Original articles
Peng Liu, Xin Xie, Miao Liu, Shuo Hu, Jinsong Ding, Wenhu Zhou. A smart MnO2-doped graphene oxide nanosheet for enhanced chemo-photodynamic combinatorial therapy via simultaneous oxygenation and glutathione depletion[J]. Acta Pharmaceutica Sinica B, 2021, 11(3): 823-834

A smart MnO2-doped graphene oxide nanosheet for enhanced chemo-photodynamic combinatorial therapy via simultaneous oxygenation and glutathione depletion
Peng Liua, Xin Xieb, Miao Liua, Shuo Huc,d, Jinsong Dinga, Wenhu Zhoua,b,d
a Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China;
b School of Pharmaceutical Sciences, Gannan Medical University, Ganzhou 341000, China;
c Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha 410008, China;
d Key Laboratory of Biological Nanotechnology of National Health Commission, Changsha 410008, China
Abstract:
The combination of chemotherapy and photodynamic therapy provides a promising approach for enhanced tumor eradication by overcoming the limitations of each individual therapeutic modality. However, tumor is pathologically featured with extreme hypoxia together with the adaptable overexpression of anti-oxidants, such as glutathione (GSH), which greatly restricts the therapeutic efficiency. Here, a combinatorial strategy was designed to simultaneously relieve tumor hypoxia by self-oxygenation and reduce intracellular GSH level to sensitize chemo-photodynamic therapy. In our system, a novel multifunctional nanosystem based on MnO2-doped graphene oxide (GO) was developed to co-load cisplatin (CisPt) and a photosensitizer (Ce6). With MnO2 doping, the nanosystem was equipped with intelligent functionalities: (1) catalyzes the decomposition of H2O2 into oxygen to relieve the tumor hypoxia; (2) depletes GSH level in tumor cells, and (3) concomitantly generates Mn2+ to proceed Fenton-like reaction, all of which contribute to the enhanced anti-tumor efficacy. Meanwhile, the surface hyaluronic acid (HA) modification could facilitate the targeted delivery of the nanosystem into tumor cells, thereby resulting in amplified cellular toxicity, as well as tumor growth inhibition in nude mice model. This work sheds a new light on the development of intelligent nanosystems for synergistic combination therapy via regulating tumor microenvironment.
Key words:    Cisplatin    Nanoparticles    Photosensitizer    Tumor microenvironment    Oxygenation    GSH depletion    Nanozyme    Targeting   
Received: 2020-05-12     Revised: 2020-07-19
DOI: 10.1016/j.apsb.2020.07.021
Funds: This work was supported by Innovation-Driven Project of Central South University (No. 20170030010004, China), National Natural Science Foundation of China (No. 21804144, U1903125, China), Project of Hunan Science and Technology (No. 2020JJ8091, China), and Hunan Engineering Research Center for Optimization of Drug Formulation and Early Clinical Evaluation (No. 2015TP2005, China).
Corresponding author: Wenhu Zhou     Email:zhouwenhuyaoji@163.com
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Peng Liu
Xin Xie
Miao Liu
Shuo Hu
Jinsong Ding
Wenhu Zhou

References:
1. Nieboer P, de Vries EGE, Mulder NH, van der Graaf WTA. Relevance of high-dose chemotherapy in solid tumours. Canc Treat Rev 2005;3: 210-25.
2. Fan W, Yung B, Huang P, Chen X. Nanotechnology for multimodal synergistic cancer therapy. Chem Rev 2017;22:13566-638.
3. Shen B, Zhao K, Ma S, Yuan D, Bai Y. Topotecan-loaded mesoporous milica nanoparticles for reversing multi-drug resistance by synergetic chemoradiotherapy. Chem Asian J 2015;2:344-8.
4. Wu P, Wang XF, Wang ZD, Ma W, Guo JS, Chen JJ, et al. Lightactivatable prodrug and AIEgen copolymer nanoparticle for dual-drug monitoring and combination therapy. ACS Appl Mater Interfaces 2019;20:18691-700.
5. Voon SH, Kiew LV, Lee HB, Lim SH, Noordin MI, Kamkaew A, et al. In vivo studies of nanostructure-based photosensitizers for photodynamic cancer therapy. Small 2014;24:4993-5013.
