Carcinoembryonic antigen-targeted nanoparticles potentiate the delivery of anticancer drugs to colorectal cancer cells

被引:24
|
作者
Pereira, Ines [1 ,2 ,3 ]
Sousa, Flavia [1 ,2 ,4 ,5 ,7 ]
Kennedy, Patrick [1 ,2 ,6 ,7 ]
Sarmento, Bruno [1 ,2 ,4 ,5 ,8 ]
机构
[1] Univ Porto, Inst Invest & Inovacao Saude I3S, Rua Alfredo Allen 208, P-4200135 Porto, Portugal
[2] Univ Porto, INEB Inst Engn Biomed, Rua Alfredo Allen 208, P-4200135 Porto, Portugal
[3] Univ Porto, FEUP Fac Engn, Rua Dr Roberto Frias, P-4200465 Porto, Portugal
[4] CESPU Inst Invest & Formacao Avancada Ciencias &, Rua Cent Gandra 1317, Gandra, Portugal
[5] Inst Univ Ciencias Saude, Rua Cent Gandra 1317, Gandra, Portugal
[6] Univ Porto, IPATIMUP Inst Patol & Imunol Mol, Rua Julio Amaral de Carvalho 45, P-4200135 Porto, Portugal
[7] Univ Porto, ICBAS Inst Ciencias Biomed Abel Salazar, Rua Jorge de Viterbo Ferreira 228, P-4050313 Porto, Portugal
[8] Queens Univ Belfast, Sch Pharm, Med Biol Ctr, Belfast, Antrim, North Ireland
关键词
Drug delivery; Carcinoembryonic antigen; Targeted nanoparticles; Colorectal cancer; PLGA-BASED NANOPARTICLES; IN-VITRO; PACLITAXEL; THERAPY; ABSORPTION; PEGYLATION; ANTIBODIES; MICELLES;
D O I
10.1016/j.ijpharm.2018.08.016
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Bioengineered functionalized nanoparticles have extensively been proposed in recent years to efficiently deliver anti-cancer drugs to the tumour site, by targeting the cancer cells and improving the therapeutic efficiency of active molecules. In this work, polymeric poly (lactic-co- glycolic)-polyethyleneglycol (PLGA-PEG) nanoparticles were produced by nanoprecipitation and loaded with paclitaxel, following surface-functionalized with a monoclonal antibody targeting the carcinoembryonic antigen (CEA) of intestinal epithelial cells. Physicochemical properties, cytotoxicity and targeting ability of the nanoparticles against two intestine epithelial carcinoma cell lines, CEA-expressing Caco-2 clone and non-CEA-expressing SW480, were assessed. Results showed successful production of nanoparticles around 200 nm, and close to charge neutrality, encapsulating up to 99% of paclitaxel. Functionalized nanoparticles were further constructed, demonstrating to be non-cytotoxic against intestinal cells. The targeting ability of functionalized nanoparticles to Caco-2 CEA expressing cells was confirmed by flow cytometry, in opposite to SW480 cells. Overall, the surface-modified PLGA-PEG nanoparticles with the CEA-targeting antibody were successfully developed as nanocarriers for paclitaxel and interacted with CEA expressing cells. This specific interaction provide these particles ability to be used as targeted systems for colorectal cancer therapeutics.
引用
收藏
页码:397 / 403
页数:7
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