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Synthesis and characterization of chitosan-boronate nanoparticles containing quercetin for use in cancer therapy

Grant number: 19/12352-5
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2019
Effective date (End): July 09, 2020
Field of knowledge:Interdisciplinary Subjects
Principal Investigator:Rose Mary Zumstein Georgetto Naal
Grantee:Carolina Maria Monge
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Cancer is currently one of the global death leaders, with an estimated 13 million deaths by the year 2030. Oxidative stress has been pointed out as one of the causes of cancer, since the imbalance between the production of reactive oxygen species (ROS) and its elimination from the organism can lead to cellular damage with potential carcinogenesis. Cells of the immune system, such as mast cells and leukocytes, release large amounts of ROS to defend against acute inflammatory processes. When the inflammation persists, and becomes chronic, there is an imbalance of the ROS favoring oxidative stress and cancer. In this context, it is evident that antioxidants accessible to cell signaling mechanisms offer good prospects for the prevention and treatment of cancer by strengthening the immune system. Several natural antioxidants have been identified with the ability to interfere in the redox signaling mechanisms and in the diseases resulting from the ROS imbalance. Among them, polyphenolic compounds may be cited, such as quercetin, for which the antiproliferative, antiangiogenic and apoptotic effects have been reported. Despite the unquestionable applicability of natural antioxidants, they have low bioavailability and considerable chemical instability that compromise therapeutic efficacy. In this context, this work proposes the study of polymeric nanoparticles (NPs) of chitosan, which will be chemically modified with phenylboronic acid (AFB), known to be easily bonded with diols forming the boronate ester, which exhibits rapid response to the acidic pH of the means. At physiological pH this binding is stable, while at acidic pH (tumor site) the dissociation of this binding occurs, disrupting the NP and releasing the active molecules in the cellular medium. The characterization of the synthesized polymer will be done based on the chemical structure, concentration of critical aggregation and degree of polymer substitution. Polymeric NPs will be characterized in terms of size, polydispersity, zeta potential, morphology, in vitro release and cellular uptake. The in vitro anti-cancer potential of the free or nanoparticulate polyphenol will be driven by MTT assay in breast cancer cell line (MCF-7). The in vitro allergenic potential of the nanoparticles will be evaluated through antigen-induced mast cell degranulation (NAAL et al., 2004). It is hoped that this study will contribute to the development of nanoformulations containing natural compounds applicable in cancer therapy. The success of this study opens perspectives of synergistic evaluation between polyphenols and conventional anticancer drugs.

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