6. Huang P, Lin J, Wang S, Zhou Z, Li Z, Wang Z, et al. Photosensitizerconjugated silica-coated gold nanoclusters for fluorescence imagingguided photodynamic therapy. Biomaterials 2013;19:4643-54.
7. Han K, Wang SB, Lei Q, Zhu JY, Zhang XZ. Ratiometric biosensor for aggregation-induced emission-guided precise photodynamic therapy. ACS Nano 2015;10:10268-77.
8. Liu P, Xie X, Shi X, Peng Y, Ding J, Zhou W. Oxygen-self-supplying and HIF-1a inhibiting core-shell nano-system for hypoxia-resistant photodynamic therapy. ACS Appl Mater Interfaces 2019;11: 48261-70.
9. Zhang J, Jiang CS, Longo JPF, Azevedo RB, Zhang H, Muehlmann LA. An updated overview on the development of new photosensitizers for anticancer photodynamic therapy. Acta Pharm Sin B 2018;2:137-46.
10. Liu K, Liu X, Zeng Q, Zhang Y, Tu L, Liu T, et al. Covalently assembled NIR nanoplatform for simultaneous fluorescence imaging and photodynamic therapy of cancer cells. ACS Nano 2012;5: 4054-62.
11. Wang Q, Dai YN, Xu JZ, Cai J, Niu XR, Zhang L, et al. All-in-one phototheranostics: single laser triggers NIR-II fluorescence/photoacoustic imaging guided photothermal/photodynamic/chemo combination therapy. Adv Funct Mater 2019;31:12.
12. Xiao Y, An FF, Chen J, Xiong S, Zhang XH. The impact of light irradiation timing on the efficacy of nanoformula-based photo/chemo combination therapy. J Mat Chem B 2018;22:3692-702.
13. Tang XL, Jing F, Lin BL, Cui S, Yu RT, Shen XD, et al. pH-responsive magnetic mesoporous silica-based nanoplatform for synergistic photodynamic therapy/chemotherapy. ACS Appl Mater Interfaces 2018;17:15001-11.
14. Liu R, Yu M, Yang X, Umeshappa CS, Hu C, Yu W, et al. Linear chimeric triblock molecules self-assembled micelles with controllably transformable property to enhance tumor retention for chemophotodynamic therapy of breast cancer. Adv Funct Mater 2019;23: 1808462.
15. Tian J, Xiao C, Huang B, Wang C, Zhang W. Janus macromolecular brushes for synergistic cascade-amplified photodynamic therapy and enhanced chemotherapy. Acta Biomater 2020;101:495-506.
16. Fang JF, Wang Q, Yang GJ, Xiao X, Li LC, Yu T. Albumin-MnO2 gated hollow mesoporous silica nanosystem for modulating tumor hypoxia and synergetic therapy of cervical carcinoma. Colloids Surf B Biointerfaces 2019;179:250-9.
17. Feng Y, Ding D, Sun W, Qiu Y, Luo L, Shi T, et al. Magnetic manganese oxide sweetgum-ball nanospheres with large mesopores regulate tumor microenvironments for enhanced tumor nanotheranostics. ACS Appl Mater Interfaces 2019;41:37461-70.
18. Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Canc 2004;6:437-47.
19. Liu L, Ruan Z, Li T, Yuan P, Yan L. Near infrared imaging-guided photodynamic therapy under an extremely low energy of light by galactose targeted amphiphilic polypeptide micelle encapsulating BODIPY-Br 2. Biomater Sci 2016;11:1638-45.
20. Dang J, He H, Chen D, Yin L. Manipulating tumor hypoxia toward enhanced photodynamic therapy (PDT). Biomater Sci 2017;8: 1500-11.
21. Kostenich G, Kimel S, Peled S, Orenstein A. Monitoring PDT-induced damage using spectrally resolved reflectance imaging of tissue oxygenation. Canc Lett 2005;2:169-75.
22. Sun Y, Zhao D, Wang G, Wang Y, Cao L, Sun J, et al. Recent progress of hypoxia-modulated multifunctional nanomedicines to enhance photodynamic therapy: opportunities, challenges, and future development. Acta Pharm Sin B 2020;10:1382-96.
