F127 poloxamer effect on cytotoxicity induction of tumour cell cultures treated with doxorubicin

Abstract

Introduction Hepatocellular carcinoma is the most common liver malignancy and the third leading cause of cancer death worldwide. One crucial limitation in the pharmacotherapy for this tumour is its chemotherapy‐resistant nature produced by the overexpression of several members of the ATP‐binding cassette protein family that efflux drugs out of cells, as observed with the breast cancer resistant protein (BCRP). Objectives This study aimed to assess the ability of Pluronic® F127 to reverse the multidrug resistance phenotype in two human hepatocellular cell lines. Methods PLC/PRF/5 and SKHep1 cells were exposed to Pluronic® F127 at several concentrations. The effect of F127 on BCRP expression (mRNA and protein), mitochondrial transmembrane potential and cell hypodiploidy was assessed. Finally, the effect of this copolymer on cytotoxicity of doxorubicin in both hepatoma cell lines was investigated, as expressed by its reverse resistance index. Key findings It was demonstrated that F127 in both cell lines contributes to chemosensitization, as shown by BCRP down‐regulation, an altered mitochondrial transmembrane potential and hypodiploidy and reverse resistance index values. A remarkable dependence of these effects significantly correlated with the copolymer concentration. Conclusions These findings further uncover the potential usefulness of this copolymer as multidrug resistance reversal agent, increasing the efficacy of cancer therapies.

Recent advances in melittin-based nanoparticles for antitumor treatment: from mechanisms to targeted delivery strategies

“…These biomimetic NPs provide good biocompatibility to prevent them from being cleared from the body via the reticuloendothelial system (RES) [93]. In addition, owing to the leaky tumor vasculature and damaged lymphatic drainage, antitumor agents can also be more selectively accumulated at tumor sites via the EPR effect in vivo [94][95][96]. Xu et al designed a library containing 82 self-assembled nanoparticles (SNPs) based on β-cyclodextrin polymers and adamantane derivatives and screened eight different types of SNPs with different charges and hydrophobic properties to suppress the toxicity of MLT to normal cells [97].…”

Doxorubicin-Loaded Polymeric Micelles Conjugated with CKR- and EVQ-FLT3 Peptides for Cytotoxicity in Leukemic Stem Cells

“…Moreover, it can directly enter cells and modulate numerous biological processes [ 33 ]. P407 and other poloxamers such as P188 were employed as a material to develop Dox-loaded nanocarriers such as hydrogel, liposome, or co-treatment with Dox for lung cancer and hepatocarcinoma therapies [ 34 , 35 , 36 ]. Due to the features of P407, it was selected to prepare the core-shell structure of polymeric micelles in this research.…”