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      Progress and challenges towards targeted delivery of cancer therapeutics

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          Abstract

          Targeted delivery approaches for cancer therapeutics have shown a steep rise over the past few decades. However, compared to the plethora of successful pre-clinical studies, only 15 passively targeted nanocarriers (NCs) have been approved for clinical use and none of the actively targeted NCs have advanced past clinical trials. Herein, we review the principles behind targeted delivery approaches to determine potential reasons for their limited clinical translation and success. We propose criteria and considerations that must be taken into account for the development of novel actively targeted NCs. We also highlight the possible directions for the development of successful tumor targeting strategies.

          Abstract

          Targeted delivery strategies based on nanocarriers have immense potential to change cancer care but current strategies have been shown only limited translation in the clinic. Here, the authors survey the challenge, progress and opportunities towards targeted delivery of cancer therapeutics.

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          Most cited references63

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          Analysis of nanoparticle delivery to tumours

          Stefan Wilhelm, Anthony Tavares, Huan-Qin Dai … (2016)
          Article 0 comments Cited 1286 times – based on 0 reviews     Review now
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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.
            Article 0 comments Cited 1009 times – based on 0 reviews     Review now
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              Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer.

              William Gradishar, Sergei Tjulandin, Neville Davidson … (2005)
              ABI-007, the first biologically interactive albumin-bound paclitaxel in a nanameter particle, free of solvents, was compared with polyethylated castor oil-based standard paclitaxel in patients with metastatic breast cancer (MBC). This phase III study was performed to confirm preclinical studies demonstrating superior efficacy and reduced toxicity of ABI-007 compared with standard paclitaxel. Patients were randomly assigned to 3-week cycles of either ABI-007 260 mg/m(2) intravenously without premedication (n = 229) or standard paclitaxel 175 mg/m(2) intravenously with premedication (n = 225). ABI-007 demonstrated significantly higher response rates compared with standard paclitaxel (33% v 19%, respectively; P = .001) and significantly longer time to tumor progression (23.0 v 16.9 weeks, respectively; hazard ratio = 0.75; P = .006). The incidence of grade 4 neutropenia was significantly lower for ABI-007 compared with standard paclitaxel (9% v 22%, respectively; P < .001) despite a 49% higher paclitaxel dose. Febrile neutropenia was uncommon (< 2%), and the incidence did not differ between the two study arms. Grade 3 sensory neuropathy was more common in the ABI-007 arm than in the standard paclitaxel arm (10% v 2%, respectively; P < .001) but was easily managed and improved rapidly (median, 22 days). No hypersensitivity reactions occurred with ABI-007 despite the absence of premedication and shorter administration time. ABI-007 demonstrated greater efficacy and a favorable safety profile compared with standard paclitaxel in this patient population. The improved therapeutic index and elimination of corticosteroid premedication required for solvent-based taxanes make the novel albumin-bound paclitaxel ABI-007 an important advance in the treatment of MBC.
              Article 0 comments Cited 434 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Jeffrey M. Karp: jmkarp@bwh.harvard.edu
                Dan Peer:
                ORCID: http://orcid.org/0000-0001-8238-0673
                peer@tauex.tau.ac.il
                Journal
                Journal ID (nlm-ta): Nat Commun
                Journal ID (iso-abbrev): Nat Commun
                Title: Nature Communications
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2041-1723
                Publication date (Electronic): 12 April 2018
                Publication date PMC-release: 12 April 2018
                Publication date Collection: 2018
                Volume: 9
                Electronic Location Identifier: 1410
                Affiliations
                [1 ]ISNI 0000 0004 1937 0546, GRID grid.12136.37, Laboratory of Precision NanoMedicine, School of Molecular Cell Biology and Biotechnology, George S. Wise Faculty of Life Sciences, Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering; Center for Nanoscience and Nanotechnology, , Cancer Biology Research Center, Tel Aviv University, ; Tel Aviv, 6997801 Israel
                [2 ]Center for Nanomedicine and Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139 USA
                [3 ]ISNI 0000 0004 0475 2760, GRID grid.413735.7, Harvard-Massachusetts Division of Health Science and Technology, ; Cambridge, MA 02139 USA
                [4 ]ISNI 000000041936754X, GRID grid.38142.3c, Center for Nanomedicine and Department of Anesthesiology and, Brigham and Women’s Hospital, , Harvard Medical School, ; Boston, MA 02115 USA
                Author information
                http://orcid.org/0000-0002-4277-3728
                http://orcid.org/0000-0001-8238-0673
                Article
                Publisher ID: 3705
                DOI: 10.1038/s41467-018-03705-y
                PMC ID: 5897557
                PubMed ID: 29650952
                SO-VID: 826fe5f1-7243-418d-9e83-715dad35c059
                Copyright © © The Author(s) 2018
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 21 August 2017
                Date accepted : 5 March 2018
                Categories
                Subject: Review Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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