29
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Targeted Delivery to Tumors: Multidirectional Strategies to Improve Treatment Efficiency

      review-article

      Read this article at

      Bookmark
          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

          Malignant tumors are characterized by structural and molecular peculiarities providing a possibility to directionally deliver antitumor drugs with minimal impact on healthy tissues and reduced side effects. Newly formed blood vessels in malignant lesions exhibit chaotic growth, disordered structure, irregular shape and diameter, protrusions, and blind ends, resulting in immature vasculature; the newly formed lymphatic vessels also have aberrant structure. Structural features of the tumor vasculature determine relatively easy penetration of large molecules as well as nanometer-sized particles through a blood–tissue barrier and their accumulation in a tumor tissue. Also, malignant cells have altered molecular profile due to significant changes in tumor cell metabolism at every level from the genome to metabolome. Recently, the tumor interaction with cells of immune system becomes the focus of particular attention, that among others findings resulted in extensive study of cells with preferential tropism to tumor. In this review we summarize the information on the diversity of currently existing approaches to targeted drug delivery to tumor, including (i) passive targeting based on the specific features of tumor vasculature, (ii) active targeting which implies a specific binding of the antitumor agent with its molecular target, and (iii) cell-mediated tumor targeting.

          Related collections

          Most cited references258

          • Record: found
          • Abstract: not found
          • Article: not found

          Analysis of nanoparticle delivery to tumours

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

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

            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.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Progress and challenges towards targeted delivery of cancer therapeutics

              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.
                Bookmark

                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                10 January 2019
                January 2019
                : 11
                : 1
                : 68
                Affiliations
                [1 ]The Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin ave., Nizhny Novgorod 603950, Russia; kutovaom@ 123456gmail.com (O.M.K.); eguryev@ 123456ibbm.unn.ru (E.L.G.); malehanova@ 123456mail.ru (E.A.S.); razanzybak@ 123456gmail.com (R.A.)
                [2 ]The Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, 8-2 Trubetskaya str., Moscow 119991, Russia
                Author notes
                [* ]Correspondence: irin-b@ 123456mail.ru ; Tel.: +7-831-4623-205
                Article
                cancers-11-00068
                10.3390/cancers11010068
                6356537
                30634580
                f84d32f3-d8f1-4805-984b-c3bb07b04142
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 November 2018
                : 07 January 2019
                Categories
                Review

                targeted drug delivery,cancer treatment,epr-effect,passive targeting,cancer-specific molecular targets,active targeting,cell-mediated targeting

                Comments

                Comment on this article