Skip to main content

Advertisement

SpringerLink
Log in

Stealth Polymer-Coated Graphene Oxide Decorated Mesoporous Titania Nanoplatforms for In Vivo Chemo-Photodynamic Cancer Therapy

  • RESEARCH PAPER
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

The goal of this study was to develop chemotherapeutic drug-loaded photoactivable stealth polymer-coated silica based- mesoporous titania nanoplatforms for enhanced antitumor activity.

Methods

Both in vitro and in vivo models of solvothermal treated photoactivable nanoplatforms were evaluated for efficient chemo-photothermal activity. A versatile nanocomposite that combined silica based- mesoporous titania nanocarriers (S-MTN) with the promising photoactivable agent, graphene oxide (G) modified with a stealth polymer (P) was fabricated to deliver chemotherapeutic agent, imatinib (I), (referred as S-MTN@IG-P) for near-infrared (NIR)-triggered drug delivery and enhanced chemo-photothermal therapy.

Results

The fabricated S-MTN@IG-P nanoplatform showed higher drug loading (~20%) and increased drug release (~60%) in response to light in acidic condition (pH 5.0). As prepared nanoplatform significantly converted NIR light into thermal energy (43.2°C) to produce reactive oxygen species (ROS). The pronounced cytotoxic effect was seen in both colon cancer cells (HCT-116 and HT-29) that was mediated through the chemotherapeutic effect of imatinib and the photothermal and ROS generation effects of graphene oxide. In vivo study also showed that S-MTN@IG-P could significantly accumulate into the tumor area and suppress the tumor growth under NIR irradiation without any biocompatibility issues.

Conclusion

Cumulatively, the above results showed promising effects of S-MTN@IG-P for effective chemo-phototherapy of colon cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Liu Y, Bhattarai P, Dai Z, Chen X. Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer. Chem Soc Rev. 2019;48:2053–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Gautam M, Poudel K, Yong CS, Kim JO. Prussian blue nanoparticles: synthesis, surface modification, and application in cancer treatment. Int J Pharm. 2018;549:31–49.

    Article  CAS  PubMed  Google Scholar 

  3. Gai S, Yang G, Yang P, He F, Lin J, Jin D, Xing B. Recent advances in functional nanomaterials for light–triggered cancer therapy. Nano Today. 2018;19:146–87.

    Article  CAS  Google Scholar 

  4. Ye H, Wang K, Wang M, Liu R, Song H, Li N, Lu Q, Zhang W, Du Y, Yang W, Zhong L, Wang Y, Yu B, Wang H, Kan Q, Zhang H, Wang Y, He Z, Sun J. Bioinspired nanoplatelets for chemo-photothermal therapy of breast cancer metastasis inhibition. Biomaterials. 2019;206:1–12.

    Article  CAS  PubMed  Google Scholar 

  5. 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;34:9519–34.

    Article  CAS  PubMed  Google Scholar 

  6. Yin M, Ju E, Chen Z, Li Z, Ren J, Qu X. Upconverting nanoparticles with a Mesoporous TiO2 Shell for near-infrared-triggered drug delivery and synergistic targeted Cancer therapy. Chem Eur J. 2014;20:14012–7.

    Article  CAS  PubMed  Google Scholar 

  7. Kiew SF, Kiew LV, Lee HB, Imae T, Chung LY. Assessing biocompatibility of graphene oxide-based nanocarriers: a review. J Control Release. 2016;226:217–28.

    Article  CAS  PubMed  Google Scholar 

  8. J.B. Vines, J.-H. Yoon, N.-E. Ryu, D.-J. Lim, and H. Park. Gold Nanoparticles for Photothermal Cancer Therapy. Frontiers in Chemistry. 7: (2019).

  9. Poudel K, Gautam M, Jin SG, Choi H-G, Yong CS, Kim JO. Copper sulfide: an emerging adaptable nanoplatform in cancer theranostics. Int J Pharm. 2019;562:135–50.

    Article  CAS  PubMed  Google Scholar 

  10. Wang S, Zhang Q, Yang P, Yu X, Huang L-Y, Shen S, Cai S. Manganese oxide-coated carbon nanotubes as dual-modality lymph mapping agents for Photothermal therapy of tumor metastasis. ACS Appl Mater Interfaces. 2016;8:3736–43.

