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      A multifunctional nanoplatform for cancer chemo-photothermal synergistic therapy and overcoming multidrug resistance

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          A multifunctional nanoplatform could overcome multidrug resistance and showed cancer chemo-photothermal synergistic therapy with the near-infrared irradiation.


          The integration of various therapy strategies into a single nanoplatform for synergistic cancer treatment has presented a great prospect. Herein, docetaxel (DTX)-loaded poly lactic- co-glycolic acid (PLGA)-coated polydopamine modified with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) was synthesized for chemo-photothermal synergistic therapy against cancer. Firstly, the DTX-loaded PLGA NPs were prepared by a facile and robust nanoprecipitation method. Then, they were coated with dopamine to achieve the photothermal effects and to be further modified with TPGS, which can inhibit the P-glycoprotein-mediated multidrug resistance (MDR). The near-infrared (NIR) laser irradiation triggered DTX release from DTX-loaded PLGA NPs@PDA-TPGS, and then the chemo-photothermal therapy effect could be enhanced. The in vitro experimental results illustrated that DTX-loaded PLGA NPs@PDA-TPGS exhibits excellent photothermal conservation properties and remarkable cell-killing efficiency. In vivo antitumor studies further confirmed that DTX-loaded PLGA NPs@PDA-TPGS could present an outstanding synergistic antitumor efficacy compared with any monotherapy. This work exhibits a novel nanoplatform, which could not only load chemotherapy drugs efficiently, but could also improve the therapeutic effect of chemotherapy drugs by overcoming MDR and light-mediated photothermal cancer therapy.

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          Most cited references 49

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          Here we systematically examined the effect of nanoparticle size (10-100 nm) and surface chemistry (i.e., poly(ethylene glycol)) on passive targeting of tumors in vivo. We found that the physical and chemical properties of the nanoparticles influenced their pharmacokinetic behavior, which ultimately determined their tumor accumulation capacity. Interestingly, the permeation of nanoparticles within the tumor is highly dependent on the overall size of the nanoparticle, where larger nanoparticles appear to stay near the vasculature while smaller nanoparticles rapidly diffuse throughout the tumor matrix. Our results provide design parameters for engineering nanoparticles for optimized tumor targeting of contrast agents and therapeutics.
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            Dopamine-melanin colloidal nanospheres: an efficient near-infrared photothermal therapeutic agent for in vivo cancer therapy.

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              Soluble polymer carriers for the treatment of cancer: the importance of molecular architecture.

              Chemotherapy can destroy tumors and arrest cancer progress. Unfortunately, severe side effects (treatment is usually a series of injections of highly toxic drugs) often restrict the frequency and size of dosages, much to the detriment of tumor inhibition. Most chemotherapeutic drugs have pharmacokinetic profiles with tremendous potential for improvement. Water-soluble polymers offer the potential to increase drug circulation time, improve drug solubility, prolong drug residence time in a tumor, and reduce toxicity. Cytotoxic drugs that are covalently attached to water-soluble polymers via reversible linkages more effectively target tumor tissue than the drugs alone. Macromolecules passively target solid tumor tissue through a combination of reduced renal clearance and exploitation of the enhanced permeation and retention (EPR) effect, which prevails for fast-growing tumors. Effective drug delivery involves a balance between (i) elimination of the polymeric drug conjugate from the bloodstream by the kidneys, liver, and other organs and (ii) movement of the drug out of the blood vasculature and into the tumor (that is, extravasation). Polymers are eliminated in the kidney by filtration through pores with a size comparable to the hydrodynamic diameter of the polymer; in contrast, the openings in the blood vessel structures that traverse tumors are an order of magnitude greater than the diameter of the polymer. Thus, features that may broadly be grouped as the "molecular architecture" of the polymer, such as its hydrodynamic volume (or molecular weight), molecular conformation, chain flexibility, branching, and location of the attached drug, can greatly impact elimination of the polymer from the body through the kidney but have a much smaller effect on the extravasation of the polymer into the tumor. Molecular architecture can in theory be adjusted to assert essentially independent control over elimination and extravasation. Understanding how molecular architecture affects passage of a polymer through a pore is therefore essential for designing polymer drug carriers that are effective in passively delivering a drug payload while conforming to the requirement that the polymers must eventually be eliminated from the body. In this Account, we discuss examples from in vivo studies that demonstrate how polymer architectural features impact the renal filtration of a polymer as well as tumor penetration and tumor accumulation. In brief, features that inhibit passage of a polymer through a pore, such as higher molecular weight, decreased flexibility, and an increased number of polymer chain ends, help prevent elimination of the polymer by the kidneys and can improve blood circulation times and tumor accumulation, thus improving therapeutic effectiveness.

                Author and article information

                Biomaterials Science
                Biomater. Sci.
                Royal Society of Chemistry (RSC)
                : 6
                : 5
                : 1084-1098
                [1 ]School of Life Sciences
                [2 ]Tsinghua University
                [3 ]Beijing 100084
                [4 ]China
                [5 ]Division of Life and Health Sciences
                [6 ]Graduate School at Shenzhen
                [7 ]Shenzhen 518055
                [8 ]School of Pharmaceutical Sciences (Shenzhen)
                [9 ]Sun Yat-sen University
                [10 ]Guangzhou 510275
                [11 ]Institute of Biomedical Engineering
                [12 ]Chinese Academy of Medical Sciences & Peking Union Medical College
                [13 ]Tianjin Key Laboratory of Biomedical Materials
                [14 ]Tianjin 300192
                © 2018
                Self URI (article page): http://xlink.rsc.org/?DOI=C7BM01206C


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