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Multifunctional nanoparticles for SITE-ESPECIFIC delivery of temozolomide and verteporfin for combination therapy of brain tumors

Grant number: 16/00389-3
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): September 01, 2016
Effective date (End): May 31, 2017
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Antonio Claudio Tedesco
Grantee:Diogo Silva Pellosi
Home Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Glioblastoma multiform are one of the most aggressive and mortal human cancers. The most used chemotherapeutic drug for its treatment is Temozolomide (TMZ); however, the blood brain barrier significantly limits its efficacy. A nanostructured material that present the extraordinary characteristic to overcome the blood brain barrier are the micelles based on Pluronic surfactants. In a previous work, we have demonstrated that Pluronic P123/F127 mixed micelles are able to load and stabilize the very hydrophobic drug Verteporfin for visible light therapy application. TMZ have been successfully combined with phototherapies showing synergistic anticancer activity, however clinical trials are still distant due blood brain barrier inhibitory action. Therefore, encapsulate both drugs into Pluronic nanoparticles, especially developed for glioma treatment, is a promising strategy. In addition Pluronic can be synthetically modified in order to insert different functional molecules on its structure as fluorescent probes to tumor imaging and/or targeting agents to increase tumor selectivity. Thus, the aims of the present project are: (i) to develop a multifunctional nanostructured system for TMZ and Verteporfin loading; (ii) optimize the formulation and stability properties of the developed nanoparticle and (iii) demonstrate a significant increase of glioma anticancer activity due the synergistic association of multifunctional nanoparticles and chemo-photodynamic combined therapy.

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)
SOUZA, CARLA; PELLOSI, DIOGO SILVA; TEDESCO, ANTONIO CLAUDIO. Prodrugs for targeted cancer therapy. EXPERT REVIEW OF ANTICANCER THERAPY, v. 19, n. 6, p. 483-502, JUN 3 2019. Web of Science Citations: 0.
PELLOSI, DIOGO S.; PAULA, LEONARDO B.; DE MELO, MARYANNE T.; TEDESCO, ANTONIO C. Targeted and Synergic Glioblastoma Treatment: Multifunctional Nanoparticles Delivering Verteporfin as Adjuvant Therapy for Temozolomide Chemotherapy. MOLECULAR PHARMACEUTICS, v. 16, n. 3, p. 1009-1024, MAR 2019. Web of Science Citations: 2.
PELLOSI, DIOGO SILVA; MACAROFF, PATRICIA PEREIRA; MORAIS, PAULO CESAR; TEDESCO, ANTONIO CLAUDIO. Magneto low-density nanoemulsion (MLDE): A potential vehicle for combined hyperthermia and photodynamic therapy to treat cancer selectively. Materials Science & Engineering C-Materials for Biological Applications, v. 92, p. 103-111, NOV 1 2018. Web of Science Citations: 4.
DAVANZO, NATHALIA NOSSI; PELLOSI, DIOGO SILVA; FRANCHI, LEONARDO PEREIRA; TEDESCO, ANTONIO CLAUDIO. Light source is critical to induce glioblastoma cell death by photodynamic therapy using chloro-aluminiumphtalocyanine albumin-based nanoparticles. Photodiagnosis and Photodynamic Therapy, v. 19, p. 181-183, SEP 2017. Web of Science Citations: 6.
PELLOSI, DIOGO SILVA; CALORI, ITALO RODRIGO; DE PAULA, LEONARDO BARCELOS; HIOKA, NOBORU; QUAGLIA, FABIANA; TEDESCO, ANTONIO CLAUDIO. Multifunctional theranostic Pluronic mixed micelles improve targeted photoactivity of Verteporfin in cancer cells. Materials Science & Engineering C-Materials for Biological Applications, v. 71, p. 1-9, FEB 1 2017. Web of Science Citations: 15.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.