    Article  CAS  PubMed  Google Scholar 

  11. Jain PK, Huang X, El-Sayed IH, El-Sayed MA. Noble metals on the Nanoscale: optical and Photothermal properties and some applications in imaging, sensing, biology, and medicine. Acc Chem Res. 2008;41:1578–86.

    Article  CAS  PubMed  Google Scholar 

  12. Jung HS, Verwilst P, Sharma A, Shin J, Sessler JL, Kim JS. Organic molecule-based photothermal agents: an expanding photothermal therapy universe. Chem Soc Rev. 2018;47:2280–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Cheng L, Wang C, Feng L, Yang K, Liu Z. Functional nanomaterials for phototherapies of Cancer. Chem Rev. 2014;114:10869–939.

    Article  CAS  PubMed  Google Scholar 

  14. Shen H, Zhang L, Liu M, Zhang Z. Biomedical applications of graphene. Theranostics. 2012;2:283–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gautam M, Thapa RK, Poudel BK, Gupta B, Ruttala HB, Nguyen HT, Soe ZC, Ou W, Poudel K, Choi H-G, Ku SK, Yong CS, Kim JO. Aerosol technique-based carbon-encapsulated hollow mesoporous silica nanoparticles for synergistic chemo-photothermal therapy. Acta Biomater. 2019;88:448–61.

    Article  CAS  PubMed  Google Scholar 

  16. Kango S, Kalia S, Celli A, Njuguna J, Habibi Y, Kumar R. Surface modification of inorganic nanoparticles for development of organic–inorganic nanocomposites—a review. Prog Polym Sci. 2013;38:1232–61.

    Article  CAS  Google Scholar 

  17. Li L, Li X, Duan H, Wang X, Luo C. Removal of Congo red by magnetic mesoporous titanium dioxide–graphene oxide core–shell microspheres for water purification. Dalton Trans. 2014;43:8431–8.

    Article  CAS  PubMed  Google Scholar 

  18. Song Y-Y, Schmidt-Stein F, Bauer S, Schmuki P. Amphiphilic TiO2 nanotube arrays: an actively controllable drug delivery system. J Am Chem Soc. 2009;131:4230–2.

    Article  CAS  PubMed  Google Scholar 

  19. Rozhkova EA, Ulasov I, Lai B, Dimitrijevic NM, Lesniak MS, Rajh T. A high-performance Nanobio Photocatalyst for targeted brain cancer therapy. Nano Lett. 2009;9:3337–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Szaciłowski K, Macyk W, Drzewiecka-Matuszek A, Brindell M, Stochel G. Bioinorganic photochemistry: Frontiers and mechanisms. Chem Rev. 2005;105:2647–94.

    Article  PubMed  CAS  Google Scholar 

  21. Lim JH, Kim DE, Kim E-J, Ahrberg CD, Chung BG. Functional Graphene oxide-based Nanosheets for Photothermal therapy. Macromol Res. 2018;26:557–65.

    Article  CAS  Google Scholar 

  22. Ganesan D, Samikannu A, Muthaiah C, Muniyan Ramasamy K, Kannaiyan D. Synthesis and characterization of CdS nanoparticle anchored silica-Titania mixed oxide mesoporous particles: efficient photocatalyst for discoloration of textile effluent. Int J Nano Dimen. 2019;10:272–80.

    Google Scholar 

  23. He Y, Wan J, Yang Y, Yuan P, Yang C, Wang Z, Zhang L. Multifunctional Polypyrrole-coated Mesoporous TiO2 Nanocomposites for Photothermal, Sonodynamic, and chemotherapeutic treatments and dual-modal ultrasound/Photoacoustic imaging of tumors. Adv Healthcare Mater. 2019;8:1801254.

    Article  CAS  Google Scholar 

  24. Masoudi M, Mashreghi M, Goharshadi E, Meshkini A. Multifunctional fluorescent titania nanoparticles: green preparation and applications as antibacterial and cancer theranostic agents. Artif Cells Nanomed Biotechnol. 2018;46:248–59.

