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Sequential Targeting in Crosslinking Nanotheranostics for Tackling the Multibarriers of Brain Tumors.
Wu, Hao; Lu, Hongwei; Xiao, Wenwu; Yang, Jinfan; Du, Hongxu; Shen, Yingbin; Qu, Haijing; Jia, Bei; Manna, Suman K; Ramachandran, Mythili; Xue, Xiangdong; Ma, Zhao; Xu, Xiaobao; Wang, Zhongling; He, Yixuan; Lam, Kit S; Zawadzki, Robert J; Li, Yuanpei; Lin, Tzu-Yin.
Afiliação
  • Wu H; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Lu H; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Xiao W; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Yang J; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Du H; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Shen Y; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Qu H; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Jia B; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Manna SK; UC Davis RISE Eye-Pod Laboratory, Department of Cell Biology and Human Anatomy, University of California Davis, Davis, CA, 95616, USA.
  • Ramachandran M; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Xue X; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Ma Z; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Xu X; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Wang Z; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • He Y; Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Lam KS; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Zawadzki RJ; UC Davis RISE Eye-Pod Laboratory, Department of Cell Biology and Human Anatomy, University of California Davis, Davis, CA, 95616, USA.
  • Li Y; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, USA.
  • Lin TY; Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.
Adv Mater ; 32(14): e1903759, 2020 Apr.
Article em En | MEDLINE | ID: mdl-32078198
The efficacy of therapeutics for brain tumors is seriously hampered by multiple barriers to drug delivery, including severe destabilizing effects in the blood circulation, the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB), and limited tumor uptake. Here, a sequential targeting in crosslinking (STICK) nanodelivery strategy is presented to circumvent these important physiological barriers to improve drug delivery to brain tumors. STICK nanoparticles (STICK-NPs) can sequentially target BBB/BBTB and brain tumor cells with surface maltobionic acid (MA) and 4-carboxyphenylboronic acid (CBA), respectively, and simultaneously enhance nanoparticle stability with pH-responsive crosslinkages formed by MA and CBA in situ. STICK-NPs exhibit prolonged circulation time (17-fold higher area under curve) than the free agent, allowing increased opportunities to transpass the BBB/BBTB via glucose-transporter-mediated transcytosis by MA. The tumor acidic environment then triggers the transformation of the STICK-NPs into smaller nanoparticles and reveals a secondary CBA targeting moiety for deep tumor penetration and enhanced uptake in tumor cells. STICK-NPs significantly inhibit tumor growth and prolong the survival time with limited toxicity in mice with aggressive and chemoresistant diffuse intrinsic pontine glioma. This formulation tackles multiple physiological barriers on-demand with a simple and smart STICK design. Therefore, these features allow STICK-NPs to unleash the potential of brain tumor therapeutics to improve their treatment efficacy.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Portadores de Fármacos / Barreira Hematoencefálica / Nanopartículas / Antineoplásicos Limite: Animals / Humans Idioma: En Revista: Adv Mater Assunto da revista: BIOFISICA / QUIMICA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Portadores de Fármacos / Barreira Hematoencefálica / Nanopartículas / Antineoplásicos Limite: Animals / Humans Idioma: En Revista: Adv Mater Assunto da revista: BIOFISICA / QUIMICA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos