Citation: Dan-Hua Zhou, Guan Zhang, Qing-Song Yu, Zhi-Hua Gan. Folic Acid Modified Polymeric Micelles for Intravesical Instilled Chemotherapy[J]. Chinese Journal of Polymer Science, ;2018, 36(4): 479-487. doi: 10.1007/s10118-018-2009-y shu

Folic Acid Modified Polymeric Micelles for Intravesical Instilled Chemotherapy

a.
National University of Singapore Environmental Research Institute(NERI), National University of Singapore, Singapore 117576, Singapore
b.
Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Organic-inorganic Composite Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
c.
Department of Urology, China-Japan Friendship Hospital, Beijing 100029, China

Corresponding author: Qing-Song Yu, yuqs@mail.buct.edu.cn Zhi-Hua Gan, zhgan@mail.buct.edu.cn
Received Date: 28 June 2017
Accepted Date: 12 July 2017
Available Online: 20 December 2018

In this study, a targeting micellar drug delivery system was developed for intravesical instilled chemotherapy of bladder cancer. The amphiphilic diblock copolymer poly(ε-caprolactone)-block-poly(ethylene glycol) (PCL-b-PEO) with functional amino group (NH₂) at the end of PEO block was synthesized. Then the copolymer was conjugated with folic acid (FA) and fluorescein isothiocyannate (FITC) via the PEO-NH₂ terminus, and then assembled into micelles with the target moiety and fluorescence labeling. In addition, drug loaded micelles were also fabricated with anticancer drug doxorubicin (DOX) encapsulated in the hydrophobic core. The micelles were characterized in terms of size, drug loaded efficiency and critical micellization concentration (CMC) by means of DLS, UV and fluorescence spectra. In vitro cellular uptake and cytotoxicity studies showed that FA modified PCL-b-PEO-FA micelles have a greater targeting efficiency to human bladder cancer cell (T-24 cell) compared to PCL-b-PEO-NH₂ micelles due to the conjugation of FA on the surface, while no targeting effect to normal tissue originated human embryonic kidney 293 (HEK-293) cells was observed, enabling the micelles a promising drug carrier for intravesical instilled chemotherapy of bladder cancer.
- Targeted drug delivery,
- Superficial bladder cancer,
- Intravesical instilled chemotherapy,
- Folic acid,
- Micelles
1. [1]
  Sun P., Zhou D., Gan Z.. Novel reduction-sensitive micelles for triggered intracellular drug release[J]. J. Control. Release, 2011,155(1):96-103. doi: 10.1016/j.jconrel.2010.11.005
2. [2]
  Nie S., Xing Y., Kim G. J., Simons J. W.. Nanotechnology applications in cancer[J]. Annu. Rev. Biomed. Eng., 2007,9(1):257-288. doi: 10.1146/annurev.bioeng.9.060906.152025
3. [3]
  GuhaSarkar S., Banerjee R.. Intravesical drug delivery:challenges, current status, opportunities and novel strategies[J]. J. Control. Release, 2010,148(2):147-159. doi: 10.1016/j.jconrel.2010.08.031
4. [4]
  Shelley M. D., Mason M. D., Kynaston H.. Intravesical therapy for superficial bladder cancer:a systematic review of randomised trials and meta-analyses[J]. Cancer Treat. Rev., 2010,36(3):195-205. doi: 10.1016/j.ctrv.2009.12.005
5. [5]
  Parkin D. M.. The global burden of urinary bladder cancer[J]. Scand. J. Urology Nephr., 2008,42:12-20.
6. [6]
  Ploeg M., Aben K. K. H., Kiemeney L. A.. The present and future burden of urinary bladder cancer in the world[J]. World J. Urology, 2009,27(3):289-293. doi: 10.1007/s00345-009-0383-3
7. [7]
  Beardo V. P., Gamaza M. R., Gavira M. R.. Toxicity of intravesical gemcitabine in superficial bladder cancer treatment[J]. Farm Hosp, 2014,38(3):249-251.