    Article  CAS  PubMed  Google Scholar 

  25. Feng L, Yang X, Shi X, Tan X, Peng R, Wang J, Liu Z. Polyethylene glycol and Polyethylenimine dual-functionalized Nano-Graphene oxide for Photothermally enhanced gene delivery. Small. 2013;9:1989–97.

    Article  CAS  PubMed  Google Scholar 

  26. Cheng H, Gadora K, Wang Z, Zhang H, Jiang W, Chen X, Han G, Jin Y, Zhou J, Jiang L, Ding Y. Functionalized nanographene oxide in biomedicine applications: bioinspired surface modifications, multidrug shielding, and site-specific trafficking. Drug Discov Today. 2019;24:749–62.

    Article  CAS  PubMed  Google Scholar 

  27. Wen H, Dong C, Dong H, Shen A, Xia W, Cai X, Song Y, Li X, Li Y, Shi D. Engineered redox-responsive PEG detachment mechanism in PEGylated nano-graphene oxide for intracellular drug delivery. Small. 2012;8:760–9.

    Article  CAS  PubMed  Google Scholar 

  28. Tran P, Lee S-E, Kim D-H, Pyo Y-C, Park J-S. Recent advances of nanotechnology for the delivery of anticancer drugs for breast cancer treatment. J Pharm Investig. 2020;50:261–70.

    Article  CAS  Google Scholar 

  29. Palai PK, Mondal A, Chakraborti CK, Banerjee I, Pal K. Green synthesized amino-PEGylated silver decorated graphene nanoplatform as a tumor-targeted controlled drug delivery system. SN Appl Sci. 2019;1:269.

    Article  CAS  Google Scholar 

  30. Yang K, Zhang S, Zhang G, Sun X, Lee S-T, Liu Z. Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett. 2010;10:3318–23.

    Article  CAS  PubMed  Google Scholar 

  31. Phung DC, Nguyen HT, Phuong Tran TT, Jin SG, Yong CS, Truong DH, Tran TH, Kim JO. Combined hyperthermia and chemotherapy as a synergistic anticancer treatment. J Pharm Invest. 2019;49:519–26.

    Article  Google Scholar 

  32. Miao W, Shim G, Lee S, Lee S, Choe YS, Oh Y-K. Safety and tumor tissue accumulation of pegylated graphene oxide nanosheets for co-delivery of anticancer drug and photosensitizer. Biomaterials. 2013;34:3402–10.

    Article  CAS  PubMed  Google Scholar 

  33. Wu KCW, Yamauchi Y, Hong C-Y, Yang Y-H, Liang Y-H, Funatsu T, Tsunoda M. Biocompatible, surface functionalized mesoporous titania nanoparticles for intracellular imaging and anticancer drug delivery. Chem Commun. 2011;47:5232–4.

    Article  CAS  Google Scholar 

  34. Meier M, Ungerer J, Klinge M, Nirschl H. Synthesis of nanometric silica particles via a modified Stöber synthesis route. Colloids Surf A Physicochem Eng Asp. 2018;538:559–64.

    Article  CAS  Google Scholar 

  35. Gupta B, Ruttala HB, Poudel BK, Pathak S, Regmi S, Gautam M, Poudel K, Sung MH, Ou W, Jin SG, Jeong J-H, Ku SK, Choi H-G, Yong CS, Kim JO. Polyamino acid layer-by-layer (LbL) constructed silica-supported mesoporous titania nanocarriers for stimuli-responsive delivery of microRNA 708 and paclitaxel for combined chemotherapy. ACS Appl Mater Interfaces. 2018;10:24392–405.

    Article  CAS  PubMed  Google Scholar 

  36. Knöfel C, Martin C, Hornebecq V, Llewellyn PL. Study of carbon dioxide adsorption on Mesoporous Aminopropylsilane-functionalized silica and Titania combining Microcalorimetry and in situ infrared spectroscopy. J Phys Chem C. 2009;113:21726–34.

    Article  CAS  Google Scholar 

  37. Gautam M, Ku SK, Kim JO, Byeon JH. A scalable on-demand platform to assemble base nanocarriers for combination cancer therapy. Nanoscale. 2018;10:11737–44.