23. Gao S, Wang G, Qin Z, Wang X, Zhao G, Ma Q, et al. Oxygengenerating hybrid nanoparticles to enhance fluorescent/photoacoustic/ultrasound imaging guided tumor photodynamic therapy. Biomaterials 2017;112:324-35.
24. Hu D, Chen L, Qu Y, Peng J, Chu B, Shi K, et al. Oxygen-generating hybrid polymeric nanoparticles with encapsulated doxorubicin and chlorin e6 for trimodal imaging-guided combined chemophotodynamic therapy. Theranostics 2018;6:1558-74.
25. Cheng YH, Cheng H, Jiang CX, Qiu XF, Wang KK, Huan W, et al. Perfluorocarbon nanoparticles enhance reactive oxygen levels and tumour growth inhibition in photodynamic therapy. Nat Commun 2015;1:1-8.
26. Chen X, Liu Y, Wen Y, Yu Q, Liu J, Zhao Y, et al. A photothermaltriggered nitric oxide nanogenerator combined with siRNA for precise therapy of osteoarthritis by suppressing macrophage inflammation. Nanoscale 2019;14:6693-709.
27. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;6:883-99.
28. Stowe DF, Camara AK. Mitochondrial reactive oxygen species production in excitable cells: modulators of mitochondrial and cell function. Antioxidants Redox Signal 2009;6:1373-414.
29. Kavćić N, Pegan K, Vandenabeele P, Turk B. Comparative study of the differential cell death protecting effect of various ROS scavengers. Biol Chem 2019;2:149-60.
30. Moloney JN, Cotter TG. ROS signalling in the biology of cancer. Semin Cell Dev Biol 2018;80:50-64.
31. Kiesslich T, Plaetzer K, Oberdanner CB, Berlanda J, Obermair FJ, Krammer B. Differential effects of glucose deprivation on the cellular sensitivity towards photodynamic treatment-based production of reactive oxygen species and apoptosis-induction. FEBS Lett 2005;1: 185-90.
32. Hall MD, Hambley TW. Platinum (IV) antitumour compounds: their bioinorganic chemistry. Coord Chem Rev 2002;1:49-67.
33. Váradi A, Sarkadi B. Multidrug resistance-associated proteins: export pumps for conjugates with glutathione, glucuronate or sulfate. Biofactors 2003;1:103-14.
34. Mellish K, Kelland L, Harrap K. In vitro platinum drug chemosensitivity of human cervical squamous cell carcinoma cell lines with intrinsic and acquired resistance to cisplatin. Brit J Cancer 1993;2: 240-50.
35. Surnar B, Sharma K, Jayakannan M. Coreeshell polymer nanoparticles for prevention of GSH drug detoxification and cisplatin delivery to breast cancer cells. Nanoscale 2015;42:17964-79.
36. Han Y, Yin W, Li J, Zhao H, Zha Z, Ke W, et al. Intracellular glutathione-depleting polymeric micelles for cisplatin prodrug delivery to overcome cisplatin resistance of cancers. J Control Release 2018;273:30-9.
37. Yang K, Feng L, Shi X, Liu Z. Nano-graphene in biomedicine: theranostic applications. Chem Soc Rev 2013;2:530-47.
38. Li J-L, Tang B, Yuan B, Sun L, Wang X-G. A review of optical imaging and therapy using nanosized graphene and graphene oxide. Biomaterials 2013;37:9519-34.
39. Liu J, Dong J, Zhang T, Peng Q. Graphene-based nanomaterials and their potentials in advanced drug delivery and cancer therapy. J Control Release 2018;286:64-73.
40. Luan X, Guan YY, Liu HJ, Lu Q, Zhao M, Sun D, et al. A tumor vascular-targeted interlocking trimodal nanosystem that induces and exploits hypoxia. Adv Sci 2018;8:1800034.
41. Liu J, Cui L, Losic D. Graphene and graphene oxide as new nanocarriers for drug delivery applications. Acta Biomater 2013;12: 9243-57.
