Antibreast Cancer Activity of Aspirin-Conjugated Chalcone Polymeric Micelles

Do Young Lee; Kang Pa Lee; Suji Beak; Ji Su Park; Young Jin Kim; Kil-Nam Kim; Song-Rae Kim; Myeong Sik Yoon

Macromolecular Research, Vol.29, No.1, 105-110, January, 2021

DOI10.1007/s13233-021-9010-y Export Citation

Antibreast Cancer Activity of Aspirin-Conjugated Chalcone Polymeric Micelles

Do Young Lee¹, Kang Pa Lee², Suji Beak², Ji Su Park¹, Young Jin Kim¹, Kil-Nam Kim³, Song-Rae Kim³, and Myeong Sik Yoon^{1, 4, †}

¹Department of Pharmaceutical Engineering, Hoseo University, Asan, Chungnam 31499, Korea
²Research & Development Center, UMUST R&D Corporation, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea
³Chuncheon Center, Korea Basic Science Institute (KBSI), Chuncheon 24341, Korea
⁴The Research Institute for Basic Sciences, Hoseo University, Asan, Chungnam 31499, Korea

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Chalcones are hydrophobic polyphenols with poor aqueous solubility. In this study, we prepared a new aspirin-conjugated chalcone derivative-loaded nanoparticle (AS-DK143-loaded NP) using mPEG-PLA co-polymer which, in an aqueous environment, spontaneously forms a micellar formulation with an average particle size of 22.55 nm. Exposure to varying concentrations of AS-DK143 NP significantly diminished the cell viability of 4T1 cells in a concentration-dependent manner. In tumor regression and biodistribution studies in 4T1-luc cell bearing mice, AS-DK143 NPs were shown to selectively target cancer cells and significantly reduce tumor size. These properties suggest anti-cancer efficacy, combined with low toxicity to healthy tissues, indicating a potential role as a safer alternative to currently available chemotherapy agents.

Keywords:chalcone;breast cancer;drug delivery system;polymeric micelles;4T1 cells

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[2] Youlden DR, Cramb SM, Yip CH, Baade PD, Cancer Biol. Med., 11, 101 (2014)

[3] Lorizio W, Wu AH, Beattie MS, Rugo H, Tchu S, Kerlikowske K, Ziv E, Breast Cancer Res. Treat., 132, 1107 (2012)

[4] Chen X, Lowe M, Herliczek T, Hall MJ, Danes C, Lawrence DA, Keyomarsi K, J. Natl. Cancer Inst., 92, 1999 (2000)

[5] Senapati S, Mahanta AK, Kumar S, Maiti P, Signal Transduct. Target. Ther., 3, 7 (2018)

[6] Lee DH, Jung YJ, Koh D, Lim Y, Lee YH, Shin SY, Cancer Lett., 372, 1 (2016)

[7] Kalepu S, Nekkanti V, Acta Pharm. Sin. B, 5, 442 (2015)

[8] Undas A, Brummel-Ziedins KE, Mann KG, Blood, 109, 2285 (2007)

[9] Boutaud, Sosa IR, Amin T, Oram D, Adler D, Hwang HS, Crews BC, et al., Cancer Prev. Res., 9, 855 (2016)

[10] Sostres OC, Gargallo CJ, Lanas A, World J. Gastrointest. Pharmacol. Ther., 5, 40 (2014)

[11] Kim YI, Kim SY, Kim JH, Lee JH, Kim YW, Ryu KW, Park JH, Choi IJ, Cancer Res. Treat., 48, 798 (2016)

[12] Hao W, Shen Y, Feng M, Wang H, Lin M, Fang Y, Tan L, J. Thorac. Dis., 10, 2490 (2018)

[13] Shin SY, Lee JM, Lee MS, Koh DS, Jung HR, Lim YH, Lee YH, Clin. Cancer Res., 20, 4302 (2014)

[14] Bae YS, Oh H, Rhee SG, Yoo YD, Mol. Cells, 32, 491 (2011)

[15] Aggarwal V, Tuli HS, Varol A, Thakral F, Yerer MB, Sak K, Varol M, Jain A, Khan MA, Sethi G, Biomolecules, 9, 735 (2019)

[16] Mates JM, Sanchez-Jimenez FM, Int. J. Biochem. Cell Biol., 32, 157 (2000)

[17] Zang YQ, Feng YY, Luo YH, Zhai YQ, Ju XY, Feng YC, Sheng YN, Wang JR, Yu CQ, Jin CH, Mol. Med. Rep., 20, 4576 (2019)

[18] Zhu H, Tang L, Zhang C, Wei B, Yang P, He D, Zheng L, Zhang Y, Front. Pharmacol., 10, 1341 (2019)

[19] Lavis LD, ACS Chem. Biol., 3, 203 (2008)

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[21] Fisusi FA, Akala EO, Pharm. Nanotechnol., 7, 3 (2019)

[22] Xu W, Ling P, Zhang P, J. Drug Deliv., 2013, 340315 (2013)

[23] Kim YJ, Lee KP, Lee DY, Kim YT, Koh DS, Lim YH, Yoon MS, Macromol. Res., 27(1), 48 (2019)