Fluorescent nanocarriers based on amorphous calcium phosphate nanoparticles for the controlled release of Gemcitabine

• Grant number: 21/11424-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2021
• Effective date (End): May 31, 2022
• Field of knowledge: Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
• Principal Investigator: Valtencir Zucolotto
• Grantee: Lucas Trindade Pereira
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 14/50947-7 - INCT 2014: in Stem Cell and Cell Therapy, AP.TEM

Abstract

Most cancer drugs are water-insoluble, untargeted, and have high side effects. In order to overcome these limitations, the development of carrier systems based on biocompatible nanoparticles (NPs) for the intracellular delivery of bioactive drugs has attracted attention in modern nanomedicine. Nanocarriers composed of calcium phosphates (CaPs) stand out due to their unique properties, such as high biocompatibility, adjustable biodegradability, easy preparation, and functionalization, as well as their significant capacity to carry different antineoplastic agents, genes, and proteins. Furthermore, the NPs of CaPs have structures capable of accepting several ionic substitutions, generating new properties useful in diagnosis, which allow them to act as theranostic platforms in the concomitant controlled and monitored release of bioactive molecules. This project aims to evaluate the loading and controlled release capacity of the antineoplastic agent gemcitabine, a first-line therapeutic agent used in clinical practice in the treatment of pancreatic cancer, using amorphous calcium phosphate carbonate NPS as a nanocarrier vehicle. We intend to verify the simultaneous release of Ca2+ ions by the pH-responsive dissolution of NPs, a reaction pointed out as potentiating apoptosis in cancer cells and, as a consequence, in the therapeutic effectiveness of the nanoparticulate system. The possibility of monitoring these processes through intrinsic luminescence of NPs, without the presence of activating ions or other luminescent compounds, will be evaluated for future uses in image-guided therapy. (AU)