3D-printing-assisted synthesis of paclitaxel-loaded niosomes functionalized by cross-linked gelatin/alginate composite: Large-scale synthesis and in-vitro anti-cancer evaluation

Fatemeh Hosseini; Masoumeh Mirzaei Chegeni; Ali Bidaki; Mohammad Zaer; Hossein Abolhassani; Seyed Arsalan Seyedi; Seyed Ali Nabipoorashrafi; Arezoo Ashrafnia Menarbazari; Alaa Moeinzadeh; Ahmad Reza Farmani; Mohammad Tavakkoli Yaraki

doi:10.1016/j.ijbiomac.2023.124697

3D-printing-assisted synthesis of paclitaxel-loaded niosomes functionalized by cross-linked gelatin/alginate composite: Large-scale synthesis and in-vitro anti-cancer evaluation

Int J Biol Macromol. 2023 Jul 1;242(Pt 1):124697. doi: 10.1016/j.ijbiomac.2023.124697. Epub 2023 May 6.

Affiliations

¹ Chemical Engineering Department, Faculty of Engineering, Ferdowsi University of Mashhad, Mashhad, Iran.
² Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
³ Biomedical Engineering Department, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran.
⁴ Department of Biomedical Engineering, University of Rochester, Rochester, NY 14627, USA.
⁵ Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran, Iran.
⁶ Department of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, Iran.
⁷ Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
⁸ Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran. Electronic address: ahmadrezafarmani66@gmail.com.
⁹ School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, NSW 2109, Australia. Electronic address: mohammad.tavakkoliyaraki@mq.edu.au.

PMID: 37156313
DOI: 10.1016/j.ijbiomac.2023.124697

Abstract

Breast cancer is one of the most lethal cancers, especially in women. Despite many efforts, side effects of anti-cancer drugs and metastasis are still the main challenges in breast cancer treatment. Recently, advanced technologies such as 3D-printing and nanotechnology have created new horizons in cancer treatment. In this work, we report an advanced drug delivery system based on 3D-printed gelatin-alginate scaffolds containing paclitaxel-loaded niosomes (Nio-PTX@GT-AL). The morphology, drug release, degradation, cellular uptake, flow cytometry, cell cytotoxicity, migration, gene expression, and caspase activity of scaffolds, and control samples (Nio-PTX, and Free-PTX) were investigated. Results demonstrated that synthesized niosomes had spherical-like, in the range of 60-80 nm with desirable cellular uptake. Nio-PTX@GT-AL and Nio-PTX had a sustained drug release and were biodegradable. Cytotoxicity studies revealed that the designed Nio-PTX@GT-AL scaffold had <5 % cytotoxicity against non-tumorigenic breast cell line (MCF-10A) but showed 80 % cytotoxicity against breast cancer cells (MCF-7), which was considerably more than the anti-cancer effects of control samples. In migration evaluation (scratch-assay), approximately 70 % reduction of covered surface area was observed. The anticancer effect of the designed nanocarrier could be attributed to gene expression regulation, where a significant increase in the expression and activity of genes promoting apoptosis (CASP-3, CASP-8, and CASP-9) and inhibiting metastasis (Bax, and p53) and a remarkable decrease in metastasis-enhancing genes (Bcl2, MMP-2, and MMP-9) were observed. Also, flow cytometry results declared that Nio-PTX@GT-AL reduced necrosis and increased apoptosis considerably. The results of this study prove that employing 3D-printing and niosomal formulation is an effective approach in designing nanocarriers for efficient drug delivery applications.

Keywords: 3D-printing; Breast cancer; Metastasis; Niosome; Paclitaxel.

MeSH terms

Alginates / therapeutic use
Breast Neoplasms* / drug therapy
Breast Neoplasms* / pathology
Cell Line, Tumor
Female
Gelatin
Humans
Liposomes / therapeutic use
MCF-7 Cells
Paclitaxel* / pharmacology
Printing, Three-Dimensional

Substances

Paclitaxel
Liposomes
Gelatin
Alginates