Cyclic-RGDfK-directed docetaxel loaded nanomicelles for angiogenic tumor targeting

Kulhari, H, Kulhari, D, Shrivastava, S, Telukutla, S, Barui, A, Patra, C, Naidu, V, Adams, D and Sistla, R 2018, 'Cyclic-RGDfK-directed docetaxel loaded nanomicelles for angiogenic tumor targeting', Methods in Pharmacology and Toxicology, pp. 157-168.


Document type: Journal Article
Collection: Journal Articles

Title Cyclic-RGDfK-directed docetaxel loaded nanomicelles for angiogenic tumor targeting
Author(s) Kulhari, H
Kulhari, D
Shrivastava, S
Telukutla, S
Barui, A
Patra, C
Naidu, V
Adams, D
Sistla, R
Year 2018
Journal name Methods in Pharmacology and Toxicology
Start page 157
End page 168
Total pages 12
Publisher Humana Press, Inc.
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.
Subject Nanobiotechnology
Nanomedicine
Keyword(s) Nanomicelles
Docetaxel
Angiogenesis
TPGS
Bioconjugation
Targeted delivery
Cancer therapy
DOI - identifier 10.1007/7653_2015_63
Copyright notice © Springer Science+Business Media New York 2015
ISSN 1557-2153
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