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3D Porous Chitosan-Alginate Scaffolds as an In Vitro Model for Evaluating Nanoparticle-Mediated Tumor Targeting and Gene Delivery to Prostate Cancer.
Wang, Kui; Kievit, Forrest M; Florczyk, Stephen J; Stephen, Zachary R; Zhang, Miqin.
Afiliação
  • Wang K; Department of Materials Science and Engineering and ‡Department of Neurological Surgery, University of Washington , Seattle, Washington 98195, United States.
  • Kievit FM; Department of Materials Science and Engineering and ‡Department of Neurological Surgery, University of Washington , Seattle, Washington 98195, United States.
  • Florczyk SJ; Department of Materials Science and Engineering and ‡Department of Neurological Surgery, University of Washington , Seattle, Washington 98195, United States.
  • Stephen ZR; Department of Materials Science and Engineering and ‡Department of Neurological Surgery, University of Washington , Seattle, Washington 98195, United States.
  • Zhang M; Department of Materials Science and Engineering and ‡Department of Neurological Surgery, University of Washington , Seattle, Washington 98195, United States.
Biomacromolecules ; 16(10): 3362-72, 2015 Oct 12.
Article em En | MEDLINE | ID: mdl-26347946
Cationic nanoparticles (NPs) for targeted gene delivery are conventionally evaluated using 2D in vitro cultures. However, this does not translate well to corresponding in vivo studies because of the marked difference in NP behavior in the presence of the tumor microenvironment. In this study, we investigated whether prostate cancer (PCa) cells cultured in three-dimensional (3D) chitosan-alginate (CA) porous scaffolds could model cationic NP-mediated gene targeted delivery to tumors in vitro. We assessed in vitro tumor cell proliferation, formation of tumor spheroids, and expression of marker genes that promote tumor malignancy in CA scaffolds. The efficacy of NP-targeted gene delivery was evaluated in PCa cells in 2D cultures, PCa tumor spheroids grown in CA scaffolds, and PCa tumors in a mouse TRAMP-C2 flank tumor model. PCa cells cultured in CA scaffolds grew into tumor spheroids and displayed characteristics of higher malignancy as compared to those in 2D cultures. Significantly, targeted gene delivery was only observed in cells cultured in CA scaffolds, whereas cells cultured on 2D plates showed no difference in gene delivery between targeted and nontarget control NPs. In vivo NP evaluation confirmed targeted gene delivery, indicating that only CA scaffolds correctly modeled NP-mediated targeted delivery in vivo. These findings suggest that CA scaffolds serve as a better in vitro platform than 2D cultures for evaluation of NP-mediated targeted gene delivery to PCa.
Assuntos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Terapia Genética / Quitosana / Alginatos / Nanopartículas Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Biomacromolecules Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Terapia Genética / Quitosana / Alginatos / Nanopartículas Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Biomacromolecules Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos