Tags

Type your tag names separated by a space and hit enter

Co-delivery of siRNA and paclitaxel into cancer cells by biodegradable cationic micelles based on PDMAEMA-PCL-PDMAEMA triblock copolymers.
Biomaterials 2010; 31(8):2408-16B

Abstract

Biodegradable cationic micelles were prepared from PDMAEMA-PCL-PDMAEMA triblock copolymers and applied for the delivery of siRNA and paclitaxel into cancer cells. PDMAEMA-PCL-PDMAEMA copolymers were readily obtained by reversible addition-fragmentation chain transfer (RAFT) polymerization of dimethylaminoethyl methacrylate (DMAEMA) using CPADN-PCL-CPADN (CPADN: 4-cyanopentanoic acid dithionaphthalenoate; PCL: 3600 Da) as a macro-RAFT agent. The molecular weights of PDMAEMA blocks, controlled by monomer/CPADN-PCL-CPADN mole ratios, varied from 2700, 4800 to 9100 (denoted as polymer 1, 2 and 3, respectively). These triblock copolymers formed nano-sized micelles in water with positive surface charges ranging from +29.3 to +35.5 mV. Both micelles 1 and 2 revealed a low cytotoxicity. Gel retardation assay showed that micelles 1 and 2 could effectively complex with siRNA at and above N/P ratios of 4/1 and 2/1, respectively. Notably, GFP siRNA complexed with micelle 1 exhibited significantly enhanced gene silencing efficiency as compared to that formulated with 20 kDa PDMAEMA or 25kDa branched PEI in GFP-expressed MDA-MB-435-GFP cells. Moreover, micelle 1 loaded with paclitaxel displayed higher drug efficacy than free paclitaxel in PC3 cells, due to most likely improved cellular uptake. The combinatorial delivery of VEGF siRNA and paclitaxel showed an efficient knockdown of VEGF expression. Confocal laser scanning microscope studies on GFP siRNA complexed with nile red-loaded micelle revealed that nile red was delivered into GFP-expressed MDA-MB-435-GFP cells and that GFP expression was significantly inhibited. These results demonstrated that cationic biodegradable micelles are highly promising for the combinatorial delivery of siRNA and lipophilic anti-cancer drugs.

Authors+Show Affiliations

Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19963269

Citation

Zhu, Caihong, et al. "Co-delivery of siRNA and Paclitaxel Into Cancer Cells By Biodegradable Cationic Micelles Based On PDMAEMA-PCL-PDMAEMA Triblock Copolymers." Biomaterials, vol. 31, no. 8, 2010, pp. 2408-16.
Zhu C, Jung S, Luo S, et al. Co-delivery of siRNA and paclitaxel into cancer cells by biodegradable cationic micelles based on PDMAEMA-PCL-PDMAEMA triblock copolymers. Biomaterials. 2010;31(8):2408-16.
Zhu, C., Jung, S., Luo, S., Meng, F., Zhu, X., Park, T. G., & Zhong, Z. (2010). Co-delivery of siRNA and paclitaxel into cancer cells by biodegradable cationic micelles based on PDMAEMA-PCL-PDMAEMA triblock copolymers. Biomaterials, 31(8), pp. 2408-16. doi:10.1016/j.biomaterials.2009.11.077.
Zhu C, et al. Co-delivery of siRNA and Paclitaxel Into Cancer Cells By Biodegradable Cationic Micelles Based On PDMAEMA-PCL-PDMAEMA Triblock Copolymers. Biomaterials. 2010;31(8):2408-16. PubMed PMID: 19963269.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Co-delivery of siRNA and paclitaxel into cancer cells by biodegradable cationic micelles based on PDMAEMA-PCL-PDMAEMA triblock copolymers. AU - Zhu,Caihong, AU - Jung,Sooyeon, AU - Luo,Sibin, AU - Meng,Fenghua, AU - Zhu,Xiulin, AU - Park,Tae Gwan, AU - Zhong,Zhiyuan, Y1 - 2009/12/05/ PY - 2009/10/21/received PY - 2009/11/23/accepted PY - 2009/12/8/entrez PY - 2009/12/8/pubmed PY - 2010/4/17/medline SP - 2408 EP - 16 JF - Biomaterials JO - Biomaterials VL - 31 IS - 8 N2 - Biodegradable cationic micelles were prepared from PDMAEMA-PCL-PDMAEMA triblock copolymers and applied for the delivery of siRNA and paclitaxel into cancer cells. PDMAEMA-PCL-PDMAEMA copolymers were readily obtained by reversible addition-fragmentation chain transfer (RAFT) polymerization of dimethylaminoethyl methacrylate (DMAEMA) using CPADN-PCL-CPADN (CPADN: 4-cyanopentanoic acid dithionaphthalenoate; PCL: 3600 Da) as a macro-RAFT agent. The molecular weights of PDMAEMA blocks, controlled by monomer/CPADN-PCL-CPADN mole ratios, varied from 2700, 4800 to 9100 (denoted as polymer 1, 2 and 3, respectively). These triblock copolymers formed nano-sized micelles in water with positive surface charges ranging from +29.3 to +35.5 mV. Both micelles 1 and 2 revealed a low cytotoxicity. Gel retardation assay showed that micelles 1 and 2 could effectively complex with siRNA at and above N/P ratios of 4/1 and 2/1, respectively. Notably, GFP siRNA complexed with micelle 1 exhibited significantly enhanced gene silencing efficiency as compared to that formulated with 20 kDa PDMAEMA or 25kDa branched PEI in GFP-expressed MDA-MB-435-GFP cells. Moreover, micelle 1 loaded with paclitaxel displayed higher drug efficacy than free paclitaxel in PC3 cells, due to most likely improved cellular uptake. The combinatorial delivery of VEGF siRNA and paclitaxel showed an efficient knockdown of VEGF expression. Confocal laser scanning microscope studies on GFP siRNA complexed with nile red-loaded micelle revealed that nile red was delivered into GFP-expressed MDA-MB-435-GFP cells and that GFP expression was significantly inhibited. These results demonstrated that cationic biodegradable micelles are highly promising for the combinatorial delivery of siRNA and lipophilic anti-cancer drugs. SN - 1878-5905 UR - https://www.unboundmedicine.com/medline/citation/19963269/Co_delivery_of_siRNA_and_paclitaxel_into_cancer_cells_by_biodegradable_cationic_micelles_based_on_PDMAEMA_PCL_PDMAEMA_triblock_copolymers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0142-9612(09)01321-0 DB - PRIME DP - Unbound Medicine ER -