Combination of ovalbumin-coated iron oxide nanoparticles and poly(amidoamine) dendrimer-cisplatin nanocomplex for enhanced anticancer efficacy

Tefera Worku Mekonnen; Haile Fentahun Darge; Hsieh-Chih Tsai; Yihenew Simegniew Birhan; Endiries Yibru Hanurry; Hailemichael Tegenu Gebrie; Hsiao-Ying Chou; Juin-Yih Lai; Shinn-Zong Lin; Horng-Jyh Harn; Yu-Shuan Chen

doi:10.1016/j.colsurfb.2022.112391

Combination of ovalbumin-coated iron oxide nanoparticles and poly(amidoamine) dendrimer-cisplatin nanocomplex for enhanced anticancer efficacy

Colloids Surf B Biointerfaces. 2022 May:213:112391. doi: 10.1016/j.colsurfb.2022.112391. Epub 2022 Feb 4.

Affiliations

¹ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC.
² Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC; Advanced Membrane Materials Center, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC; R&D Center for Membrane Technology, Chung Yuan Christian University, Chungli, Taoyuan 320, Taiwan, ROC. Electronic address: h.c.tsai@mail.ntust.edu.tw.
³ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC; Advanced Membrane Materials Center, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC; R&D Center for Membrane Technology, Chung Yuan Christian University, Chungli, Taoyuan 320, Taiwan, ROC; Department of Chemical Engineering & Materials Science, Yuan Ze University, Chungli, Taoyuan 320, Taiwan, ROC.
⁴ Department of Neurosurgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, ROC.
⁵ Department of Pathology, Hualien Tzu Chi Hospital, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, ROC.
⁶ Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Taiwan, ROC; Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, ROC; Tzu Chi University of Science and Technology, Taiwan, ROC. Electronic address: yschen0130hth@tzuchi.com.tw.

PMID: 35158218
DOI: 10.1016/j.colsurfb.2022.112391

Abstract

Enhancement of drug efficacy is essential in cancer treatment. The immune stimulator ovalbumin (Ova)-coated citric acid (AC-)-stabilized iron oxide nanoparticles (AC-IO-Ova NPs) and enhanced permeability and retention (EPR)-based tumor targeted 4.5 generation poly(amidoamine) dendrimer(4.5GDP)-cisplatin (Cis-pt) nanocomplex (NC) (4.5GDP-Cis-pt NC) were used for enhanced anticancer efficiency. The formations of 4.5GDP-Cis-pt NC, AC-IO, and AC-IO-Ova NPs were examined via FTIR spectroscopy, X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy. The conjugation of Cis-pt with 4.5GDP was confirmed using carbon NMR spectroscopy. The tumor-specific 4.5GDP-Cis-pt NC provided 45%and 28% cumulative cisplatin release in 72 h at pH 6.5 and 7.4, respectively. A significant immune response with high TNF-α and IL-6 cytokine secretion was confirmed for the co-incubation of AC-IO-Ova with RAW 264.7 or HaCaT cells. AC-IO-Ova NPs were biocompatible with different cell lines, even at a high concentration (200 µg mL^-1). However, AC-IO-Ova NPs mixed with 4.5GDP-Cis-pt NC (Cis-pt at 15 µg mL^-1) significantly increased the cytotoxicity against the cancer cells in a dose-dependent manner with the increasing AC-IO-Ova NPs concentrations. The increased anticancer effects may be attributed to the generation of reactive oxygen species (ROS). Moreover, AC-IO-Ova NPs might assist the efficiency of anticancer cells, inducing an innate immune response via M1 macrophage polarization. We provide a novel synergistic chemoimmunotherapeutic strategy to enhance the anticancer efficacy of cisplatin via a chemotherapeutic agent 4.5GDP-Cis-pt NC and induce proinflammatory cytokines stimulating innate immunity through AC-IO-Ova NPs against tumors.

Keywords: Cisplatin release; Iron oxide; Ovalbumin; Poly(amidoamine) dendrimer; Tumour-environment targeting.

MeSH terms

Cell Survival
Cisplatin / pharmacology
Dendrimers* / pharmacology
Humans
Magnetic Iron Oxide Nanoparticles
Nanoparticles* / chemistry
Neoplasms* / therapy
Ovalbumin
Polyamines

Substances

Dendrimers
Poly(amidoamine)
Polyamines
Ovalbumin
Cisplatin