Abstract

The purpose of our study was to develop new delivery systems for drugs effective against breast cancer by using biodegradable and biocompatible capsules. Redox-active microcapsules based on thiolated polymethacrylic acid (PMA) were employed. The interaction of these PMASH capsules with breast cancer cells and the mechanism of their internalization was investigated. PMASH biocompatibility was evaluated by MTT assay. To analyze their potential as drug carrier, we incorporated doxorubicin into the capsules. Confocal microscopy observations showed the presence of capsules inside the cells. Although some drug molecules still appeared co-localized with PMASH capsules, strong doxorubicin fluorescence was observed both in the cytoplasm and nucleus, indicating the disassembling of the capsule into PMASH-drug conjugate after internalization. These results were confirmed by both flow cytometry (time course of capsule uptake) and scanning electron microscopy. PMASH capsules were also internalized in 3D cell structures (spheroids) suggesting their potential use as drug delivery system for treatment of human diseases.

Highlights

  • Breast cancer is the most frequent type of malignancy and the leading cause of cancer deaths of women in developed countries; it constitutes 23% of total cancer cases and 14% of the cancer deaths [1]

  • To evaluate the potential use of Thiolated Poly Capsules (PMASH)-DOX capsules as in vitro delivery system for breast cancer cells, the effect of thiolated poly(methacrylic acid) and PMASH capsules on cell growth and viability was analyzed by MTT assay

  • In order to evaluate the potential of PMASH capsules as a carrier to deliver anticancer drugs, DOX was covalently linked into the capsules

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Summary

Introduction

Breast cancer is the most frequent type of malignancy and the leading cause of cancer deaths of women in developed countries; it constitutes 23% of total cancer cases and 14% of the cancer deaths [1]. Up to 7% of breast cancers are being diagnosed in women less than 40 years old years and less than 4% in women below the age of 35 years [2]. Chemotherapeutic agents currently approved for breast cancer treatment include several drugs (anthracyclines, alkylating agents, platinum drugs, taxanes, vinca alkaloids) (NIH, National Cancer Institute, http:// www.cancer.gov/about-cancer/treatment/drugs/breast). They often show lack of selectivity or specificity toward cancer cells, resulting in several side effects [4]

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