Eradication of cancer stem cells in triple negative breast cancer using doxorubicin/pluronic polymeric micelles.

The potency of polymeric micelle-based doxorubicin, SP1049C, against cancer stem cells (CSCs) in triple negative breast cancer (TNBC) is evaluated. CSCs with high epithelial specific antigen (ESA), high CD44 and low CD24 expression levels were derived from the TNBC cancer cells, MDA-MB-231 and MDA-MB-468. These CSCs were resistant to free doxorubicin (Dox) and displayed increased colony formation, migration, and invasion in vitro, along with higher tumorigenicity in vivo, compared to the parental and non-CSCs counterparts.

Pluronic block copolymers enhance the anti-myeloma activity of proteasome inhibitors.

Proteasome inhibitors (PIs) have markedly improved response rates as well as the survival of multiple myeloma (MM) patients over the past decade and have become an important foundation in the treatment of MM patients. Unfortunately, the majority of patients either relapses or becomes refractory to proteasome inhibition. This report describes that both PI sensitive and resistant MM cells display enhanced sensitivity to PI in the presence of synthetic amphiphilic block copolymers, Pluronics (SP1017).

Poly(2-oxazoline) based micelles with high capacity for 3rd generation taxoids: preparation, in vitro and in vivo evaluation.

The clinically and commercially successful taxanes, paclitaxel and docetaxel suffer from two major drawbacks, namely their very low aqueous solubility and the risk of developing resistance. Here, we present a method that overcomes both drawbacks in a very simple manner. We formulated 3rd generation taxoids, able to avoid common drug resistance mechanisms with doubly amphiphilic poly(2-oxazoline)s (POx), a safe and highly efficient polymer for the formulation of extremely hydrophobic drugs.

Pluronics and MDR reversal: an update.

Multidrug resistance (MDR) remains one of the biggest obstacles for effective cancer therapy. Currently there are only few methods that are available clinically that are used to bypass MDR with very limited success. In this review we describe how MDR can be overcome by a simple yet effective approach of using amphiphilic block copolymers.

Can nanomedicines kill cancer stem cells?

Most tumors are heterogeneous and many cancers contain small population of highly tumorigenic and intrinsically drug resistant cancer stem cells (CSCs). Like normal stem cell, CSCs have the ability to self-renew and differentiate to other tumor cell types. They are believed to be a source for drug resistance, tumor recurrence and metastasis.

Effect of doxorubicin/pluronic SP1049C on tumorigenicity, aggressiveness, DNA methylation and stem cell markers in murine leukemia.

Purpose: Pluronic block copolymers are potent sensitizers of multidrug resistant cancers. SP1049C, a Pluronic-based micellar formulation of doxorubicin (Dox) has completed Phase II clinical trial and demonstrated safety and efficacy in patients with advanced adenocarcinoma of the esophagus and gastroesophageal junction. This study elucidates the ability of SP1049C to deplete cancer stem cells (CSC) and decrease tumorigenicity of cancer cells in vivo.

A simple way to enhance Doxil® therapy: drug release from liposomes at the tumor site by amphiphilic block copolymer.

The antitumor efficacy of Doxil® is hindered by the poor release of the active drug from the liposome at the tumor sites. This study investigates a possibility to enhance drug release from the liposomes and increase therapeutic efficacy of Doxil® by administering Pluronic block copolymers once the liposomal drug accumulates in the tumor sites. In our study, the fluorescence de-quenching experiments were designed to investigate the drug release from liposome by Pluronic P85.

Endocytosis of nanomedicines.

Novel nanomaterials are being developed to improve diagnosis and therapy of diseases through effective delivery of drugs, biopharmaceutical molecules and imaging agents to target cells in disease sites. Such diagnostic and therapeutic nanomaterials, also termed "nanomedicines", often require site-specific cellular entry to deliver their payload to sub-cellular locations hidden beneath cell membranes. Nanomedicines can employ multiple pathways for cellular entry, which are currently insufficiently understood.

Differential metabolic responses to pluronic in MDR and non-MDR cells: a novel pathway for chemosensitization of drug resistant cancers.

A synthetic amphiphilic block copolymer, Pluronic, is a potent chemosensitizer of multidrug resistant (MDR) cancers that has shown promise in clinical trials. It has unique activities in MDR cells, which include a decrease in ATP pools and inhibition of P-glycoprotein (Pgp) resulting in increased drug accumulation in cells. This work demonstrates that Pluronic rapidly (15min) translocates into MDR cells and co-localizes with the mitochondria.

Effect of pluronic p85 on amino acid transport in bovine brain microvessel endothelial cells.

A synthetic amphiphilic block copolymer Pluronic P85 (P85) was shown to be among the most potent inhibitors of Pgp efflux system in the blood-brain barrier (BBB) and capable of enhancing delivery of Pgp substrates to the brain. The purpose of this work is to evaluate the effects of P85 on amino acid transport in BBB. Primary bovine brain microvessel endothelial cells (BBMEC) grown on membrane inserts were used as an in vitro BBB model.

Alteration of genomic responses to doxorubicin and prevention of MDR in breast cancer cells by a polymer excipient: pluronic P85.

Polymer therapeutics has emerged as a new clinical option for the treatment of human diseases. However, little is known about pharmacogenetic responses to drugs formulated with polymers. In this study, we demonstrate that a formulation containing the block copolymer Pluronic P85 and antineoplastic drug doxorubicin (Dox) prevents the development of multidrug resistance in the human breast carcinoma cell line, MCF7.