2017
DOI: 10.1002/mabi.201700186
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Codelivery for Paclitaxel and Bcl‐2 Conversion Gene by PHB‐PDMAEMA Amphiphilic Cationic Copolymer for Effective Drug Resistant Cancer Therapy

Abstract: Antiapoptotic Bcl-2 protein's upregulated expression is a key reason for drug resistance leading to failure of chemotherapy. In this report, a series of biocompatible amphiphilic cationic poly[(R)-3-hydroxybutyrate] (PHB)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) copolymer, comprising hydrophobic PHB block and cationic PDMAEMA block, is designed to codeliver hydrophobic chemotherapeutic paclitaxel and Bcl-2 converting gene Nur77/ΔDBD with enhanced stability, due to the micelle formation by hydropho… Show more

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Cited by 59 publications
(31 citation statements)
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“…2‐( N , N ‐Dimethylaminoethyl) methacrylate (DMAEMA) is a cationic pH‐responsive monomer, which is commonly incorporated into block copolymers and has been utilized in a remarkable range of applications, such as gene delivery vectors, filtration techniques, paints and coatings . Until now, the combination of poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA) and aliphatic polyesters such as poly(lactic acid), polycaprolactone and polyhydroxybutyrate has been studied with various block sequences. However, no work has been reported about PDMAEMA‐modified PBS to the best of our knowledge, although PBS is a degradable and biocompatible polyester.…”
Section: Introductionmentioning
confidence: 99%
“…2‐( N , N ‐Dimethylaminoethyl) methacrylate (DMAEMA) is a cationic pH‐responsive monomer, which is commonly incorporated into block copolymers and has been utilized in a remarkable range of applications, such as gene delivery vectors, filtration techniques, paints and coatings . Until now, the combination of poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA) and aliphatic polyesters such as poly(lactic acid), polycaprolactone and polyhydroxybutyrate has been studied with various block sequences. However, no work has been reported about PDMAEMA‐modified PBS to the best of our knowledge, although PBS is a degradable and biocompatible polyester.…”
Section: Introductionmentioning
confidence: 99%
“…[1][2][3][4] The mechanisms of MDR have been well studied, and one of the major mechanisms is the overexpression of P-glycoprotein (P-gp) in the tumor cell membrane. 5,6 P-gp, a kind of adenosine triphosphate-binding cassette transporter, is able to remove many intracellular substrates, such as paclitaxel (PTX), doxorubicin (DOX), docetaxel, vincristine and etoposide into the tumor stroma in an adenosine triphosphate-dependent manner.…”
Section: Introductionmentioning
confidence: 99%
“…Loh et al reported a naturally degradable PHB triblock cationic amphiphilic polyester that efficiently delivers the chemotherapeutic drug paclitaxel and the B-cell lymphoma-2 (Bcl-2) transgene (Nur77 gene without deoxyribonucleic acid binding domain) Nur77/ΔDBD to cancer cells via chemotherapy, and increased expression of Nur77 protein in mitochondria in cells, resulting in increased death of drug-tolerant Bcl-2/HepG2 cancer cells. [130] Soon after, Wu and his collaborators also designed an amphiphilic diblock PHB-b-poly(2-(dimethyl) methacrylate cationic polyester of aminoethyl ester) (PDMAEMA) copolymer, which can stabilize micelle formation and encapsulate hydrophobic drug by utilizing the biocompatibility, high crystallinity, biodegradability, and hydrophobicity of PHB, as shown in Figure 3. Because of PDMAEMA with positive charges, the PHB-based copolymer can co-load the chemotherapeutic drugs paclitaxel and the Bcl-2 transforming gene Nur77 to effectively overcome Bcl-2-mediated nonpump and P-glycoprotein-mediated pump-associated drug resistance.…”
Section: Drug and Gene Co-carriermentioning
confidence: 99%