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      Combination Treatment of Cervical Cancer Using Folate-Decorated, pH-Sensitive, Carboplatin and Paclitaxel Co-Loaded Lipid-Polymer Hybrid Nanoparticles

      1 , 2 , 3

      Drug Design, Development and Therapy

      Dove

      cervical cancer, folate, pH-sensitive, carboplatin, paclitaxel, lipid-polymer hybrid nanoparticles

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          Abstract

          Purpose

          Cervical cancer is one of the most common causes of death among women globally. Combinations of cisplatin, paclitaxel, bevacizumab, carboplatin, topotecan, and gemcitabine are recommended as first-line therapies.

          Methods

          This study focuses on the development of folate-decorated, pH-sensitive lipid-polymer hybrid nanoparticles (LPNs). Loading carboplatin (CBP) and paclitaxel (PTX), LPNs were expected to combine the therapeutic effects of CBP and PTX, thus show synergistic ability on cervical cancer.

          Results

          FA-CBP/PTX-LPNs showed the sizes of 169.9 ± 5.6 nm, with a narrow size distribution of 0.151 ± 0.023. FA-CBP/PTX-LPNs exhibited pH-responsive drug release, high cellular uptake efficiency (66.7 ± 3.1%), and prominent cell inhibition capacity (23 ± 1.1%). In vivo tumor distribution and tumor inhibition efficiency of FA-CBP/PTX-LPNs was the highest, with no obvious body weight lost.

          Conclusion

          High tumor distribution and remarkable antitumor efficiency obtained using in vitro as well as in vivo models further proved the FA-CBP/PTX-LPNs is a promising tool for cervical cancer therapy.

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          Most cited references 38

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          Co-delivery of doxorubicin and curcumin by pH-sensitive prodrug nanoparticle for combination therapy of cancer

          Ample attention has focused on cancer drug delivery via prodrug nanoparticles due to their high drug loading property and comparatively lower side effects. In this study, we designed a PEG-DOX-Cur prodrug nanoparticle for simultaneous delivery of doxorubicin (DOX) and curcumin (Cur) as a combination therapy to treat cancer. DOX was conjugated to PEG by Schiff’s base reaction. The obtained prodrug conjugate could self-assemble in water at pH 7.4 into nanoparticles (PEG-DOX NPs) and encapsulate Cur into the core through hydrophobic interaction (PEG-DOX-Cur NPs). When the PEG-DOX-Cur NPs are internalized by tumor cells, the Schiff’s base linker between PEG and DOX would break in the acidic environment that is often observed in tumors, causing disassembling of the PEG-DOX-Cur NPs and releasing both DOX and Cur into the nuclei and cytoplasma of the tumor cells, respectively. Compared with free DOX, free Cur, free DOX-Cur combination, or PEG-DOX NPs, PEG-DOX-Cur NPs exhibited higher anti-tumor activity in vitro. In addition, the PEG-DOX-Cur NPs also showed prolonged blood circulation time, elevated local drug accumulation and increased tumor penetration. Enhanced anti-tumor activity was also observed from the PEG-DOX-Cur-treated animals, demonstrating better tumor inhibitory property of the NPs. Thus, the PEG-DOX-Cur prodrug nanoparticle system provides a simple yet efficient approach of drug delivery for chemotherapy.
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            Comparative efficacy, acceptability, and tolerability of lisdexamfetamine in child and adolescent ADHD: a meta-analysis of randomized, controlled trials.

             Maneeton,  DeRosa,  SE Sedykh (2015)
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              Combination of graphene oxide–silver nanoparticle nanocomposites and cisplatin enhances apoptosis and autophagy in human cervical cancer cells

              Background Cisplatin (Cis) is a widely used chemotherapeutic drug for treating a variety of cancers, due to its ability to induce cell death in cancer cells significantly. Recently, graphene and its modified nanocomposites have gained much interest in cancer therapy, due to their unique physicochemical properties. The objective of this study was to investigate the combination effect of Cis and a reduced graphene oxide–silver nanoparticle nanocomposite (rGO-AgNPs) in human cervical cancer (HeLa) cells. Materials and methods We synthesized AgNPs, rGO, and rGO-AgNP nanocomposites using C-phycocyanin. The synthesized nanomaterials were characterized using various analytical techniques. The anticancer properties of the Cis, rGO-AgNPs, and combination of Cis and rGO-AgNPs were evaluated using a series of cellular assays, such as cell viability, cell proliferation, LDH leakage, reactive oxygen species generation, and cellular levels of oxidative and antioxidative stress markers such as malondialdehyde, glutathione, SOD, and CAT. The expression of proapoptotic, antiapoptotic, and autophagy genes were measured using real-time reverse-transcription polymerase chain reaction. Results The synthesized AgNPs were well dispersed, homogeneous, and spherical, with an average size of 10 nm and uniformly distributed on graphene sheets. Cis, GO, rGO, AgNPs, and rGO-AgNPs inhibited cell viability in a dose-dependent manner. The combination of Cis and rGO-AgNPs showed significant effects on cell proliferation, cytotoxicity, and apoptosis. The combination of Cis and rGO-AgNPs had more pronounced effects on the expression of apoptotic and autophagy genes, and also significantly induced the accumulation of autophagosomes and autophagolysosomes, which was associated with the generation of reactive oxygen species. Conclusion Our findings substantiated rGO-AgNPs strongly potentiating Cis-induced cytotoxicity, apoptosis, and autophagy in HeLa cells, and hence rGO-AgNPs could be potentially applied to cervical cancer treatment as a powerful synergistic agent with Cis or any other chemotherapeutic agents.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                DDDT
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                26 February 2020
                2020
                : 14
                : 823-832
                Affiliations
                [1 ]Institution of Cancer and Basic Medicine, Chinese Academy of Sciences , Hangzhou 310022, Zhejiang Province, People’s Republic of China
                [2 ]Department of Gynecological Surgery, Cancer Hospital of the University of Chinese Academy of Sciences , Hangzhou 310022, Zhejiang Province, People’s Republic of China
                [3 ]Department of Gynecological Surgery, Zhejiang Cancer Hospital , Hangzhou 310022, Zhejiang Province, People’s Republic of China
                Author notes
                Correspondence: Junjian Wang Institution of Cancer and Basic Medicine, Chinese Academy of Sciences , No. 1 East Banshan Road, Gongshu District, Hangzhou City, Zhejiang Province, People’s Republic of China Email wangjunjian@protonmail.com
                Article
                235098
                10.2147/DDDT.S235098
                7049774
                © 2020 Wang.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 7, Tables: 1, References: 47, Pages: 10
                Categories
                Original Research

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