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      PSMA-Targeted Supramolecular Nanoparticles Prepared From Cucurbit[8]uril-Based Ternary Host–Guest Recognition for Prostate Cancer Therapy

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          Abstract

          Nanomedicines play an important role in cancer therapy; however, some drawbacks including unsatisfactory efficacy and side effects arising from indiscriminate drug release retard their clinical applications. Although functionalization of nanomedicines through covalent interactions can improve the pharmacokinetics and efficacy of the loaded drugs, complicated and tedious synthesis greatly limits the exploration of multifunctional nanoparticles. Herein, we utilize a supramolecular strategy to design a nanomedicine for targeted drug delivery through cucurbit[8]uril-based host–guest ternary complexation and successfully prepare prostate-specific membrane antigen (PSMA)-targeted supramolecular nanoparticles encapsulating doxorubicin (DOX). In vitro studies exhibit targeted modification via noncovalent enhance anticancer efficiency of DOX due to the increased cell uptake on account of receptor-mediated endocytosis. This design provides a new strategy for the development of sophisticated drug delivery systems and holds perspective potentials in precise cancer treatments.

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          Most cited references45

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          Cancer nanomedicine: progress, challenges and opportunities

          The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a
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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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              Nanocarriers as an emerging platform for cancer therapy.

              Nanotechnology has the potential to revolutionize cancer diagnosis and therapy. Advances in protein engineering and materials science have contributed to novel nanoscale targeting approaches that may bring new hope to cancer patients. Several therapeutic nanocarriers have been approved for clinical use. However, to date, there are only a few clinically approved nanocarriers that incorporate molecules to selectively bind and target cancer cells. This review examines some of the approved formulations and discusses the challenges in translating basic research to the clinic. We detail the arsenal of nanocarriers and molecules available for selective tumour targeting, and emphasize the challenges in cancer treatment.
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                Author and article information

                Contributors
                Journal
                Front Chem
                Front Chem
                Front. Chem.
                Frontiers in Chemistry
                Frontiers Media S.A.
                2296-2646
                10 February 2022
                2022
                : 10
                : 847523
                Affiliations
                [1] 1 School of Life Sciences , Jilin University , Changchun, China
                [2] 2 Lymph and Vascular Surgery Department , China-Japan Union Hospital of Jilin University , Changchun, China
                Author notes

                Edited by: Yong Yao, Nantong University, China

                Reviewed by: Yue Ding, Nantong University, China

                Dan Wu, Zhejiang University of Technology, China

                *Correspondence: Dahai Liu, dahai@ 123456jlu.edu.cn ; Jianshi Du, dujs@ 123456jlu.edu.cn ; Jingji Jin, jjjin@ 123456jlu.edu.cn

                This article was submitted to Supramolecular Chemistry, a section of the journal Frontiers in Chemistry

                Article
                847523
                10.3389/fchem.2022.847523
                8867089
                35223775
                442feeac-02a3-4e43-9277-136a9ad4bfbb
                Copyright © 2022 Zhang, Qi, Liu, Du and Jin.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 January 2022
                : 10 January 2022
                Categories
                Chemistry
                Original Research

                prostate cancer,drug delivery,nanomedicine,host–guest complex,supramolecular chemistry

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