Anticancer effect of intracellular-delivered paclitaxel using novel pH-sensitive LMWSC-PCL di-block copolymer micelles

Gyeong-Won Jeong; Woong-Gil Hong; Jun-Hyuk Anh; You-Jin Jeon; Suk Soon Choi; Tae-Il Son; Sang Chai Kim; Young-Il Jeong; Jae-Woon Nah

Journal of Industrial and Engineering Chemistry, Vol.70, 136-144, February, 2019

DOI10.1016/j.jiec.2018.09.049 Export Citation

Anticancer effect of intracellular-delivered paclitaxel using novel pH-sensitive LMWSC-PCL di-block copolymer micelles

Gyeong-Won Jeong, Woong-Gil Hong, Jun-Hyuk Anh, You-Jin Jeon¹, Suk Soon Choi², Tae-Il Son³, Sang Chai Kim⁴, Young-Il Jeong^{1, †}, and Jae-Woon Nah^†

Department of Polymer Science and Engineering, Sunchon National University, Jeonnam 57922, Republic of Korea
¹Biomedical Research Institute, Pusan National University Hospital, Pusan 49241, Republic of Korea
²Department of Biological and Environmental Engineering, Semyung University, Jecheon 27136, Republic of Korea
³Department of Biotechnology and Bio-Environmental Technology (BET) Research Institute, Chung-Ang University, Anseong, Gyeonggi-do, 456-756, Republic of Korea
⁴Department of Environmental Education, Mokpo National University, 1666 Youngsan Ro, Muan, Cheonggye Myeon 58554, Republic of Korea

E-mail:,

The pH-sensitive LMWSC-PCL di-block copolymer (LMP) was synthesized by radical polymerization between LMWSC and PCL macromere using potassium persulfate (KPS), and paclitaxel (PTX)- encapsulated LMP (LMPPTX) nanoparticles were prepared by sonication and dialysis method. To investigate pH-sensitive effect of LMP, its particle size was measured in neutral-pH and acidic-pH condition. In addition, PTX from LMPPTX was released greater under acidic-pH. Additionally, the cytotoxicity of LMP and LMPPTX was evaluated by MTT assay and the cellular uptake was analyzed by fluorescence microscopy and flow cytometry. Overall, the results suggest that pH-sensitive LMPPTX nanoparticles are an excellent anticancer agent to inhibit tumor growth.

Keywords:LMWSC;pH-sensitive diblock copolymer;Paclitaxel-encapsulated nanoparticle;Anticancer effect

[References]

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[Referenced By]

[1] Kim D, Lee ES, Oh KT, Gao ZG, Bae YH, Small, 4, 2043 (2008)

[2] Ye F, Guo H, Zhang H, He X, Acta Biomater., 6, 2212 (2010)

[3] Kore G, Kolate A, Nej A, Misra A, J. Nanosci. Nanotechnol., 14, 288 (2014)

[4] Lapteva M, Mondon K, Moller M, Gurny R, Kalia YN, Mol. Pharm., 11, 2989 (2014)

[5] Li Y, Bastakoti BP, Malgras V, Li C, Tang J, Kim JH, Yamauchi Y, Angew. Chem., 54, 11073 (2015)

[6] Xia H, Zhao Y, Tong R, Adv. Exp. Med. Biol., 880, 365 (2016)

[7] Patel MP, Patel RR, Patel JK, J. Pharm. Pharm. Sci., 13, 536 (2010)

[8] Cohen EM, Ding H, Kessinger CW, Khemtong C, Gao J, Sumer BD, Otolaryngol. Head Neck Surg., 143, 109 (2010)

[9] Yuan H, Lu LJ, Du YZ, Hu FQ, Mol. Pharm., 8, 225 (2011)

[10] Bhattarai N, Ramay HR, Chou SH, Zhang M, Int. J. Nanomedicine, 1, 181 (2006)

[11] Xu XY, Zhou JP, Li L, Zhang Y, Huo MR, Wang X, Lu L, Acta Pharm. Sin., 43, 743 (2008)

[12] Gu C, Le V, Lang M, Liu J, Colloids Surf. B: Biointerfaces, 116, 745 (2014)

[13] Alamdarnejad G, Sharif A, Taranejoo S, Janmaleki M, Kalaee MR, Dadgar M, Khakpour M, J. Mater. Sci. -Mater. Med., 24, 1939 (2013)

[14] Bernkop-Schnurch A, Dunnhaupt S, Eur. J. Pharm. Biopharm., 81, 463 (2012)

