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      Understanding of the Entry Mechanism of Nanoparticles into Tumors Determines the Future Direction of Nanomedicine Development

      , 1 , 2 , , 3 , 4

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          Most cited references 18

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          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.
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            Analysis of nanoparticle delivery to tumours

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              The entry of nanoparticles into solid tumours

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                Author and article information

                Journal
                BIOI
                BIO Integration
                BIOI
                Compuscript (Ireland )
                2712-0082
                2712-0074
                01 January 2021
                22 December 2020
                : 1
                : 4
                : 193-195
                Affiliations
                1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
                2Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
                3Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon 34141, Korea
                4Center for Precision Bio-Nanomedicine, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon 34141, Korea
                Author notes
                *Correspondence to: Phei Er Saw, E-mail: caipeie@ 123456mail.sysu.edu.cn ; Sangyong Jon, E-mail: syjon@ 123456kaist.ac.kr
                Article
                bioi20200033
                10.15212/bioi-2020-0033
                Copyright © 2020 The Authors

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See https://bio-integration.org/copyright-and-permissions/

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