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Bifunctional Elastin-like Polypeptide Nanoparticles Bind Rapamycin and Integrins and Suppress Tumor Growth in Vivo.
Dhandhukia, Jugal P; Shi, Pu; Peddi, Santosh; Li, Zhe; Aluri, Suhaas; Ju, Yaping; Brill, Dab; Wang, Wan; Janib, Siti M; Lin, Yi-An; Liu, Shuanglong; Cui, Honggang; MacKay, J Andrew.
Afiliación
  • Dhandhukia JP; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California School of Pharmacy , Los Angeles, California 90089, United States.
  • Shi P; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California School of Pharmacy , Los Angeles, California 90089, United States.
  • Peddi S; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California School of Pharmacy , Los Angeles, California 90089, United States.
  • Li Z; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California School of Pharmacy , Los Angeles, California 90089, United States.
  • Aluri S; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California School of Pharmacy , Los Angeles, California 90089, United States.
  • Ju Y; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California School of Pharmacy , Los Angeles, California 90089, United States.
  • Brill D; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California School of Pharmacy , Los Angeles, California 90089, United States.
  • Wang W; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California School of Pharmacy , Los Angeles, California 90089, United States.
  • Janib SM; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California School of Pharmacy , Los Angeles, California 90089, United States.
  • Lin YA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University , Baltimore, Maryland 21218, United States.
  • Cui H; Department of Chemical and Biomolecular Engineering, Johns Hopkins University , Baltimore, Maryland 21218, United States.
  • MacKay JA; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California School of Pharmacy , Los Angeles, California 90089, United States.
Bioconjug Chem ; 28(11): 2715-2728, 2017 11 15.
Article en En | MEDLINE | ID: mdl-28937754
Recombinant protein-polymer scaffolds such as elastin-like polypeptides (ELPs) offer drug-delivery opportunities including biocompatibility, monodispersity, and multifunctionality. We recently reported that the fusion of FK-506 binding protein 12 (FKBP) to an ELP nanoparticle (FSI) increases rapamycin (Rapa) solubility, suppresses tumor growth in breast cancer xenografts, and reduces side effects observed with free-drug controls. This new report significantly advances this carrier strategy by demonstrating the coassembly of two different ELP diblock copolymers containing drug-loading and tumor-targeting domains. A new ELP nanoparticle (ISR) was synthesized that includes the canonical integrin-targeting ligand (Arg-Gly-Asp, RGD). FSI and ISR mixed in a 1:1 molar ratio coassemble into bifunctional nanoparticles containing both the FKBP domain for Rapa loading and the RGD ligand for integrin binding. Coassembled nanoparticles were evaluated for bifunctionality by performing in vitro cell-binding and drug-retention assays and in vivo MDA-MB-468 breast tumor regression and tumor-accumulation studies. The bifunctional nanoparticle demonstrated superior cell target binding and similar drug retention to FSI; however, it enhanced the formulation potency, such that tumor growth was suppressed at a 3-fold lower dose compared to an untargeted FSI-Rapa control. This data suggests that ELP-mediated scaffolds are useful tools for generating multifunctional nanomedicines with potential activity in cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Portadores de Fármacos / Integrinas / Elastina / Sirolimus / Antibióticos Antineoplásicos Límite: Animals / Female / Humans Idioma: En Revista: Bioconjug Chem Asunto de la revista: BIOQUIMICA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Portadores de Fármacos / Integrinas / Elastina / Sirolimus / Antibióticos Antineoplásicos Límite: Animals / Female / Humans Idioma: En Revista: Bioconjug Chem Asunto de la revista: BIOQUIMICA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos