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      The Targeted Delivery of Multicomponent Cargos to Cancer Cells via Nanoporous Particle-Supported Lipid Bilayers

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability, and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma (HCC) exhibit a 10,000-fold greater affinity for HCC than for hepatocytes, endothelial cells, and immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, siRNA, and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer allow a single protocell loaded with a drug cocktail to kill a drug-resistant HCC cell, representing a 10 6-fold improvement over comparable liposomes.

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          A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs.

          Y Matsumura, H. Maeda (1986)
          We previously found that a polymer conjugated to the anticancer protein neocarzinostatin, named smancs, accumulated more in tumor tissues than did neocarzinostatin. To determine the general mechanism of this tumoritropic accumulation of smancs and other proteins, we used radioactive (51Cr-labeled) proteins of various molecular sizes (Mr 12,000 to 160,000) and other properties. In addition, we used dye-complexed serum albumin to visualize the accumulation in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of these mice, and a ratio of the protein concentration in the tumor to that in the blood of 5 was obtained within 19 to 72 h. A large protein like immunoglobulin G required a longer time to reach this value of 5. The protein concentration ratio in the tumor to that in the blood of neither 1 nor 5 was achieved with neocarzinostatin, a representative of a small protein (Mr 12,000) in all time. We speculate that the tumoritropic accumulation of these proteins resulted because of the hypervasculature, an enhanced permeability to even macromolecules, and little recovery through either blood vessels or lymphatic vessels. This accumulation of macromolecules in the tumor was also found after i.v. injection of an albumin-dye complex (Mr 69,000), as well as after injection into normal and tumor tissues. The complex was retained only by tumor tissue for prolonged periods. There was little lymphatic recovery of macromolecules from tumor tissue. The present finding is of potential value in macromolecular tumor therapeutics and diagnosis.
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            Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties.

            Tian Xia, Michael Kovochich, Monty Liong … (2008)
            Nanomaterials (NM) exhibit novel physicochemical properties that determine their interaction with biological substrates and processes. Three metal oxide nanoparticles that are currently being produced in high tonnage, TiO(2), ZnO, and CeO(2), were synthesized by flame spray pyrolysis process and compared in a mechanistic study to elucidate the physicochemical characteristics that determine cellular uptake, subcellular localization, and toxic effects based on a test paradigm that was originally developed for oxidative stress and cytotoxicity in RAW 264.7 and BEAS-2B cell lines. ZnO induced toxicity in both cells, leading to the generation of reactive oxygen species (ROS), oxidant injury, excitation of inflammation, and cell death. Using ICP-MS and fluorescent-labeled ZnO, it is found that ZnO dissolution could happen in culture medium and endosomes. Nondissolved ZnO nanoparticles enter caveolae in BEAS-2B but enter lysosomes in RAW 264.7 cells in which smaller particle remnants dissolve. In contrast, fluorescent-labeled CeO(2) nanoparticles were taken up intact into caveolin-1 and LAMP-1 positive endosomal compartments, respectively, in BEAS-2B and RAW 264.7 cells, without inflammation or cytotoxicity. Instead, CeO(2) suppressed ROS production and induced cellular resistance to an exogenous source of oxidative stress. Fluorescent-labeled TiO(2) was processed by the same uptake pathways as CeO(2) but did not elicit any adverse or protective effects. These results demonstrate that metal oxide nanoparticles induce a range of biological responses that vary from cytotoxic to cytoprotective and can only be properly understood by using a tiered test strategy such as we developed for oxidative stress and adapted to study other aspects of nanoparticle toxicity.
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              Mesoporous materials for drug delivery.

              María Vallet-Regí, Francisco Balas, Daniel Arcos (2007)
              Research on mesoporous materials for biomedical purposes has experienced an outstanding increase during recent years. Since 2001, when MCM-41 was first proposed as drug-delivery system, silica-based materials, such as SBA-15 or MCM-48, and some metal-organic frameworks have been discussed as drug carriers and controlled-release systems. Mesoporous materials are intended for both systemic-delivery systems and implantable local-delivery devices. The latter application provides very promising possibilities in the field of bone-tissue repair because of the excellent behavior of these materials as bioceramics. This Minireview deals with the advances in this field by the control of the textural parameters, surface functionalization, and the synthesis of sophisticated stimuli-response systems.
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 101155473
                Journal ID (pubmed-jr-id): 30248
                Journal ID (nlm-ta): Nat Mater
                Title: Nature Materials
                ISSN (Print): 1476-1122
                ISSN (Electronic): 1476-1122
                Publication date Nihms-submitted: 12 April 2011
                Publication date (Electronic): 17 April 2011
                Publication date (Print): May 2011
                Publication date PMC-release: 27 February 2012
                Volume: 10
                Issue: 5
                Pages: 389-397
                Affiliations
                [1 ]Center for Micro-Engineered Materials, the University of New Mexico, Albuquerque, NM 87131, USA
                [2 ]Department of Chemical and Nuclear Engineering, the University of New Mexico, Albuquerque, NM 87131, US
                [3 ]Cancer Research and Treatment Center, the University of New Mexico, Albuquerque, NM 87131, USA
                [4 ]Department of Chemistry, the University of New Mexico, Albuquerque, NM 87131, USA
                [5 ]Department of Chemical Engineering, University of Florida, Gainesville, FL 32611, US
                [6 ]School of Medicine, Department of Pathology, the University of New Mexico, Albuquerque, NM 87131, USA
                [7 ]Department of Molecular Genetics and Microbiology, the University of New Mexico, Albuquerque, NM 87131, USA
                [8 ]Self-Assembled Materials Department, Sandia National Laboratories, Albuquerque, NM 87185-1349, USA
                [9 ]Department of Applied Science, University of California Davis, Davis, CA 95616, USA
                Author notes
                Additional Information. The authors declare no competing financial interests. Correspondence and requests for materials should be addressed to C.E.A ( ceashle@ 123456sandia.gov ) or C.J.B. ( cjbrink@ 123456sandia.gov )
                [†]

                Current Appointment: Harry S. Truman Post-Doctoral Fellow; Biotechnology and Bioengineering Department, Sandia National Laboratories, Livermore, CA 94551, USA.

                [‡]

                Current Address: Department of Chemistry, University of Waterloo, Waterloo, ON, Canada, N2L 3G1.

                Article
                Manuscript ID: nihpa276133
                DOI: 10.1038/nmat2992
                PMC ID: 3287066
                PubMed ID: 21499315
                SO-VID: 03d5dd4b-2b99-4a1d-955b-cfcdf29dbff1
                License:

                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Funding
                Funded by: National Cancer Institute : NCI
                Award ID: U01 CA151792-02 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: U01 CA151792-01 || CA
                Categories
                Subject: Article

                ScienceOpen disciplines: Materials science
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                ScienceOpen disciplines: Materials science

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