In this study, polymer coated biocompatible MFe2O4 (M=Fe, Co, Ni, Zn) NPs were developed as carriers of anticancer drugs. Synthesized NPs were characterized via XRD, TEM, EDS and PPMS which confirmed formation of pure cubic structures (14 - 22 nm) with magnetic properties. The anticancer drugs: doxorubicin (DOX) and methotrexate (MTX) loaded NPs exhibited tumor specificity with significantly higher (p<0.005) drug release in acidic pH 5.5. NPs were highly colloidal in deionized water, PBS and SBB (-35 to -26 mV). They showed elevated and dose dependent cytotoxicity in vitro compared to free drug controls. IC50 values ranged from 0.81 - 3.97 mg/ml against HepG2 and HT144 cells. On the contrary, IC50 values for normal lymphocytes were 10 to 35 times higher (18.35 - 43.04 mg/ml). CFO and ZFO nanocarriers were highly genotoxic (p<0.05) against both cancer cell lines. NPs caused cytotoxicity via oxidative stress, causing DNA damage and activation of p53 (significantly elevated expression, p<0.005) mediated cell cycle arrest (majorly G1 and G2/M arrest) and apoptosis. When tested for cytotoxicity in 3D spheroids, they showed significant (p<0.05) reduction in spheroid diameter and upto 74 ± 8.9% cell death after 2 weeks. In addition, they also inhibited MDR pump activity in both cell lines suggesting their potential to combat multidrug resistance in cancers. Among tested MFe2O4 NPs, CFO nanocarriers were most favorable for targeted cancer therapy due to excellent magnetic, colloidal, cytotoxic, and biocompatible aspects. However, detailed investigations of molecular pathways involved, in vivo cytotoxicity and magnetic field assisted experiments are needed to fully exploit them in therapeutic domains.
Keywords: Magnetic spinel ferrite nanoparticles; polyisobutylene-alt-maleic anhydride; drug carriers; doxorubicin; methotrexate; in vitro
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Mushtaq, S.; Shahzad, K.; Saeed, T.; Ul-Hamid, A.; Abbasi, B. H.; Ahmad, N.; Khalid, W.; Atif, M.; Ali, Z.; Abbasi, R. Beilstein Arch. 2021, 202156. doi:10.3762/bxiv.2021.56.v1
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