Novel biomimetic nanosystems based on calcium orthophosphates covered by cellular membranes for bioimaging and controlled release of antineoplastics

• Grant number: 20/14417-4
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): November 01, 2022
• Effective date (End): October 31, 2024
• Field of knowledge: Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
• Principal Investigator: Valtencir Zucolotto
• Grantee: Thales Rafael Machado
• 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

Pancreatic Cancer occupies the fourth position in deaths caused by malignant neoplastic diseases and exhibits high metastasis progression rates to organs including the liver. Such facts are related to reserved prognosis for patients affected by this disease, leading to a medium survival periods of only 6 months. In modern nanomedicine, theranostic nanocarriers are in the front-line search for innovative solutions to improve the efficiency of traditional therapeutic methods, such as chemotherapy. These nanosystems allow the targeted administration of antineoplastic compounds to cancerous cells as well as the monitoring of their therapeutic effects, since the nanosystems present both diagnostic and therapeutic functions simultaneously. The present project aims to obtain novel theranostic biomimetic nanosystemas based on calcium orthophosphates (CaPs) covered with the main constituents of pancreatic and liver Cancer cell membranes. The covering procedure of CaPs nanoparticles seeks the possibility of their camouflage from the immunological system and to allow an active accumulation in target cells by homotypic self-recognition. The nanocarriers will be used to delivery gemtabicine and paclitaxel antineoplastics, which are two first line therapeutic agents often coadministered in clinics to treat distinct Cancers, including pancreatic Cancer. The pH-responsive properties of CaPs nanoparticles will be evaluated on the liberation of the drugs via dissolution of the materials into non-toxic ions due to the acidic pH of tumoral cells. It is intended to explore the real time monitoring of the nanosystems by image using the intrinsic fluorescence of CaPs, aiming the minimization of possible health risks, since potentially toxic and insoluble luminescent compounds will be avoided. This project aims to contribute with novel theranostic nanosystems inserted in a border line area of nanomedicine with potential application in image guided therapy seeking improved therapeutic and diagnostic efficiencies in tumoral cells. (AU)