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      Development and evaluation of novel tumor-targeting paclitaxel-loaded nano-carriers for ovarian cancer treatment: in vitro and in vivo.

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          Abstract

          Ovarian cancer is the most leading cause of death and the third most common gynecologic malignancy in women. Traditional chemotherapy has inevitable drawbacks of nonspecific tumor targeting, high toxicity, and poor therapeutic efficiency. In order to overcome such shortcomings, we prepared a novel nano-carrier drug-delivery system to enhance the anti-tumor efficiency.

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          Most cited references25

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          Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications.

          Cancer is a leading cause of death worldwide. Currently available therapies are inadequate and spur demand for improved technologies. Rapid growth in nanotechnology towards the development of nanomedicine products holds great promise to improve therapeutic strategies against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multi-functionality. They can improve the pharmacokinetic and pharmacodynamic profiles of conventional therapeutics and may thus optimize the efficacy of existing anti-cancer compounds. In this review, we discuss state-of-the-art nanoparticles and targeted systems that have been investigated in clinical studies. We emphasize the challenges faced in using nanomedicine products and translating them from a preclinical level to the clinical setting. Additionally, we cover aspects of nanocarrier engineering that may open up new opportunities for nanomedicine products in the clinic.
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            Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles.

            Nanoparticle drug delivery to the tumor is impacted by multiple factors: nanoparticles must evade clearance by renal filtration and the reticuloendothelial system, extravasate through the enlarged endothelial gaps in tumors, penetrate through dense stroma in the tumor microenvironment to reach the tumor cells, remain in the tumor tissue for a prolonged period of time, and finally release the active agent to induce pharmacological effect. The physicochemical properties of nanoparticles such as size, shape, surface charge, surface chemistry (PEGylation, ligand conjugation) and composition affect the pharmacokinetics, biodistribution, intratumoral penetration and tumor bioavailability. On the other hand, tumor biology (blood flow, perfusion, permeability, interstitial fluid pressure and stroma content) and patient characteristics (age, gender, tumor type, tumor location, body composition and prior treatments) also have impact on drug delivery by nanoparticles. It is now believed that both nanoparticles and the tumor microenvironment have to be optimized or adjusted for optimal delivery. This review provides a comprehensive summary of how these nanoparticle and biological factors impact nanoparticle delivery to tumors, with discussion on how the tumor microenvironment can be adjusted and how patients can be stratified by imaging methods to receive the maximal benefit of nanomedicine. Perspectives and future directions are also provided. © 2013.
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              Folate-targeted therapeutic and imaging agents for cancer.

              Cancer therapies that exploit targeting ligands to deliver attached cytotoxic drugs selectively to malignant cells are currently receiving significant attention. While antibody-targeted drugs have been the first to enter the clinic, recent studies demonstrate that the vitamin folic acid can also be used to deliver attached imaging and therapeutic agents selectively to malignant cells in both animal tumor models and human cancer patients. Thus, folate conjugates bind to folate receptors that are overexpressed on approximately 40% of human cancers and mediate internalization of their attached drugs by receptor-mediated endocytosis. With the use of proper linkers, folate-targeted drugs can be released inside their target cells where they can perform their desired cytotoxic functions. Based on this strategy, six folate-targeted drugs are currently in human clinical trials.
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                Author and article information

                Journal
                J. Exp. Clin. Cancer Res.
                Journal of experimental & clinical cancer research : CR
                Springer Nature America, Inc
                1756-9966
                0392-9078
                Feb 26 2018
                : 37
                : 1
                Affiliations
                [1 ] Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan, Shandong, 250012, People's Republic of China.
                [2 ] Gynecology Oncology Key Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, China.
                [3 ] Department of Biomedical Engineering, School of Control Science and Engineering, Shandong University, Jinan, Shandong, 250012, China.
                [4 ] Department of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong, 250012, China.
                [5 ] Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan, Shandong, 250012, People's Republic of China. songkun2001226@sdu.edu.cn.
                [6 ] Gynecology Oncology Key Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, China. songkun2001226@sdu.edu.cn.
                Article
                10.1186/s13046-018-0700-z
                10.1186/s13046-018-0700-z
                29478415
                5e2413cc-5e15-4531-b852-6116eb7d24cd
                History

                Nano-carriers,Ovarian cancer,Folic acid,Tumor targeting,Paclitaxel

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