells and this colocalization was disrupted by treatment with the caveolin-1 inhibitor, genistein. The results of this study are indicative that the micelle loading and cellular expression of caveolin-1 modulates the relative cytotoxicity of nanoconstructs of different loading against breast and prostate cancer cell lines in vitro. The expression level of caveolin-1 is a factor to consider when developing nanoconstructs for the treatment of breast and prostate cancers.
Highlights
The use of nanomedicine for the treatment of cancer has been a promising field for the past 25 years but, despite promising efficacy in animal studies, only nine nanomedicines have successfully transition to the clinics and approved for the treatment of various cancers [1]
PC3, MDA-MB-231, DU145 and MCF-7 cells were obtained from the American type culture collection (ATCC), Manassas USA and all experiments were conducted with cells below passage 30
We confirmed that the drug was not altered by the encapsulation by the comparison of spectra of the encapsulated versus free doxorubicin
Summary
The use of nanomedicine for the treatment of cancer has been a promising field for the past 25 years but, despite promising efficacy in animal studies, only nine nanomedicines have successfully transition to the clinics and approved for the treatment of various cancers [1]. The micelles had a weight/weight loading of 4.4, 14.5, and 28.4% doxorubicin and were assessed based on their relative toxicity towards breast and prostate cancer cell lines.
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