    Article  CAS  PubMed  Google Scholar 

  38. Atlihan-Gundogdu E, Ilem-Ozdemir D, Ekinci M, Ozgenc E, Demir ES, Sánchez-Dengra B, González-Alvárez I. Recent developments in cancer therapy and diagnosis. J Pharm Investig. 2020;50:349–61.

    Article  Google Scholar 

  39. Acharyaand S, Sahoo SK. PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev. 2011;63:170–83.

    Article  CAS  Google Scholar 

  40. Chen R, Wang J, Qian C, Ji Y, Zhu C, Wu L, Li W, Bi X, Wang Y, Cao G, Chen Z. From Nanofibers to Nanorods: nanostructure of peptide-drug conjugates regulated by polypeptide-PEG derivative and enhanced antitumor effect. Adv Funct Mater. 2019;29:1806058.

    Article  CAS  Google Scholar 

  41. Behnam MA, Emami F, Sobhani Z, Dehghanian AR. The application of titanium dioxide (TiO(2)) nanoparticles in the photo-thermal therapy of melanoma cancer model. Iran J Basic Med Sci. 2018;21:1133–9.

    PubMed  PubMed Central  Google Scholar 

  42. Zhao J, Milanova M, Warmoeskerken MMCG, Dutschk V. Surface modification of TiO2 nanoparticles with silane coupling agents. Colloids Surf A Physicochem Eng Asp. 2012;413:273–9.

    Article  CAS  Google Scholar 

  43. Kim H-i, Moon G-h, Monllor-Satoca D, Park Y, Choi W. Solar photoconversion using graphene/TiO2 composites: nanographene Shell on TiO2 Core versus TiO2 nanoparticles on graphene sheet. J Phys Chem C. 2012;116:1535–43.

    Article  CAS  Google Scholar 

  44. Kamali M, Dinarvand R, Maleki H, Arzani H, Mahdaviani P, Nekounam H, Adabi M, Khosravani M. Preparation of imatinib base loaded human serum albumin for application in the treatment of glioblastoma. RSC Adv. 2015;5:62214–9.

    Article  CAS  Google Scholar 

  45. Charmi J, Nosrati H, Mostafavi Amjad J, Mohammadkhani R, Danafar H. Polyethylene glycol (PEG) decorated graphene oxide nanosheets for controlled release curcumin delivery. Heliyon. 2019;5:e01466.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Raja A, Selvakumar K, Rajasekaran P, Arunpandian M, Ashokkumar S, Kaviyarasu K, Asath Bahadur S, Swaminathan M. Visible active reduced graphene oxide loaded titania for photodecomposition of ciprofloxacin and its antibacterial activity. Colloids Surf A Physicochem Eng Asp. 2019;564:23–30.

    Article  CAS  Google Scholar 

  47. El-Shafai N, El-Khouly ME, El-Kemary M, Ramadan M, Eldesoukey I, Masoud M. Graphene oxide decorated with zinc oxide nanoflower, silver and titanium dioxide nanoparticles: fabrication, characterization, DNA interaction, and antibacterial activity. RSC Adv. 2019;9:3704–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Moand R, Gu Z. Tumor microenvironment and intracellular signal-activated nanomaterials for anticancer drug delivery. Mater Today. 2016;19:274–83.

    Article  CAS  Google Scholar 

  49. Devanand Venkatasubbu G, Ramasamy S, Ramakrishnan V, Kumar J. Folate targeted PEGylated titanium dioxide nanoparticles as a nanocarrier for targeted paclitaxel drug delivery. Adv Powder Technol. 2013;24:947–54.

    Article  CAS  Google Scholar 

  50. Du Y, Ren W, Li Y, Zhang Q, Zeng L, Chi C, Wu A, Tian J. The enhanced chemotherapeutic effects of doxorubicin loaded PEG coated TiO2 nanocarriers in an orthotopic breast tumor bearing mouse model. J Mater Chem B. 2015;3:1518–28.

