Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces journal homepage: www.elsevier.com/locate/colsurfb Increasing the effectiveness of oxaliplatin using colloidal immunoglobulin G nanoparticles: Synthesis, cytotoxicity, interaction, and release studies Mona Shahlaei, Maryam Saeidifar*, Ali Zamanian Department of Nanotechnology and Advanced Materials, Materials and Energy Research Center, Karaj, Iran ARTICLE INFO Keywords: Immunoglobulin Oxaliplatin Nanoparticle Release PCR ABSTRACT A novel biomacromolecule was prepared for a stabilizer sustained anticancer drug release system. Colloidal immunoglobulin G (IgG) nanoparticles (IgGNP) were synthesized and then characterized using FT-IR, SEM, zeta sizer, and AFM. Moreover, the formation of spherical shape IgGNP with an appropriate average size (144.56 ± 2 nm) and a narrow distribution for the drug release was confirmed. Also, the conjugation of ox- aliplatin (OX) to IgGNP (OX@IgGNP) was demonstrated via the combination of spectroscopy and physical analyses. In this regard, the interaction was spantaneous with static quenching mechanism. OX caused well dispersity with no agglomeration on IgGNP with an average size of 142.31 ± 4 nm. Furthermore, the en- capsulation efficiency (%EE) and drug loading (%DL) percentages were determined. Accordingly, the release behavior indicated that OX was sustained from IgGNP more than IgG (approximately 150 h) and the highest release amount of OX (100 %) was obtained at acidic medium (pH 5.5). Notably, the kinetic model was zero order and release mechanism followed by diffusion and Fick’s model at neutral medium and combination of diffusion and swelling controlled and non-Fickian model at acidic medium. In addition, the anticancer effect of OX@IgGNP was evaluated on the human breast cancer cell lines, MCF-7 using MTT assay and DAPI staining that showed a remarkable efficacy, while the cytotoxicity in human fibroblast cell lines, HFFF2 has decreased. In this study, gene expression was investigated using real time PCR, which verified IgGNP induced programmed cell death in MCF-7 breast cancer cell more effectively than free OX. Subsequently, a novel nano scale biological macromolecule can be introduced as a sustained and prolonged anticancer drug release. 1. Introduction The incidence of cancer is a global problem and one of the major threats to human health. There are several types of cancer treatments that depend on the type of cancer and how advanced it is. Current treatments, such as chemotherapy, radiotherapy, and immunotherapy often kill healthy cells and lead to patient toxicity [1,2]. The che- motherapeutic is often accompanied by a variety of potential side ef- fects. Platinum (II) drugs administrated as anticancer drugs, however, their significant side effects caused the strategies to improve their an- titumor properties [3–5]. Oxaliplatin (OX) is a platinum(II) compound that is used to treat lung, head, neck cervical, testicular, ovarian, and metastatic breast cancers [6]. OX is a third-generation platinum ana- logue that has been synthesized to overcome cellular resistance, more efficacies, and reduce the toxicity of previous anticancer drugs [7,8]. During the clinical trial of OX, the side effects that were often mentioned hematological toxicity, gastrointestinal tract toxicity, and peripheral neuropathy which were unlike other platinum drugs [9]. In addition, advances in protein engineering and materials science have helped in a new way to the target, which may give cancer patients new hope. Several nanoparticles have been approved for administration and have been suggested by providing different mechanisms for a unique strategy to achieve increased cancer treatment [1,10]. Polymers including polysaccharides and proteins can conjugate to platinum (II) central atoms by their amino groups and increase the stability of platinum (II) complex [6,11]. The most desirable ligands for binding to platinum (II) are the polymers containing carboxyl and hy- droxyl groups [12,13]. In the bloodstream, the Oxalate ligand of OX binds rapidly with sulfur groups of small biomolecules such as glu- tathione, cysteine, and methionine, and then with plasma proteins, al- bumin, and IgG [10]. According to the past research, the proteins with M W (60-200 kDa) just like albumin (60 kDa) and immunoglobulin G (IgG, 150-160 kDa) can be contained each 40 % of the platinum bound [14,15]. Immunoglobulin G (IgG) is gamma globulins that widely used in immunoassay in cancer patients, protein-specific glycosylation in cancer and biochemical analyses. IgG molecules tend to interact with https://doi.org/10.1016/j.colsurfb.2020.111255 Received 9 March 2020; Received in revised form 13 June 2020; Accepted 10 July 2020 ⁎ Corresponding author. E-mail address: saeidifar@merc.ac.ir (M. Saeidifar). Colloids and Surfaces B: Biointerfaces 195 (2020) 111255 Available online 13 July 2020 0927-7765/ © 2020 Published by Elsevier B.V. T