8. [8]
  Rajala P., Liukkonen T., Raitanen M., Rintala E., Kaasinen E., Helle M., Lukkarinen O., Finnbladder G.. Transurethral resection with perioperative instillation of interferon-alpha or epirubicin for the prophylaxis of recurrent primary superficial bladder cancer:A prospective randomized multicenter study-finnbladder iii[J]. J. Urology, 1999,161(4):1133-1135. doi: 10.1016/S0022-5347(01)61609-4
9. [9]
  Bellmunt J., Guix M.. New agents for bladder cancer[J]. Ann. Oncol., 2010,21:56-58.
10. [10]
  Li X., Qian Y., Liu T., Hu X., Zhang G., You Y., Liu S.. Amphiphilic multiarm star block copolymer-based multifunctional unimolecular micelles for cancer targeted drug delivery and mr imaging[J]. Biomaterials, 2011,32(27):6595-6605. doi: 10.1016/j.biomaterials.2011.05.049
11. [11]
  Jagur-Grodzinski J.. Polymers for targeted and/or sustained drug delivery, Polym[J]. Adv. Technol.,, 2009,20(7):595-606. doi: 10.1002/pat.v20:7
12. [12]
  Cho H. K., Cheong I. W., Lee J. M., Kim J. H.. Polymeric nanoparticles, micelles and polymersomes from amphiphilic block copolymer[J]. Korean J. Chem. Eng., 2010,27(3):731-740. doi: 10.1007/s11814-010-0216-5
13. [13]
  Li X. R., Li P. Z., Zhang Y. H., Zhou Y. X., Chen X. W., Huang Y. Q., Liu Y.. Novel mixed polymeric micelles for enhancing delivery of anticancer drug and overcoming multidrug resistance in tumor cell lines simultaneously[J]. Pharm. Res., 2010,27(8):1498-1511. doi: 10.1007/s11095-010-0147-1
14. [14]
  Bilensoy E., Sarisozen C., Esendagl I.G., Dogan A. L., Aktas Y., Sen M., Mungan N.A.. Intravesical cationic nanoparticles of chitosan and polycaprolactone for the delivery of mitomycin C to bladder tumors, Int[J]. J. Pharm.,, 2009,371(1-2):170-176.
15. [15]
  Kim S. W., Lee S. J., Cho Y. H., Yoon M. S., Lee C.H.. The anticancer efficacy and toxicity of oral paclitaxel-loaded lipid nanoparticle in a C3H2 bladder cancer mice[J]. Eur. Urology Suppl., 2005,4(3):84-84.
16. [16]
  Zhou D., Zhang G., Gan Z.. c(RGDfk) decorated micellar drug delivery system for intravesical instilled chemotherapy of superficial bladder cancer[J]. J. Control. Release, 2013,169(3):204-210. doi: 10.1016/j.jconrel.2013.01.025
17. [17]
  Lu Y. J., Low P. S.. Folate-mediated delivery of macromolecular anticancer therapeutic agents[J]. Adv. Drug Deliv. Rev., 2002,54(5):675-693. doi: 10.1016/S0169-409X(02)00042-X
18. [18]
  Ross J. F., Chaudhuri P. K., Ratnam M.. Differential regulation of folate receptor isoforms in normal and malignant-tissues in vivo and in established cell-lines-physiological and clinical implications[J]. Cancer, 1994,73(9):2432-2443. doi: 10.1002/(ISSN)1097-0142
19. [19]
  Guo X., Shi C., Wang J., Di S., Zhou S.. pH-triggered intracellular release from actively targeting polymer micelles[J]. Biomaterials, 2013,34(18):4544-4554. doi: 10.1016/j.biomaterials.2013.02.071
20. [20]
