Enhancement of chlorpromazine antitumor activity by Pluronics F127/L81 nanostructured system against human multidrug resistant leukemia.
The development of specific tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia (CML). However, chemoresistance of tumor cells to TKIs has already been described, and several mechanisms account for the multidrug resistance (MDR) phenotypes, including the overexpression of P-glycoprotein (P-gp). This decreases the rate of healing and complete tumor remission. Nanotechnological tools have been studied to allow advances in this field. Poloxamers (Pluronics(®)) have been proposed as drug carriers to improve therapeutic efficacy and decrease side effects, even in cancer therapy, due to their ability to inhibit P-gp. Antipsychotic phenothiazines have been described as potent cytotoxic drugs against several types of tumor cells in vitro. Here, we show that nanostructured micellar systems containing the phenothiazine derivative chlorpromazine (CPZ) potentiated the cytotoxicity of free CPZ and increased the selectivity against CML tumor cells, demonstrating the pharmacological potential of these poloxamer-based nanostructured systems containing CPZ in cancer therapy.
Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), Santo André, SP, Brazil.
Joyce C de
JC
Mello
Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), Santo André, SP, Brazil.
Vivian Wr
VW
Moraes
Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), Santo André, SP, Brazil.
Carolina M
CM
Watashi
Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), Santo André, SP, Brazil.
Deyse C
DC
da Silva
Faculdade de Engenharia Quimica, Universidade de Campinas (Unicamp), Campinas, SP, Brazil.
Leide P
LP
Cavalcanti
Instituto de Pesquisas Energéticas e Nucleares (IPEN), São Paulo, SP, Brazil.
Margareth Kkd
MK
Franco
Department Quantum Phenomena in Novel Materials, Helmholtz-Zentrum Berlin für Materialien und Energie GmbH, Hahn-Meitner-Platz 1, Berlin, Germany.
Fabiano
F
Yokaichiya
Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), Santo André, SP, Brazil.
Daniele R
DR
de Araujo
Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), Santo André, SP, Brazil. Electronic address: tiago.rodrigues@ufabc.edu.br.
Tiago
T
Rodrigues
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002746:Chlorpromazine / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008823:Micelles; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles; D020442:Poloxamer / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D013997:Time Factors
D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D020442:Poloxamer; D002746:Chlorpromazine
Cancer therapy; Leukemia; Multidrug resistance; Nanostructured systems; Phenothiazines; Poloxamers