Codelivery of Anticancer Drug and Photosensitizer by PEGylated Graphene Oxide and Cell Penetrating Peptide Enhanced Tumor-Suppressing Effect on Osteosarcoma

Overview

Journal Front Mol Biosci

Specialty Biology

Date 2021 Apr 26

PMID 33898510

Citations 5

Authors

Yi-Fei Zhang

Yun-Feng Wu

Tai-Jin Lan

Yao Chen

Shi-Hong Su

Affiliations

Soon will be listed here.

Abstract

Graphene oxide (GO) has been widely used for various biological and biomedical applications due to its unique physiochemical properties. This study aimed to investigate the effects of cell penetrating peptide (CPP) modified and polyethylene-glycol- (PEG-) grafted GO (pGO) loaded with photosensitive agent 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH) and Epirubicin (EPI) (HPPH/EPI/CPP-pGO) on tumor growth in osteosarcoma. The HPPH/EPI/CPP-pGO were prepared, and then in vitro drug release assay was conducted. The detection of singlet oxygen (O) and cellular uptake of HPPH was performed as well. Next, the effects of control (saline solution), CPP-pGO, EPI, HPPH, HPPH/CPP-pGO, EPI/CPP-pGO, HPPH/EPI/pGO, and HPPH/EPI/CPP-pGO were evaluated by MTT assay, colony-forming assay, and cell apoptosis assay in MG-63 cells. Furthermore, the antitumor effects of HPPH/EPI/CPP-pGO on osteosarcoma xenograft mice were unraveled. The O generation and cellular uptake of HPPH were significantly increased after CPP and pGO modification compared with free HPPH. In addition, compared with control cells, CPP-pGO treatment had low cytotoxicity in MG-63 cells. Compared with free HPPH or EPI, HPPH/CPP-pGO or EPI/CPP-pGO treatment significantly inhibited cell viability and colony forming number, as well as inducing cell apoptosis. HPPH/EPI-pGO treatment showed stronger inhibition effects on MG-63 cells than HPPH/CPP-pGO or EPI/CPP-pGO, and HPPH/EPI/CPP-pGO was the most effective one. Similarly, experiments revealed that, compared with control group, the tumor size and weight of osteosarcoma xenograft mice were obviously decreased after free HPPH or EPI treatment, which were further reduced in other groups, especially in HPPH/EPI/CPP-pGO group. HPPH/EPI/CPP-pGO had superior tumor-inhibiting effects and on osteosarcoma.

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References

Tracy E, Bowman M, Pandey R, Baumann H . Cell-specific Retention and Action of Pheophorbide-based Photosensitizers in Human Lung Cancer Cells. Photochem Photobiol. 2018; 95(3):846-859. PMC: 6496943. DOI: 10.1111/php.13043. View

Shafirstein G, Rigual N, Arshad H, Cooper M, Bellnier D, Wilding G . Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide-a for early-stage cancer of the larynx: Phase Ib study. Head Neck. 2015; 38 Suppl 1:E377-83. PMC: 4499022. DOI: 10.1002/hed.24003. View

Zhi F, Dong H, Jia X, Guo W, Lu H, Yang Y . Functionalized graphene oxide mediated adriamycin delivery and miR-21 gene silencing to overcome tumor multidrug resistance in vitro. PLoS One. 2013; 8(3):e60034. PMC: 3603917. DOI: 10.1371/journal.pone.0060034. View

Ozog D, Rkein A, Fabi S, Gold M, Goldman M, Lowe N . Photodynamic Therapy: A Clinical Consensus Guide. Dermatol Surg. 2016; 42(7):804-27. DOI: 10.1097/DSS.0000000000000800. View

Fink C, Enk A, Gholam P . Photodynamic therapy--aspects of pain management. J Dtsch Dermatol Ges. 2015; 13(1):15-22. DOI: 10.1111/ddg.12546. View

Dorniani D, Saifullah B, Barahuie F, Arulselvan P, Hussein M, Fakurazi S . Graphene Oxide-Gallic Acid Nanodelivery System for Cancer Therapy. Nanoscale Res Lett. 2016; 11(1):491. PMC: 5099306. DOI: 10.1186/s11671-016-1712-2. View

