Biocompatibility and cytotoxicity in vitro of surface-functionalized drug-loaded spinel ferrite nanoparticles

作者：Sadaf Mushtaq, Khuram Shahzad, Tariq Saeed, Anwar Ul‐Hamid, Bilal Haider Abbasi, Nafees Ahmad, Waqas Khalid, M. Atif, Zulqurnain Ali, Rashda Abbasi · 发表于：Beilstein Journal of Nanotechnology · 年份：2021 · DOI：10.3762/bjnano.12.99 · 被引用次数：29 · 研究领域：Nanoparticle-Based Drug Delivery、Magnetic Properties and Synthesis of Ferrites、Nanomaterials for catalytic reactions

In this study, poly(isobutylene- alt -maleic anhydride) (PMA)-coated spinel ferrite (MFe 2 O 4 , where M = Fe, Co, Ni, or Zn) nanoparticles (NPs) were developed as carriers of the anticancer drugs doxorubicin (DOX) and methotrexate (MTX). Physical characterizations confirmed the formation of pure cubic structures (14–22 nm) with magnetic properties. Drug-loaded NPs exhibited tumor specificity with significantly higher ( p < 0.005) drug release in an acidic environment (pH 5.5). The nanoparticles were highly colloidal (zeta potential = −35 to −26 mV) in deionized water, phosphate buffer saline (PBS), and sodium borate buffer (SBB). They showed elevated and dose-dependent cytotoxicity in vitro compared to free drug controls. The IC 50 values ranged from 0.81 to 3.97 μg/mL for HepG2 and HT144 cells, whereas IC 50 values for normal lymphocytes were 10 to 35 times higher (18.35–43.04 µg/mL). Cobalt ferrite (CFO) and zinc ferrite (ZFO) NPs were highly genotoxic ( p < 0.05) in cancer cell lines. The nanoparticles caused cytotoxicity via oxidative stress, causing DNA damage and activation of p53-mediated cell cycle arrest (significantly elevated expression, p < 0.005, majorly G1 and G2/M arrest) and apoptosis. Cytotoxicity testing in 3D spheroids showed significant ( p < 0.05) reduction in spheroid diameter and up to 74 ± 8.9% of cell death after two weeks. In addition, they also inhibited multidrug resistance (MDR) pump activity in both cell lines suggesting effectivity ...