Synthesis of Multifunctional Organic Nanoparticles Combining Photodynamic Therapy and Chemotherapeutic Drug Release

Fazli Sozmen; Merve Kucukoflaz; Mustafa Ergul; Zeynep Deniz Sahin Inan; Yasemin Bozkurt; Dilsad Taydas

Macromolecular Research, Vol.30, No.1, 61-69, January, 2022

DOI10.1007/s13233-022-0021-0 Export Citation

Synthesis of Multifunctional Organic Nanoparticles Combining Photodynamic Therapy and Chemotherapeutic Drug Release

Fazli Sozmen^†, Merve Kucukoflaz, Mustafa Ergul¹, Zeynep Deniz Sahin Inan², Yasemin Bozkurt, and Dilsad Taydas

Nanotechnology Engineering Department, Faculty of Engineering, Sivas Cumhuriyet University, 58140, Sivas, Turkey
¹Biochemistry Department, Faculty of Pharmacy, Sivas Cumhuriyet University, 58140, Sivas, Turkey
²Histology and Embryology Department, Faculty of Medicine, Sivas Cumhuriyet University, 58140, Sivas, Turkey

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Cancer is a group of diseases that are caused by uncontrolled proliferation of cells in various parts of the body and it is one of the most studied diseases worldwide. Photodynamic therapy (PDT) is a treatment that uses photosensitizers called photosensitizing agents in addition to light to kill cancer cells. Photosensitizers work only after they have been activated by certain types of light. PDT contains three basic components, these are a photosensitizer, visible light and molecular oxygen (3O2). The efficiency of the therapeutic action is directly related to the property of the photosensitizer. In this study, chitosan and BODIPY based nanoparticles that were capable of carrying out drug delivery and producing singlet oxygen (1O2) were synthesized for the first time. For this purpose, organic nanoparticles showed PDT feature were synthesized via the formation of ionic complexes formed with opposite charged ionic interactions between the synthesized BODIPY derivative (PDT agent) and chitosan hydrochloride at appropriate pH (pH=6). Later, during the formation of this ionic complex, a chemotherapeutic model drug (Doxorubicin) was added to the medium and chemotherapeutic drug-loaded chitosan and BODIPY-based nanoparticles were synthesized. Finally, while drug-free (Y1-Chitosan nanoparticles) and drug-loaded organic nanoparticles (Y1-Chitosan-Dox nanoparticles) showed very good PDT properties, they were found to be effective on MCF7 cancer cells and less toxic to L929 cells.

Keywords:photodynamic therapy;chitosan;BODIPY;doxorubicin;drug release

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[2] Lv PP, Ma YF, Yu R, Yue H, Ni DZ, Wei W, Ma GH, Mol. Pharm., 9, 1736 (2012)

[3] Guo Y, Chu M, Tan S, Zhao S, Liu h, Otieno BO, Yang X, Xu C, Zhang Z, Mol. Pharm., 11, 59 (2014)

[4] Gottesman MM, Fojo T, Bates SE, Nat. Rev. Cancer, 2, 48 (2002)

[5] Patel JK, Jivani NP, Int. J. Pharm. Sci. Nanotechnol., 2, 519 (2009)

[6] Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE, J. Control. Release, 70, 1 (2001)

[7] Kamat V, Marathe I, Ghormade V, Bodas D, Paknikar K, ACS Appl. Mater. Interfaces, 7, 22839 (2015)

[8] Wang JJ, Zeng ZW, Xiao RZ, Xie T, Zhou GL, Zhan XR, Wang SL, Int. J. Nanomedicine, 6, 765 (2011)

[9] Keawchaoon L, Yoksan R, Colloids Surf. B: Biointerfaces, 84, 163 (2011)

[10] Pan Y, Li Y, Zhao H, Zheng J, Xu H, Int. J. Pharm., 249, 139 (2002)

[11] Sung H, Sonaje K, Liao Z, Hsu L, Chuang E, Accounts Chem. Res., 45, 619 (2012)

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[13] Goethals EC, Elbaz A, Lopata AL, Bhargava SK, Bansal V, Langmuir, 29(2), 658 (2013)

[14] Aljabali AAA, Shukla S, Lomonossoff GP, Steinmetz NF, Evans DJ, Molecular Pharmaceutics (2013).

[15] Shi J, Xiao Z, Kamaly N, Farokhzad OC, Accounts Chem. Res., 44, 1123 (2011)

[16] Yu MK, Park J, Jon S, Theranostics, 2, 3 (2012)

[17] Coskun A, Akkaya EU, J. Am. Chem. Soc., 127(30), 10464 (2005)

[18] Arbeloa TL, Arbeloa FL, Arbeloa IL, Garcia-Moreno I, Costela A, Sastre R, Amat-Guerri F, Chem. Phys. Lett., 299, 315 (1999)

[19] Erten-Ela S, Yilmaz MD, Icli B, Dede Y, Icli S, Akkaya EU, Org. Lett., 10, 3299 (2008)

[20] Bozdemir OA, Yilmaz MD, Buyukcakir O, Siemiarczuk A, Tutas M, Akkaya EU, New J. Chem., 34, 151 (2010)

[21] Loudet A, Burgess K, Chem. Rev., 107(11), 4891 (2007)

[22] Isik M, Ozdemir T, Turan IS, Kolemen S, Akkaya EU, Org. Lett., 15, 216 (2013)

[23] Cui W, Lu XM, Cui K, Wu J, Wei Y, Let QH, Langmuir, 27(13), 8384 (2011)

[24] Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S, Nature, 391(6662), 43 (1998)

[25] Walsh JG, Cullen SP, Sheridan C, Luthi AU, Gerner C, Martin SJ, Proc. Natl. Acad. Sci. U.S.A., 105, 12815 (2008)