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      Polydopamine-Based “Four-in-One” Versatile Nanoplatforms for Targeted Dual Chemo and Photothermal Synergistic Cancer Therapy

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          Abstract

          The development of versatile nanoscale drug delivery systems that integrate with multiple therapeutic agents or methods and improve the efficacy of cancer therapy is urgently required. To satisfy this demand, polydopamine (PDA)-modified polymeric nanoplatforms were constructed for the dual loading of chemotherapeutic drugs. The hydrophobic anticancer drug docetaxel (DTX) was loaded into the polymeric nanoparticles (NPs) which were fabricated from the star-shaped copolymer CA-PLGA. Then DTX-loaded NPs were coated with PDA, followed by conjugation of polyelethyl glycol (PEG)-modified targeting ligand aptamer AS1411(Apt) and adsorption of the hydrophilic anticancer drug doxorubicin (DOX). This “four-in-one” nanoplatform, referred to as DTX/NPs@PDA/DOX-PEG-Apt, demonstrated high near-infrared photothermal conversion efficiency and exhibited pH and thermo-responsive drug release behavior. Furthermore, it was able to specifically target MCF-7 human breast carcinoma cells and provide synergistic chemo-photothermal therapy to further improve the anticancer effect both in vitro and in vivo, providing a novel promising strategy for cancer therapy.

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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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            Design of polymeric nanoparticles for biomedical delivery applications.

            Polymeric nanoparticles-based therapeutics show great promise in the treatment of a wide range of diseases, due to the flexibility in which their structures can be modified, with intricate definition over their compositions, structures and properties. Advances in polymerization chemistries and the application of reactive, efficient and orthogonal chemical modification reactions have enabled the engineering of multifunctional polymeric nanoparticles with precise control over the architectures of the individual polymer components, to direct their assembly and subsequent transformations into nanoparticles of selective overall shapes, sizes, internal morphologies, external surface charges and functionalizations. In addition, incorporation of certain functionalities can modulate the responsiveness of these nanostructures to specific stimuli through the use of remote activation. Furthermore, they can be equipped with smart components to allow their delivery beyond certain biological barriers, such as skin, mucus, blood, extracellular matrix, cellular and subcellular organelles. This tutorial review highlights the importance of well-defined chemistries, with detailed ties to specific biological hurdles and opportunities, in the design of nanostructures for various biomedical delivery applications.
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              Versatile Polydopamine Platforms: Synthesis and Promising Applications for Surface Modification and Advanced Nanomedicine

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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                01 October 2019
                October 2019
                : 11
                : 10
                : 507
                Affiliations
                [1 ]School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China; liugan5@ 123456mail.sysu.edu.cn (G.L.); gaonsh@ 123456mail.sysu.edu.cn (N.G.); zhouy599@ 123456mail2.sysu.edu.cn (Y.Z.); upc201412@ 123456163.com (W.C.); luomm3@ 123456mail2.sysu.edu.cn (M.L.); meilin7@ 123456mail.sysu.edu.cn (L.M.)
                [2 ]Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China; niejunpeng@ 123456126.com
                Author notes
                [* ]Correspondence: zengxw23@ 123456mail.sysu.edu.cn (X.Z.); dengwb5@ 123456mail.sysu.edu.cn (W.D.); Tel.: +81-20-8472-3750 (W.D.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-6165-3799
                Article
                pharmaceutics-11-00507
                10.3390/pharmaceutics11100507
                6835447
                31581532
                bf79a534-2b91-4a1b-8988-c7d157df39b4
                © 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
                : 11 August 2019
                : 26 September 2019
                Categories
                Article

                synergistic cancer therapy,polydopamine,aptamer,dual drug delivery,photothermal therapy

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