[15] Majedi FS, Hasani-Sadrabadi MM, Emami SH, Shokrgozar MA, VanDersarl JJ, Dashtimoghadam E, Bertsch A, Renaud P, Lab Chip, 13, 204 (2013)

[16] Termsarasab U, Cho HJ, Kim DH, Chong S, Chung SJ, Shim CK, Moon HT, Kim DD, Int. J. Pharm., 441, 373 (2013)

[17] Feng C, Wang Z, Jiang C, Kong M, Zhou X, Li Y, Cheng X, Chen X, Int. J. Pharm., 457, 158 (2013)

[18] Tajmir-Riahi HA, Nafisi S, Sanyakamdhorn S, Agudelo D, Chanphai P, Methods Mol. Biol., 1141, 165 (2014)

[19] Li N, Zhuang C, Wang M, Sun X, Nie S, Pan W, Int. J. Pharm., 379, 131 (2009)

[20] Amoozgar Z, Park J, Lin Q, Yeo Y, Mol. Pharm., 9, 1262 (2012)

[21] Jeong GW, Nah JW, Carbohydr. Polym., 178, 322 (2017)

[22] Chae SY, Son S, Lee M, Jang MK, Nah JW, J. Control. Release, 109, 330 (2005)

[23] Chae SY, Jang MK, Nah JW, J. Control. Release, 102, 383 (2005)

[24] Kim DG, Jeong YI, Choi C, Roh SH, Kang SK, Jang MK, Nah JW, Int. J. Pharm., 319, 130 (2006)

[25] Jeong YI, Kim DG, Jang MK, Nah JW, Carbohydr. Res., 343, 282 (2008)

[26] Jeong GW, Park JK, Nah JW, Appl. Chem. Eng., 29(2), 147 (2018)

[27] Jang MK, Jeong YI, Nah JW, Colloids Surf. B: Biointerfaces, 81, 530 (2010)

[28] Nam JP, Park SC, Kim TH, Jang JY, Choi C, Jang MK, Nah JW, Int. J. Pharm., 457, 124 (2013)

[29] Gu C, Le V, Lang M, Liu J, Colloids Surf. B: Biointerfaces, 116, 745 (2014)

[30] Huo M, Zou A, Yao C, Zhang Y, Zhou J, Wang J, Zhu Q, Li J, Zhang Q, Biomaterials, 33, 6393 (2012)

[31] Xie YT, Du YZ, Yuan H, Hu FQ, Int. J. Nanomed., 7, 3235 (2012)

[32] Kim DG, Choi C, Jeong YI, Jang MK, Nah JW, Kang SK, Bang MS, Macromol. Res., 14(1), 66 (2006)

[33] Seo DH, Jeong YI, Kim DG, Jang MJ, Jang MK, Nah JW, Colloids Surf. B: Biointerfaces, 69, 157 (2009)

[34] Ganji F, Abdekhodaie MJ, Carbohydr. Polym., 74, 435 (2008)

[35] Hsu SC, Don TM, Chiu WY, Polym. Degrad. Stab., 75, 73 (2002)

[36] Kusrini E, Shiong NS, Harahap Y, Yulizar Y, Dianursanti D, Arbianti R, Pudjiastuti AR, IJTech, 6, 11 (2015)

[37] Kweon H, Yoo MK, Park IK, Kim TH, Lee HC, Lee HS, Oh JS, Akaike T, Cho CS, Biomaterials, 24, 801 (2003)

[38] Liu G, Li K, Wang H, J. Biomater. Appl., 31, 1039 (2017)

[39] Thotakura N, Dadarwal M, Kumar R, Singh B, Sharma G, Kumar P, Katare OP, Raza K, Int. J. Biol. Macromol., 102, 1220 (2017)

[40] Al-Ghananeem AM, Saeed H, Florence R, Yokel RA, Malkawi AH, J. Drug Target., 18, 381 (2010)

[41] Babu A, Ramesh R, Marine Drugs, 15 (2017)

[42] Hu FQ, Meng P, Dai YQ, Du YZ, You J, Wei XH, Yuan H, Eur. J. Pharm. Biopharm., 70, 749 (2008)

[43] Chung TW, Liu DZ, Hsieh JH, Fan XC, Yang JD, Chen JH, J. Nanosci. Nanotechnol., 6, 2902 (2006)

[44] Mazzarino L, Otsuka I, Halila S, Ldos SB, Mazzucco S, Santos-Silva MC, Lemos-Senna E, Borsali R, Macromol. Biosci., 14, 709 (2014)

[45] Tannock IF, Rotin D, Cancer Res., 49, 4373 (1989)