Nanobody-albumin nanoparticles (NANAPs) for the delivery of a multikinase inhibitor 17864 to EGFR overexpressing tumor cells.
ABSTRACT A novel, EGFR-targeted nanomedicine has been developed in the current study. Glutaraldehyde crosslinked albumin nanoparticles with a size of approximately 100nm were loaded with the multikinase inhibitor 17864-L(x) -a platinum-bound sunitinib analogue- which couples the drug to methionine residues of albumin and is released in a reductive environment. Albumin nanoparticles were surface-coated with bifunctional polyethylenglycol 3500 (PEG) and a nanobody -the single variable domain of an antibody- (Ega1) against the epidermal growth factor receptor (EGFR). EGa1-PEG functionalized nanoparticles showed a 40-fold higher binding to EGFR-positive 14C squamous head and neck cancer cells in comparison to PEGylated nanoparticles. 17864-L(x) loaded EGa1-PEG nanoparticles were internalized by clathrin-mediated endocytosis and ultimately digested in lysosomes. The intracellular routing of EGa1 targeted nanoparticles lead to successful release of the kinase inhibitor in the cell and inhibition of proliferation whereas the non-targeted formulations had no antiproliferative effects on 14C cells. The drug loaded targeted nanoparticles were as effective as the free drug in vitro. These results demonstrate that multikinase inhibitor loaded nanoparticles are interesting nanomedicines for the treatment of EGFR-positive cancers.
Full-textDOI: · Available from: Maryam Amidi, May 30, 2015
SourceAvailable from: Hasan KouchakzadehAdvances in Protein Chemistry and Structural Biology, 03/2015: chapter 4: pages 121-143; Elsevier., ISBN: 1876-1623
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ABSTRACT: Head-and-neck cancer is a major form of the disease worldwide. Treatment consists of surgery, radiation therapy and chemotherapy, but these have not resulted in improved survival rates over the past few decades. Versatile nanoparticles, with selective tumor targeting, are considered to have the potential to improve these poor outcomes. Application of nanoparticle-based targeted therapeutics has extended into many areas, including gene silencing, chemotherapeutic drug delivery, radiosensitization, photothermal therapy, and has shown much promise. In this review, we discuss recent advances in the field of nanoparticle-mediated targeted therapeutics for head-and-neck cancer, with an emphasis on the description of targeting points, including future perspectives.International journal of medical sciences 01/2015; 12(2):187-200. DOI:10.7150/ijms.10083 · 1.55 Impact Factor
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ABSTRACT: Albumin nanoparticles are one of the most important drug carriers for the delivery of therapeutic drugs, especially for the treatment of malignancies. This potential is due to their high binding capacity for both hydrophobic and hydrophilic drugs and the possibility of surface modification. Accumulation of albumin-bound drugs in the tumor interstitium occurs by the enhanced permeability and retention effect, which is also facilitated by the 60-kDa glycoprotein transcytosis pathway and binding to secreted protein, acidic and rich in cysteine located in the tumor extracellular matrix. In addition, specific ligands such as monoclonal antibodies, folic acid, transferrin, and peptides can be conjugated to the surface of albumin nanoparticles to actively target the drug to its site of action. The albumin-bound paclitaxel, Abraxane®, is one of the several therapeutic nanocarriers that have been approved for clinical use. By the development of Abraxane® that demonstrates a higher response rate and improved tolerability and therapeutic efficiency in comparison with solvent-based formulation, and with consideration of its commercial success, albumin is attracting the interest of many biotechnological and pharmaceutical companies. This chapter explores the current targeted and nontargeted albumin-based nanoparticles that are in various stages of development for the delivery of therapeutic agents in order to enhance the efficacy of cancer treatment. © 2015 Elsevier Inc. All rights reserved.01/2015; 98:121-43. DOI:10.1016/bs.apcsb.2014.11.002