  Yoo H. S., Park T. G.. Folate receptor targeted biodegradable polymeric doxorubicin micelles[J]. J. Control. Release, 2004,96(2):273-283. doi: 10.1016/j.jconrel.2004.02.003
21. [21]
  Shi C., Guo X., Qu Q., Tang Z., Wang Y., Zhou S.. Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles[J]. Biomaterials, 2014,35(30):8711-8722. doi: 10.1016/j.biomaterials.2014.06.036
22. [22]
  Zhang Y., Sun P. J., Gan Z. H.. Biodegradable amphiphilic block copolymers containing functionalized peo blocks:Controlled synthesis and biomedical potentials[J]. Sci. Chi. Chem., 2010,53(3):519-527. doi: 10.1007/s11426-010-0095-y
23. [23]
  Fernandes R. M. F., Marques E. F., Silva B. F. B., Wang Y. J.. Micellization behavior of a catanionic surfactant with high solubility mismatch composition, temperature, and salt effects, J[J]. Mol. Liq.,, 2010,157(2-3):113-118. doi: 10.1016/j.molliq.2010.08.014
24. [24]
  Wei X., Gong C., Gou M., Fu S., Guo Q., Shi S., Luo F., Guo G., Qiu L., Qian Z.. Biodegradable poly(ε-caprolactone)-poly(ethylene glycol) copolymers as drug delivery system[J]. Int. J. Pharm., 2009,381(1):1-18. doi: 10.1016/j.ijpharm.2009.07.033
25. [25]
  Yu G. Q., Zhang Y., Shi X. D., Li Z. S., Gan Z. H.. Surface property and in vitro biodegradation of microspheres fabricated by poly(ε-caprolactone-b-ethylene oxide) diblock copolymers[J]. J. Biomed. Mater. Res. Part A, 2008,84A(4):926-939. doi: 10.1002/(ISSN)1552-4965
26. [26]
  Lu T. C., Sun J., Chen X. X., Zhang P. B., Jing X. B.. Folate-conjugated micelles and their folate-receptor-mediated endocytosis[J]. Macromol. Biosci., 2009,9(11):1059-1068. doi: 10.1002/mabi.v9:11
27. [27]
  Cho H. K., Lone S., Kim D. D., Choi J. H., Choi S. W., Cho J. H., Kim J. H., Cheong I. W.. Synthesis and characterization of fluorescein isothiocyanate (FITC)-labeled PEO-PCL-PEO triblock copolymers for topical delivery[J]. Polymer, 2009,50(11):2357-2364. doi: 10.1016/j.polymer.2009.03.032
28. [28]
  Liu Y. T., Li K., Pan J., Liu B., Feng S. S.. Folic acid conjugated nanoparticles of mixed lipid monolayer shell and biodegradable polymer core for targeted delivery of docetaxel[J]. Biomaterials, 2010,31(2):330-338. doi: 10.1016/j.biomaterials.2009.09.036
29. [29]
  Prabaharan M., Grailer J. J., Pilla S., Steeber D. A., Gong S.. Amphiphilic multi-arm-block copolymer conjugated with doxorubicin via pH-sensitive hydrazone bond for tumor-targeted drug delivery[J]. Biomaterials, 2009,30(29):5757-5766. doi: 10.1016/j.biomaterials.2009.07.020
30. [30]
  Seow W. Y., Xue J. M., Yang Y. Y.. Targeted and intracellular delivery of Paclitaxel using multi-functional polymeric micelles[J]. Biomaterials, 2007,28(9):1730-40. doi: 10.1016/j.biomaterials.2006.11.039
1. [1]
  Yihan Zhou , Duo Gao , Yaying Wang , Li Liang , Qingyu Zhang , Wenwen Han , Jie Wang , Chunliu Zhu , Xinxin Zhang , Yong Gan . Worm-like micelles facilitate the intestinal mucus diffusion and drug accumulation for enhancing colorectal cancer therapy. Chinese Chemical Letters, 2024, 35(6): 108967-. doi: 10.1016/j.cclet.2023.108967
