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      Targeting of drugs and nanoparticles to tumors

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          Abstract

          The various types of cells that comprise the tumor mass all carry molecular markers that are not expressed or are expressed at much lower levels in normal cells. These differentially expressed molecules can be used as docking sites to concentrate drug conjugates and nanoparticles at tumors. Specific markers in tumor vessels are particularly well suited for targeting because molecules at the surface of blood vessels are readily accessible to circulating compounds. The increased concentration of a drug in the site of disease made possible by targeted delivery can be used to increase efficacy, reduce side effects, or achieve some of both. We review the recent advances in this delivery approach with a focus on the use of molecular markers of tumor vasculature as the primary target and nanoparticles as the delivery vehicle.

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          Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance.

          L. Hirsch, R Stafford, J. Bankson … (2011)
          Metal nanoshells are a class of nanoparticles with tunable optical resonances. In this article, an application of this technology to thermal ablative therapy for cancer is described. By tuning the nanoshells to strongly absorb light in the near infrared, where optical transmission through tissue is optimal, a distribution of nanoshells at depth in tissue can be used to deliver a therapeutic dose of heat by using moderately low exposures of extracorporeally applied near-infrared (NIR) light. Human breast carcinoma cells incubated with nanoshells in vitro were found to have undergone photothermally induced morbidity on exposure to NIR light (820 nm, 35 W/cm2), as determined by using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of NIR illumination. Likewise, in vivo studies under magnetic resonance guidance revealed that exposure to low doses of NIR light (820 nm, 4 W/cm2) in solid tumors treated with metal nanoshells reached average maximum temperatures capable of inducing irreversible tissue damage (DeltaT = 37.4 +/- 6.6 degrees C) within 4-6 min. Controls treated without nanoshells demonstrated significantly lower average temperatures on exposure to NIR light (DeltaT < 10 degrees C). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining, which are indicators of irreversible thermal damage. Control tissues appeared undamaged.
          Article 0 comments Cited 673 times – based on 0 reviews     Review now
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            Biodegradable luminescent porous silicon nanoparticles for in vivo applications.

            Ji-Ho Park, Luo Gu, Geoffrey von Maltzahn … (2009)
            Nanomaterials that can circulate in the body hold great potential to diagnose and treat disease. For such applications, it is important that the nanomaterials be harmlessly eliminated from the body in a reasonable period of time after they carry out their diagnostic or therapeutic function. Despite efforts to improve their targeting efficiency, significant quantities of systemically administered nanomaterials are cleared by the mononuclear phagocytic system before finding their targets, increasing the likelihood of unintended acute or chronic toxicity. However, there has been little effort to engineer the self-destruction of errant nanoparticles into non-toxic, systemically eliminated products. Here, we present luminescent porous silicon nanoparticles (LPSiNPs) that can carry a drug payload and of which the intrinsic near-infrared photoluminescence enables monitoring of both accumulation and degradation in vivo. Furthermore, in contrast to most optically active nanomaterials (carbon nanotubes, gold nanoparticles and quantum dots), LPSiNPs self-destruct in a mouse model into renally cleared components in a relatively short period of time with no evidence of toxicity. As a preliminary in vivo application, we demonstrate tumour imaging using dextran-coated LPSiNPs (D-LPSiNPs). These results demonstrate a new type of multifunctional nanostructure with a low-toxicity degradation pathway for in vivo applications.
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              Long-circulating and target-specific nanoparticles: theory to practice.

              S M Moghimi, A C Hunter, J C Murray (2001)
              The rapid recognition of intravenously injected colloidal carriers, such as liposomes and polymeric nanospheres from the blood by Kupffer cells, has initiated a surge of development for "Kupffer cell-evading" or long-circulating particles. Such carriers have applications in vascular drug delivery and release, site-specific targeting (passive as well as active targeting), as well as transfusion medicine. In this article we have critically reviewed and assessed the rational approaches in the design as well as the biological performance of such constructs. For engineering and design of long-circulating carriers, we have taken a lead from nature. Here, we have explored the surface mechanisms, which affords red blood cells long-circulatory lives and the ability of specific microorganisms to evade macrophage recognition. Our analysis is then centered where such strategies have been translated and fabricated to design a wide range of particulate carriers (e.g., nanospheres, liposomes, micelles, oil-in-water emulsions) with prolonged circulation and/or target specificity. With regard to the targeting issues, attention is particularly focused on the importance of physiological barriers and disease states.
              Article 0 comments Cited 310 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Cell Biol
                Journal ID (iso-abbrev): J. Cell Biol
                Journal ID (hwp): jcb
                Title: The Journal of Cell Biology
                Publisher: The Rockefeller University Press
                ISSN (Print): 0021-9525
                ISSN (Electronic): 1540-8140
                Publication date (Print): 22 March 2010
                Volume: 188
                Issue: 6
                Pages: 759-768
                Affiliations
                [1 ]Vascular Mapping Center, Sanford-Burnham Medical Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106
                [2 ]Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037
                [3 ]Department of Health Sciences and Technology , [4 ]Department of Electrical Engineering and Computer Science , and [5 ]The Koch Institute, Massachusetts Institute of Technology, Cambridge, MA 02139
                [6 ]Howard Hughes Medical Institute and [7 ]Division of Medicine, Brigham and Women's Hospital, Boston, MA 02115
                [8 ]Department of Chemistry and Biochemistry , [9 ]Department of Bioengineering , and [10 ]Materials Science and Engineering Program, University of California, San Diego, La Jolla, CA 92093
                Author notes
                Correspondence to Erkki Ruoslahti: ruoslahti@ 123456burnham.org
                Article
                Publisher ID: 200910104
                DOI: 10.1083/jcb.200910104
                PMC ID: 2845077
                PubMed ID: 20231381
                SO-VID: a9127958-ab05-4a96-ba77-8e9c37913959
                Copyright © © 2010 Ruoslahti et al.
                License:

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

                History
                Date received : 19 October 2009
                Date accepted : 19 February 2010
                Categories
                Subject: Reviews
                Subject: Review

                ScienceOpen disciplines: Cell biology
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                ScienceOpen disciplines: Cell biology

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