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Cyclic-RGDfK-Directed Docetaxel Loaded Nanomicelles for Angiogenic Tumor Targeting

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Integrin Targeting Systems for Tumor Diagnosis and Therapy

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Targeting angiogenesis is a strategy to better control tumor growth and metastasis. αvβ3 is an integrin, involved in the regulation of angiogenesis and overexpressed in angiogenic endothelial cells and various cancers including breast, prostate, pancreatic, and brain cancers. cRGDfK peptide has high specificity towards αvβ3 integrin receptors. Docetaxel (DTX) is a broad spectrum anticancer drug, widely used to treat breast, ovarian, prostate, non-small-cell lung, gastric, and neck cancers. Its clinical application is limited owing to its poor aqueous solubility, low oral bioavailability, and nonspecific cytotoxicity. The nanocarriers help to overcome these limitations and further can be surface-modified to conjugate ligand to achieve selective delivery to tumor. d-α-Tocopheryl polyethylene glycol succinate (TPGS) is a water soluble derivative of natural d-α-tocopherol (Vit E). TPGS-based engineered nanocarrier systems have been shown to transport and deliver anticancer drugs more efficiently than the pristine drugs. Herein, we attempt to improve the therapeutic potential of DTX and to target the integrin receptor overexpressing angiogenic tumors, by encapsulating the DTX in nanomicelles and conjugating to cRGDfK peptide for tumor targeting. These nanomicelles are characterized by various analytical techniques and their potential of selective targeting is also evaluated. In the present chapter, we provide the general procedure used in this study: (1) synthesis and characterization of succinoyl-TPGS, (2) preparation and characterization of docetaxel loaded TPSA nanomicelles (DNM), (3) bioconjugation, quantification, and characterization of cRGDfK peptide to DNM (PDNM), (4) in vitro evaluation of cytotoxicity of the nanoparticles, (5) antiangiogenic activity, and (6) stability studies.

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Acknowledgment

H.K. and T.S. Reddy are thankful to the Director, IICT-RMIT Research Centre for providing the Junior Research Fellowships. D.P. and A.K.B. acknowledge the Council of Scientific and Industrial Research (CSIR), New Delhi and the University Grants Commission (UGC), New Delhi, respectively, for awarding Senior Research Fellowships. This work is partially supported by a CSIR grant under project Advanced Drug Delivery Systems (CSC 0302). D.J.A. is an Australian Research Council (ARC) Australian Professorial Fellow.

Declaration: The work described in this book chapter has been published as Kulhari et al., Cyclic-RGDfK peptide conjugated succinoyl-TPGS nanomicelles for targeted delivery of docetaxel to integrin receptor overexpressing angiogenic tumors. Nanomedicine. 2015;11(6):1511–1520. The work is reprinted after permission from Elsevier under license number 3671851307186.

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Authors and Affiliations

  1. IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad, India

    Hitesh Kulhari & T. Srinivasa Reddy

  2. Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500607, India

    Hitesh Kulhari, Deep Pooja, T. Srinivasa Reddy & Ramakrishna Sistla Ph.D.

  3. School of Applied Sciences, RMIT University, Melbourne, Australia

    Hitesh Kulhari

  4. Health Innovations Research Institute, RMIT University, Melbourne, Australia

    Hitesh Kulhari & David J. Adams

  5. Department of Pharmacology, National Institute of Pharmaceutical Education and Research, Hyderabad, India

    Shweta Shrivastava & V.G.M. Naidu

  6. Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Hyderabad, India

    Ayan Kumar Barui & Chitta Ranjan Patra

Authors
  1. Hitesh Kulhari
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  2. Deep Pooja
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  3. Shweta Shrivastava
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  4. T. Srinivasa Reddy
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  6. Chitta Ranjan Patra
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  7. V.G.M. Naidu
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  8. David J. Adams
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  9. Ramakrishna Sistla Ph.D.
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Corresponding author

Correspondence to Ramakrishna Sistla Ph.D. .

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Editors and Affiliations

  1. Department of Gastroenterology and Hepatology, UniversitätsSpital Zürich, Zürich, Switzerland

    Eleonora Patsenker

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Kulhari, H. et al. (2015). Cyclic-RGDfK-Directed Docetaxel Loaded Nanomicelles for Angiogenic Tumor Targeting. In: Patsenker, E. (eds) Integrin Targeting Systems for Tumor Diagnosis and Therapy. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/7653_2015_63

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  • DOI: https://doi.org/10.1007/7653_2015_63

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7443-6

  • Online ISBN: 978-1-4939-7445-0

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