PCN-223 as a drug carrier for potential treatment of colorectal cancer

Nea Young Chun; Se-Na Kim; Youn Seo Choi; Young Bin Choy

Journal of Industrial and Engineering Chemistry, Vol.84, 290-296, April, 2020

DOI10.1016/j.jiec.2020.01.010 Export Citation

PCN-223 as a drug carrier for potential treatment of colorectal cancer

Nea Young Chun¹, Se-Na Kim², Youn Seo Choi¹, and Young Bin Choy^{1, 2, †}

¹Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul, 08826, Republic of Korea
²Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul, 03080, Republic of Korea

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Colorectal cancer is the second leading cause of cancer-related deaths worldwide. CRC is often treated with intravenous 5-fluorouracil (5FU). However, 5FU frequently shows low therapeutic efficacy and serious adverse events. Particulate drug carriers able to enhance intracellular delivery could be advantageous, since higher 5FU concentrations would be engulfed by cancer cells during a relatively short residence within the rectal space to improve local anti-cancer efficacy. Therefore, we propose a novel material based on a zirconium-based metal-organic framework (MOF), PCN-223, as a potential carrier of 5FU for rectal delivery of treatment for CRC. PCN-223 nanoparticles, prepared by the solvothermal method, exhibited a highly porous structure, whereby 79.4 μg/mg 5FU could be encapsulated and released in a sustained manner over 2 h in vitro. PCN-223 was internalized by the human colorectal cancer cell line, HCT-116, within 2 h, representing the period that rectally delivered particles reside within the rectum. Consequently, 5FU-loaded PCN-223 (5FU@PCN-223) treatment decreased the viability of HCT-116 cells compared with treatment with a bolus 5FU solution, suggesting improved drug efficacy over a short exposure time. Therefore, PCN-223 may be a promising carrier for rectal delivery of 5FU for treatment of colorectal cancer.

Keywords:5-Fluorouracil;Colorectal cancer;Metal-organic framework;Nanoparticle;Rectal delivery

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[2] Yassin AEB, Anwer MK, Mowafy HA, El-Bagory IM, Bayomi MA, Alsarra IA, Int. J. Med. Sci., 7, 398 (2010)

[3] Pan G, Bao YJ, Xu J, Liu T, Liu C, Qiu YY, Shi XJ, Yu H, Jia TT, Yuan X, Yuan ZT, Yin PH, Cao YJ, R.S.C. Adv., 6, 42109 (2016)

[4] Tummala S, Kuppusamy G, Satish Kumar MN, Praveen TK, Wadhwani A, Drug Deliv., 23, 2902 (2016)

[5] Pan G, Jia TT, Huan QX, Qiu YY, Xu J, Yin PH, Liu T, Colloids Surf. B: Biointerfaces, 159, 375 (2017)

[6] Varma VNSK, Shivakumar HG, Fathima SJ, Radha V, Khanum F, R.S.C. Adv., 6, 105495 (2016)

[7] Arias JL, Molecules, 13, 2340 (2008)

[8] Tummala S, Sumar Kumar MN, Prakash A, Saudi Pharm. J., 23, 308 (2015)

[9] Wang LL, Huang S, Guo HH, Han YX, Zheng WS, Jiang JD, Drug Des. Devel. Ther., 10, 2855 (2016)

[10] Melo M, Nunes R, Sarmento B, das Neves J, Mater. Today Chem., 10, 128 (2018)

[11] Nunes R, Araujo F, Tavares J, Sarmento B, das Neves J, Eur. J. Pharm. Biopharm., 130, 200 (2018)

[12] Li H, Eddaoudi M, O’Keeffe M, Yaghi OM, Nature, 402, 276 (1999)

[13] Yaghi OM, O’Keeffe M, Ockwig NW, Chae HK, Eddaoudi M, Kim J, Nature, 423, 705 (2003)

[14] Li X, Lachmanski L, Safi S, Sene S, Serre C, Greneche JM, Zhang J, Gref R, Sci. Rep., 7, 13142 (2017)

[15] Lan G, Ni K, Lin W, Coord. Chem. Rev., 379, 65 (2019)

[16] Xu RY, Wang YF, Duan XP, Lu KD, Micheroni D, Hu AG, Lin WB, J. Am. Chem. Soc., 138(7), 2158 (2016)

[17] Li JR, Kuppler RJ, Zhou HC, Chem. Soc. Rev., 38, 1477 (2009)

[18] Schmidt BVKJ, Macromol. Rapid. Comm., 41 (2020)

[19] Wu MX, Yang YW, Adv. Mater., 29 (2017)

[20] Bai Y, Dou Y, Xie LH, Rutledge W, Li JR, Zhou HC, Chem. Soc. Rev., 45, 2327 (2016)

[21] Feng D, Gu Z, Chen Y, Park J, Wei Z, Sun Y, Bosch M, Yuan S, Zhou H, J. Am. Ceram. Soc., 136, 17714 (2014)

[22] Kelty ML, Morris W, Gallagher AT, Anderson JS, Brown KA, Mirkin CA, Harris TD, Chem. Commun., 52, 7854 (2016)

[23] Jeong H, Rho J, Shin JY, Lee DY, Hwang T, Kim KJ, Biomed. Eng. Lett., 8, 267 (2018)

[24] Li L, Shen S, Lin R, Bai Y, Liu H, Chem. Commun., 53, 9986 (2017)

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[29] Yang J, Chen XJ, Li YS, Zhuang QX, Liu PF, Gu JL, Chem. Mater., 29, 4580 (2017)

[30] Al-Thawabeia RA, Hodali HA, J. Chem., 2015, 403597 (2015)

[31] Cunha D, Yahia MB, Hall S, Miller SR, Chevreau H, Elkaim E, Maurin G, Horcajada P, Serre C, Chem. Mater., 25, 2767 (2013)

[32] Singh S, Kotla NG, Tomar S, Maddiboyina B, Webster TJ, Sharma D, Sunnapu O, Int. J. Nanomed., 10, 7175 (2015)

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[34] Imoto M, Azuma H, Yamamoto I, Otagiri M, Imai T, J. Drug. Deliv. Sci. Tec., 19, 37 (2009)

[35] Ashwanikumar N, Kumar NA, Nair SA, Kumar GSV, Int. J. Nanomed., 7, 5769 (2012)

[36] Shafik A, El-Sibai O, El-Gohary H, Khalid AM, Khalil A, Tech. Coloprotocol., 3, 19 (1999)

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[39] De Conno F, Ripamonti C, Saita L, MacEachern T, Hanson J, Bruera E, J. Clin. Oncol., 13, 1004 (1995)