    Article  CAS  PubMed  Google Scholar 

  51. Shim G, Miao W, Ko S, Park GT, Kim JY, Kim MG, Kim YB, Oh YK. Immune-camouflaged graphene oxide nanosheets for negative regulation of phagocytosis by macrophages. J Mater Chem B. 2017;5:6666–75.

    Article  CAS  PubMed  Google Scholar 

  52. Kolemen S, Ozdemir T, Lee D, Kim GM, Karatas T, Yoon J, Akkaya EU. Remote-controlled release of singlet oxygen by the Plasmonic heating of Endoperoxide-modified gold Nanorods: towards a paradigm change in photodynamic therapy. Angew Chem Int Ed. 2016;55:3606–10.

    Article  CAS  Google Scholar 

  53. Wang L, Yu D, Dai R, Fu D, Li W, Guo Z, Cui C, Xu J, Shen S, Ma K. PEGylated doxorubicin cloaked nano-graphene oxide for dual-responsive photochemical therapy. Int J Pharm. 2019;557:66–73.

    Article  CAS  PubMed  Google Scholar 

  54. Ding L, Li J, Huang R, Liu Z, Li C, Yao S, Wang J, Qi D, Li N, Pi J. Salvianolic acid B protects against myocardial damage caused by nanocarrier TiO(2); and synergistic anti-breast carcinoma effect with curcumin via codelivery system of folic acid-targeted and polyethylene glycol-modified TiO(2) nanoparticles. Int J Nanomedicine. 2016;11:5709–27.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Zhang W, Guo Z, Huang D, Liu Z, Guo X, Zhong H. Synergistic effect of chemo-photothermal therapy using PEGylated graphene oxide. Biomaterials. 2011;32:8555–61.

    Article  CAS  PubMed  Google Scholar 

  56. Jeon G, Ko YT. Enhanced photodyamic therapy via photosensitizer-loaded nanoparticles for cancer treatment. J Pharm Investig. 2019;49:1–8.

    Article  CAS  Google Scholar 

  57. Hong SH, Choi Y. Mesoporous silica-based nanoplatforms for the delivery of photodynamic therapy agents. J Pharm Investig. 2018;48:3–17.

    Article  CAS  PubMed  Google Scholar 

  58. Le Q-V, Choi J, Oh Y-K. Nano delivery systems and cancer immunotherapy. J Pharm Investig. 2018;48:527–39.

    Article  CAS  Google Scholar 

  59. Liao K-H, Lin Y-S, Macosko CW, Haynes CL. Cytotoxicity of graphene oxide and Graphene in human erythrocytes and skin fibroblasts. ACS Appl Mater Interfaces. 2011;3:2607–15.

    Article  CAS  PubMed  Google Scholar 

  60. Abstiens K, Maslanka Figueroa S, Gregoritza M, Goepferich AM. Interaction of functionalized nanoparticles with serum proteins and its impact on colloidal stability and cargo leaching. Soft Matter. 2019;15:709–20.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research study was supported by Yeungnam University in 2020.

Author information

Authors and Affiliations

  1. College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea

    Milan Gautam, Biki Gupta, Zar Chi Soe, Kishwor Poudel, Srijan Maharjan, Jee-Heon Jeong, Chul Soon Yong & Jong Oh Kim

  2. College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, Republic of Korea

    Han-Gon Choi

  3. College of Korean Medicine, Daegu Haany University, Gyeongsan, 38610, Republic of Korea

    Sae Kwang Ku

Authors
  1. Milan Gautam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Biki Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zar Chi Soe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kishwor Poudel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Srijan Maharjan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jee-Heon Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Han-Gon Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sae Kwang Ku
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chul Soon Yong
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jong Oh Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Chul Soon Yong or Jong Oh Kim.

Ethics declarations

Conflict of Interest

There are no conflicts to declare.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 7902 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gautam, M., Gupta, B., Soe, Z.C. et al. Stealth Polymer-Coated Graphene Oxide Decorated Mesoporous Titania Nanoplatforms for In Vivo Chemo-Photodynamic Cancer Therapy. Pharm Res 37, 162 (2020). https://doi.org/10.1007/s11095-020-02900-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11095-020-02900-1

Key Words

Search

Navigation