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      • Record: found
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      Is Open Access

      Engineering Nanoparticles for Targeted Delivery of Nucleic Acid Therapeutics in Tumor

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          Abstract

          In the past 10 years, with the increase of investment in clinical nano-gene therapy, there are many trials that have been discontinued due to poor efficacy and serious side effects. Therefore, it is particularly important to design a suitable gene delivery system. In this paper, we introduce the application of liposomes, polymers, and inorganics in gene delivery; also, different modifications with some stimuli-responsive systems can effectively improve the efficiency of gene delivery and reduce cytotoxicity and other side effects. Besides, the co-delivery of chemotherapy drugs with a drug tolerance-related gene or oncogene provides a better theoretical basis for clinical cancer gene therapy.

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          Most cited references173

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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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            Nonviral vectors for gene delivery.

            Meredith A. Mintzer, Eric Simanek (2009)
            Article 0 comments Cited 431 times – based on 0 reviews     Review now
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              To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine?

              F Danhier (2016)
              Tumor targeting by nanomedicine-based therapeutics has emerged as a promising approach to overcome the lack of specificity of conventional chemotherapeutic agents and to provide clinicians the ability to overcome shortcomings of current cancer treatment. The major underlying mechanism of the design of nanomedicines was the Enhanced Permeability and Retention (EPR) effect, considered as the "royal gate" in the drug delivery field. However, after the publication of thousands of research papers, the verdict has been handed down: the EPR effect works in rodents but not in humans! Thus the basic rationale of the design and development of nanomedicines in cancer therapy is failing making it necessary to stop claiming efficacy gains via the EPR effect, while tumor targeting cannot be proved in the clinic. It is probably time to dethrone the EPR effect and to ask the question: what is the future of nanomedicines without the EPR effect? The aim of this review is to provide a general overview on (i) the current state of the EPR effect, (ii) the future of nanomedicine and (iii) the strategies of modulation of the tumor microenvironment to improve the delivery of nanomedicine.
              Article 0 comments Cited 401 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Zhiyong Qian
                Journal
                Journal ID (nlm-ta): Mol Ther Methods Clin Dev
                Journal ID (iso-abbrev): Mol Ther Methods Clin Dev
                Title: Molecular Therapy. Methods & Clinical Development
                Publisher: American Society of Gene & Cell Therapy
                ISSN (Electronic): 2329-0501
                Publication date PMC-release: 22 September 2018
                Publication date Collection: 15 March 2019
                Publication date (Electronic): 22 September 2018
                Volume: 12
                Pages: 1-18
                Affiliations
                [1 ]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center, Chengdu, China
                Author notes
                [∗ ]Corresponding author Zhiyong Qian, Sichuan University, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Chengdu 610041, China. anderson-qian@ 123456163.com
                Article
                Publisher ID: S2329-0501(18)30093-7
                DOI: 10.1016/j.omtm.2018.09.002
                PMC ID: 6197778
                SO-VID: d3087c56-95db-4315-9ed5-22fad2dac3e9
                Copyright © © 2018 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Categories
                Subject: Article

                Keywords: gene delivery,nanoparticles,tumor therapy,liposome,polymers,inorganics stimuli response,co-delivery,cellular uptake,nuclear entry
                Data availability:
                Keywords: gene delivery, nanoparticles, tumor therapy, liposome, polymers, inorganics stimuli response, co-delivery, cellular uptake, nuclear entry

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