Surface functionalized drug loaded spinel ferrite MFe2O4 (M = Fe, Co, Ni, Zn) nanoparticles, their biocompatibility and cytotoxicity in vitro: A comparison

Sadaf Mushtaq; Khuram Shahzad; Tariq Saeed; Anwar Ul-Hamid; Bilal Haider Abbasi; Nafees Ahmad; Waqas Khalid; Muhammad Atif; Zulqurnain Ali; Rashda Abbasi

doi:10.3762/bxiv.2021.56.v1

Surface functionalized drug loaded spinel ferrite MFe₂O₄ (M = Fe, Co, Ni, Zn) nanoparticles, their biocompatibility and cytotoxicity in vitro: A comparison

Sadaf Mushtaq ,
Khuram Shahzad ,
Tariq Saeed ,
Anwar Ul-Hamid ,
Bilal Haider Abbasi ,
Nafees Ahmad ,
Waqas Khalid ,
Muhammad Atif ,
Zulqurnain Ali and
Rashda Abbasi

Submitting author affiliation:

Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan

Beilstein Arch. 2021, 202156. https://doi.org/10.3762/bxiv.2021.56.v1

Published 10 Aug 2021

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Read the peer-reviewed version of this preprint: https://doi.org/10.3762/bjnano.12.99

SUBJECT AREAS

Show All Preprints Nanotechnology Organic chemistry Bioorganic chemistry / chemical biology Catalysis Chemical methods and reactions Flow and process chemistry Green and sustainable chemistry Materials chemistry Medicinal and pharmaceutical chemistry Nano- and molecular-scale electronics Nano-biomaterials and bioscience Nanomagnetics Nanomaterials, thin films and nanointerfaces Nanomedicine Nanometrology and nanomechanics Nano-optics Nanopatterning, self-assembly and nanofabrication Nanostructures for energy and sensing applications Natural products chemistry Organo main group chemistry Other nanotechnology (unclassified) Other organic chemistry (unclassified) Photochemistry and photovoltaics Physical organic chemistry Supramolecular chemistry

Abstract

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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When a peer-reviewed version of this preprint is available, this information will be updated in the information box above. If no peer-reviewed version is available, please cite this preprint using the following information:

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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aromatic	the word “aromatic”
aromatic aldehyde	the word “aromatic” OR “aldehyde”
+aromatic +aldehyde	both words “aromatic” AND “aldehyde”
+aromatic -aldehyde	the word “aromatic” but NOT “aldehyde”
“aromatic aldehyde”	the exact phrase “aromatic aldehyde”
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benzyl~	words that are close to the word “benzyl”, such as “benzoyl” (i.e., fuzzy search)