Synergic fabrication of folic acid-targeted hyperbranched polymer (HBP)-modified pH-response drug delivery system for the treatment of breast cancer

Abstract

As vectors for anticancer drug delivery, mesoporous silica nanocomposites (MSN) incorporated bicalutamide (BLT) featuring folic acid (FA) (termed as COOH-MSNs-HBP@BLT/FA) have been effectively achieved due to their ability to pH stimulation response and targeting. Systematic characterization investigations were conducted to determine the chemical composition and physical characteristics of these NPs. Through carboxy alteration, their drug loading capacity was dramatically increased (268.60 %), and they displayed pH-responsive drug release patterns. Additionally, the cytotoxicity of the as-synthesized NPs was tested in MDA-MB-231 and MCF-7 cells in vitro. After 24-h of treatment with BLT, COOH-MSNs, COOH-MSNs@BLT, COOH-MSNs-HBP@BLT/FA, MCF-7, and MDA-MB-231 cells exhibited distinct morphological alterations, and reddish orange apoptotic bodies were detected using acridine orange and ethidium bromide (AO and EB) double staining. Nuclear alterations such as chromatin condensation/fragmentation were detected by Hoechst 33342 staining techniques. The Annexin V-FITC/PI was used to examine the apoptosis mechanism of the cells. These results prove that apoptosis induction is responsible for the antiproliferative effects of BLT, COOH-MSNs, COOH-MSNs@BLT, and COOH-MSNs-HBP@BLT/FA in MCF-7 and MDA-MB-231cells. We conclude that COOH-MSNs-HBP@BLT/FA has the potential as a drug delivery method for breast cancer treatment.