Duzgunes N, Piskorz J, Skupin-Mrugalska P, Goslinski T, Mielcarek J, Konopka K . Photodynamic therapy of cancer with liposomal photosensitizers. Ther Deliv. 2018; 9(11):823-832. DOI: 10.4155/tde-2018-0050. View

Zhang L, Zhang Y, Tai L, Jiang K, Xie C, Li Z . Functionalized cell nucleus-penetrating peptide combined with doxorubicin for synergistic treatment of glioma. Acta Biomater. 2016; 42:90-101. DOI: 10.1016/j.actbio.2016.06.031. View

Dubikovskaya E, Thorne S, Pillow T, Contag C, Wender P . Overcoming multidrug resistance of small-molecule therapeutics through conjugation with releasable octaarginine transporters. Proc Natl Acad Sci U S A. 2008; 105(34):12128-33. PMC: 2527877. DOI: 10.1073/pnas.0805374105. View

10.

Izgi K, Iskender B, Sakalar C, Arslanhan A, Yuksek E, Hizar E . Effects of Epirubicin and Cisplatin Against 4T1 Breast Cancer Cells are Enhanced by Myrtucommulone-A. Anticancer Agents Med Chem. 2016; 17(3):404-414. DOI: 10.2174/1871520616666160404110543. View

11.

Lv Y, Tao L, Bligh S, Yang H, Pan Q, Zhu L . Targeted delivery and controlled release of doxorubicin into cancer cells using a multifunctional graphene oxide. Mater Sci Eng C Mater Biol Appl. 2015; 59:652-660. DOI: 10.1016/j.msec.2015.10.065. View

12.

Candido N, de Melo M, Franchi L, Primo F, Tedesco A, Rahal P . Combining Photodynamic Therapy and Chemotherapy: Improving Breast Cancer Treatment with Nanotechnology. J Biomed Nanotechnol. 2018; 14(5):994-1008. DOI: 10.1166/jbn.2018.2558. View

13.

Harrison D, Geller D, Gill J, Lewis V, Gorlick R . Current and future therapeutic approaches for osteosarcoma. Expert Rev Anticancer Ther. 2017; 18(1):39-50. DOI: 10.1080/14737140.2018.1413939. View

14.

Yu L, Meng M, Bao Y, Zhang C, Gao B, Sa R . miR-1301/TRIAP1 Axis Participates in Epirubicin-Mediated Anti-Proliferation and Pro-Apoptosis in Osteosarcoma. Yonsei Med J. 2019; 60(9):832-841. PMC: 6704023. DOI: 10.3349/ymj.2019.60.9.832. View

15.

Rosli N, Fojtu M, Fisher A, Pumera M . Graphene Oxide Nanoplatelets Potentiate Anticancer Effect of Cisplatin in Human Lung Cancer Cells. Langmuir. 2019; 35(8):3176-3182. DOI: 10.1021/acs.langmuir.8b03086. View

16.

Cao X, Yang X, Du X, Fu L, Zhang T, Shan H . Structure optimisation to improve the delivery efficiency and cell selectivity of a tumour-targeting cell-penetrating peptide. J Drug Target. 2018; 26(9):777-792. DOI: 10.1080/1061186X.2018.1424858. View

17.

Stock E, Ferrara C, OConnor P, Naya-Vigne J, Frost P, Malloy M . Levels of prebeta-1 high-density lipoprotein are elevated in 3 phenotypes of dyslipidemia. J Clin Lipidol. 2017; 12(1):99-109. DOI: 10.1016/j.jacl.2017.11.001. View

18.

Pan X, Su F, Xu L, Yang Z, Wang D, Yang L . DJ-1 Alters Epirubicin-induced Apoptosis via Modulating Epirubicinactivated Autophagy in Human Gastric Cancer Cells. Curr Med Sci. 2018; 38(6):1018-1024. DOI: 10.1007/s11596-018-1978-y. View

19.

Hwang D, Kim H, Li F, Park J, Kim D, Park J . In vivo visualization of endogenous miR-21 using hyaluronic acid-coated graphene oxide for targeted cancer therapy. Biomaterials. 2017; 121:144-154. DOI: 10.1016/j.biomaterials.2016.12.028. View

20.

Cacan E, Ozmen Z . Regulation of Fas in response to bortezomib and epirubicin in colorectal cancer cells. J Chemother. 2020; 32(4):193-201. DOI: 10.1080/1120009X.2020.1740389. View