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Nanomaterial standards for efficacy and toxicity assessment
Author(s) -
Adiseshaiah Pavan P.,
Hall Jennifer B.,
McNeil Scott E.
Publication year - 2009
Publication title -
wiley interdisciplinary reviews: nanomedicine and nanobiotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 72
eISSN - 1939-0041
pISSN - 1939-5116
DOI - 10.1002/wnan.66
Subject(s) - nanomedicine , tumor microenvironment , cancer cell , cancer , nanoparticle , toxicity , in vivo , nanotechnology , cancer research , cytotoxicity , chemistry , biophysics , in vitro , materials science , pharmacology , medicine , tumor cells , biology , biochemistry , microbiology and biotechnology
Abstract Decreased toxicity via selective delivery of cancer therapeutics to tumors has become a hallmark achievement of nanotechnology. In order to be optimally efficacious, a systemically administered nanomedicine must reach cancer cells in sufficient quantities to elicit a response and assume its active form within the tumor microenvironment (e.g., be taken up by cancer cells and release a toxic component once within the cytosol or nuclei). Most nanomedicines achieve selective tumor accumulation via the enhanced permeability and retention (EPR) effect or a combination of the EPR effect and active targeting to cellular receptors. Here, we review how the fundamental physicochemical properties of a nanomedicine (its size, charge, hydrophobicity, etc.) can dramatically affect its distribution to cancerous tissue, transport across vascular walls, and retention in tumors. We also discuss how nanoparticle characteristics such as stability in the blood and tumor, cleavability of covalently bound components, cancer cell uptake, and cytotoxicity contribute to efficacy once the nanoparticle has reached the tumor's interstitial space. We elaborate on how tumor vascularization and receptor expression vary depending on cancer type, stage of disease, site of implantation, and host species, and review studies which have demonstrated that these variations affect tumor response to nanomedicines. Finally, we show how knowledge of these properties (both of the nanoparticle and the cancer/tumor under study) can be used to design meaningful in vivo tests to evaluate nanoparticle efficacy. WIREs Nanomed Nanobiotechnol 2010 2 99–112 This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials