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Calcium phosphate nanoparticles chemically modified with targeting components using click chemistry for the delivery of anticancer drugs

Grant number: 23/12673-1
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): March 01, 2024
Effective date (End): February 28, 2025
Field of knowledge:Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
Principal Investigator:Valtencir Zucolotto
Grantee:Thales Rafael Machado
Supervisor: Matthias Epple
Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
Research place: University of Duisburg-Essen, Essen, Germany  
Associated to the scholarship:20/14417-4 - Novel biomimetic nanosystems based on calcium orthophosphates covered by cellular membranes for bioimaging and controlled release of antineoplastics, BP.PD

Abstract

The use of nanocarriers for drug delivery has attracted significant attention for its potential to overcome limitations associated with conventional treatment methods, especially in cancer therapy. Among various nanoparticles (NPs) investigated for this purpose, calcium phosphate (CaP) NPs have emerged as highly promising nanocarriers due to their outstanding biocompatibility, biodegradability, pH-responsive behavior, efficient loading of bioactive substances, and cost-effective synthesis methods. The CaP NPs can encapsulate therapeutic payloads, enhancing protection against degradation until they reach specific target areas within physiological systems. Furthermore, the versatile surface chemistry of CaP NPs allows the functionalization with stabilizing agents and targeting molecules. However, due to the ionic nature of CaPs, the functionalization of NPs with bioactive molecules through covalent bonding is challenging. This proposal aims the use of novel CaP NPs covalently modified with targeting molecules for the delivery of antineoplastic agents. The CaP core will be synthesized through chemical precipitation in the presence of gemcitabine (GEM) as a model drug and polyethyleneimine (PEI) to enhance the colloidal stability of the NPs. A thin SiO2 shell will be added to enable subsequent covalent bonding. Folic acid (FA) will serve as the targeting moiety for cancer cells that overexpress folate receptors. The attachment will be achieved through a click reaction involving a copper-catalyzed azide-alkyne cycloaddition (CuAAC). We hypothesize that the CaP/PEI/SiO2 platform is promising for achieving high loading efficiency of GEM and robust functionalization with FA, enabling selective drug delivery. (AU)

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