42. Tian B, Wang C, Zhang S, Feng L, Liu Z. Photothermally enhanced photodynamic therapy delivered by nano-graphene oxide. ACS Nano 2011;9:7000-9.
43. Rong P, Yang K, Srivastan A, Kiesewetter DO, Yue X, Wang F, et al. Photosensitizer loaded nano-graphene for multimodality imaging guided tumor photodynamic therapy. Theranostics 2014;3: 229-39.
44. Liu P, Wang S, Liu X, Ding J, Zhou W. Platinated graphene oxide: a nanoplatform for efficient gene-chemo combination cancer therapy. Eur J Pharmaceut Sci 2018;121:319-29.
45. Dai Y, Wang B, Sun Z, Cheng J, Zhao H, Wu K, et al. Multifunctional theranostic liposomes loaded with a hypoxia-activated prodrug for cascade-activated tumor selective combination therapy. ACS Appl Mater Interfaces 2019;43:39410-23.
46. Wang M, Zhai Y, Ye H, Lv Q, Sun B, Luo C, et al. High co-loading capacity and stimuli-responsive release based on cascade reaction of self-destructive polymer for improved chemo-photodynamic therapy. ACS Nano 2019;6:7010-23.
47. Golla ED, Ayres GH. Spectrophotometric determination of platinum with o-phenylenediamine. Talanta 1973;2:199-210.
48. Ogura SI, Fujita Y, Kamachi T, Okura I. Preparation of chlorin e6-monoclonal antibody conjugate and its effect for photodynamic therapy. J Porphyr Phthalocyanines 2001;5:486-9.
49. Moore TL, Rodriguez-Lorenzo L, Hirsch V, Balog S, Urban D, Jud C, et al. Nanoparticle colloidal stability in cell culture media and impact on cellular interactions. Chem Soc Rev 2015;17: 6287-305.
50. Yang X, Yang Y, Gao F, Wei JJ, Qian CG, Sun MJ. Biomimetic hybrid nanozymes with self-supplied H+ and accelerated O2 generation for enhanced starvation and photodynamic therapy against hypoxic tumors. Nano Lett 2019;7:4334-42.
51. Zhang YH, Qiu WX, Zhang M, Zhang L, Zhang XZ. MnO2 motor: a prospective cancer-starving therapy promoter. ACS Appl Mater Interfaces 2018;17:15030-9.
52. Ju E, Dong K, Chen Z, Liu Z, Liu C, Huang Y, et al. Copper (II)e graphitic carbon nitride triggered synergy: improved ROS generation and reduced glutathione levels for enhanced photodynamic therapy. Angew Chem Int Ed 2016;38:11639-43.
53. Fan H, Yan G, Zhao Z, Hu X, Zhang W, Liu H, et al. A smart photosensitizeremanganese dioxide nanosystem for enhanced photodynamic therapy by reducing glutathione levels in cancer cells. Angew Chem Int Ed 2016;18:5477-82.
54. Wang XQ, Gao F, Zhang XZ. Initiator-loaded gold nanocages as a light-induced free-radical generator for cancer therapy. Angew Chem Int Ed 2017;31:9029-33.
55. Gibson D. The mechanism of action of platinum anticancer agentswhat do we really know about it?. Dalton Trans 2009;48:10681-9.
56. Lin LS, Song J, Song L, Ke K, Liu Y, Zhou Z, et al. Simultaneous fenton-like ion delivery and glutathione depletion by MnO2-based nanoagent to enhance chemodynamic therapy. Angew Chem Int Ed 2018;18:4902-6.
57. Wang Q, Tian S, Ning P. Degradation mechanism of methylene blue in a heterogeneous fenton-like reaction catalyzed by ferrocene. Ind Eng Chem Res 2014;2:643-9.
58. Hu C, Cun X, Ruan S, Liu R, Xiao W, Yang X, et al. Enzyme-triggered size shrink and laser-enhanced NO release nanoparticles for deep tumor penetration and combination therapy. Biomaterials 2018: 64-75.
59. Collignon J, Lousberg L, Schroeder H, Jerusalem G. Triple-negative breast cancer: treatment challenges and solutions. Breast Cancer 2016;8:93-107.
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