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Study of lipid-based nanoparticles as carriers for anticancer ruthenium metallodrugs

Grant number: 14/23481-7
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): October 01, 2015
Effective date (End): August 31, 2019
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal Investigator:Denise de Oliveira Silva
Grantee:Samara Rodrigues Alves
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):15/24252-4 - Study of lipid based nanoparticles as carriers for anticancer ruthenium metallodrugs, BE.EP.DD


Ruthenium compounds have received great attention in the field of metallodrugs because of their potential as anticancer agents. Complexes containing Ru2(II,III) dimetal cores coordinated to Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) developed in our research group have shown promising results in studies in vitro and in vivo in glioma models, such as the glioblastoma multiforme, a highly malignant brain cancer. The main objectives of this project are to study the interactions of Ru2(II,III)-NSAID complexes with aminopyridines and to investigate the feasibility of developing hybrid nanoparticle systems that can promote loading and sustained release of the metallodrugs. Lipid nanoparticles are capable of crossing the blood brain barrier and are promising for the treatment of gliomas, allowing, among other things, to increase the intracellular and intratumoral bioavailability and to lower the systemic toxicity of antitumor drugs. The main goals of the research plan are: 1) to prepare ruthenium-NSAID complexes, in particular NSAID = ibuprofen, and to investigate their interaction with 4-aminopyridine to try to prepare new mixed derivatives; 2) to perform tests of partition of the studied complexes in some saturated and unsaturated lipids to select the most appropriate lipids; 3) to develop methodology for preparation of lipid nanoparticles containing the metallodrugs; 4) to characterize the complexes and the materials obtained by means of several techniques; 5) to investigate the feasibility of releasing the metallodrugs from the hybrid materials; 6) to establish collaborations to conduct studies in vitro and/or in vivo in order to verify the potential application of the systems in anticancer treatments. (AU)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MARCIO HAYASHI; SAMARA R. ALVES; IGUATINÃ M. COSTA; DENISE DE OLIVEIRA SILVA. Self-Assembled Nanoparticles of Diruthenium(II,III)-Ibuprofen Anticancer Metallodrug. Journal of the Brazilian Chemical Society, v. 31, n. 11, p. 2331-2341, . (16/23028-6, 14/23047-5, 14/23481-7)
REHMAN, HANIF-UR-; FORNACIARI, BARBARA; ALVES, SAMARA R.; COLQUHOUN, ALISON; SILVA, DENISE DE OLIVEIRA. Diruthenium(II-III)-ibuprofen-loaded chitosan-based microparticles and nanoparticles systems: encapsulation, characterisation, anticancer activity of the nanoformulations against U87MG human glioma cells. Journal of Microencapsulation, v. 40, n. 7, p. 17-pg., . (14/23047-5, 14/23481-7)
ALVES RICO, SAMARA R.; ABBASI, AZHAR Z.; RIBEIRO, GEISE; AHMED, TAKSIM; WU, XIAO YU; SILVA, DENISE DE OLIVEIRA. Diruthenium(II,III) metallodrugs of ibuprofen and naproxen encapsulated in intravenously injectable polymer-lipid nanoparticles exhibit enhanced activity against breast and prostate cancer cells. NANOSCALE, v. 9, n. 30, p. 10701-10714, . (14/23047-5, 14/23481-7, 15/24252-4, 11/06592-1)
ALVES, SAMARA R.; SANTOS, RODRIGO L. S. R.; FORNACIARI, BARBARA; COLQUHOUN, ALISON; SILVA, DENISE DE OLIVEIRA. A novel mu-oxo-diruthenium(III,III)-ibuprofen-(4-aminopyridine) chloride derived from the diruthenium(II,III)-ibuprofen paddlewheel metallodrug shows anticancer properties. Journal of Inorganic Biochemistry, v. 225, . (14/23481-7, 14/23047-5)
ALVES, SAMARA RODRIGUES; COLQUHOUN, ALISON; WU, XIAO YU; SILVA, DENISE DE OLIVEIRA. Synthesis of terpolymer-lipid encapsulated diruthenium(II,III)-anti-inflammatory metallodrug nanoparticles to enhance activity against glioblastoma cancer cells. Journal of Inorganic Biochemistry, v. 205, . (14/23481-7, 15/24252-4, 14/23047-5)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
ALVES, Samara Rodrigues. Nanoencapsulation of dirutenium (II, III) antitumor metallodrugs containing ibuprofen and naproxen. Study of a novel µ-oxo-ruthenium(III)-ibuprofen-4-aminopyridine metallodrug. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.

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