2. [2]
  Xiangqian Cao , Chenkai Yang , Xiaodong Zhu , Mengxin Zhao , Yilin Yan , Zhengnan Huang , Jinming Cai , Jingming Zhuang , Shengzhou Li , Wei Li , Bing Shen . Synergistic enhancement of chemotherapy for bladder cancer by photothermal dual-sensitive nanosystem with gold nanoparticles and PNIPAM. Chinese Chemical Letters, 2024, 35(8): 109199-. doi: 10.1016/j.cclet.2023.109199
3. [3]
  Mengjuan Sun , Muye Zhou , Yifang Xiao , Hailei Tang , Jinhua Chen , Ruitao Zhang , Chunjiayu Li , Qi Ya , Qian Chen , Jiasheng Tu , Qiyue Wang , Chunmeng Sun . Reversibly size-switchable polyion complex micelles for antiangiogenic cancer therapy. Chinese Chemical Letters, 2024, 35(7): 109110-. doi: 10.1016/j.cclet.2023.109110
4. [4]
  Qiuyu Ming , Huijun Jiang , Zhihao Zhang . A Sightseeing Tour of Folic Acid Processing Plant. University Chemistry, 2024, 39(9): 11-15. doi: 10.12461/PKU.DXHX202404092
5. [5]
  Linghui Zou , Meng Cheng , Kaili Hu , Jianfang Feng , Liangxing Tu . Vesicular drug delivery systems for oral absorption enhancement. Chinese Chemical Letters, 2024, 35(7): 109129-. doi: 10.1016/j.cclet.2023.109129
6. [6]
  Fengjie Liu , Fansu Meng , Zhenjiang Yang , Huan Wang , Yuehong Ren , Yu Cai , Xingwang Zhang . Exosome-biomimetic nanocarriers for oral drug delivery. Chinese Chemical Letters, 2024, 35(9): 109335-. doi: 10.1016/j.cclet.2023.109335
7. [7]
  Tong Zhang , Chao Sun , Shubin Yang , Zimin Cai , Sifeng Zhu , Wendian Liu , Yun Luan , Cheng Wang . Inhalation of taraxasterol loaded mixed micelles for the treatment of idiopathic pulmonary fibrosis. Chinese Chemical Letters, 2024, 35(8): 109248-. doi: 10.1016/j.cclet.2023.109248
8. [8]
  Weijian Zhang , Xianyu Deng , Liying Wang , Jian Wang , Xiuting Guo , Lianggui Huang , Xinyi Wang , Jun Wu , Linjia Jiang . Poly(ferulic acid) nanocarrier enhances chemotherapy sensitivity of acute myeloid leukemia by selectively targeting inflammatory macrophages. Chinese Chemical Letters, 2024, 35(9): 109422-. doi: 10.1016/j.cclet.2023.109422
9. [9]
  Lin Li , Bingjun Sun , Jin Sun , Lin Chen , Zhonggui He . Binary prodrug nanoassemblies combining chemotherapy and ferroptosis activation for efficient triple-negative breast cancer therapy. Chinese Chemical Letters, 2024, 35(10): 109538-. doi: 10.1016/j.cclet.2024.109538
10. [10]
  Yiqiao Chen , Ao Liu , Biwen Yang , Zhenzhen Li , Binggang Ye , Zhouyi Guo , Zhiming Liu , Haolin Chen . Photoluminescence and photothermal conversion in boric acid derived carbon dots for targeted microbial theranostics. Chinese Chemical Letters, 2024, 35(9): 109295-. doi: 10.1016/j.cclet.2023.109295
11. [11]
  Ningyue Xu , Jun Wang , Lei Liu , Changyang Gong . Injectable hydrogel-based drug delivery systems for enhancing the efficacy of radiation therapy: A review of recent advances. Chinese Chemical Letters, 2024, 35(8): 109225-. doi: 10.1016/j.cclet.2023.109225
12. [12]
  Dexuan Xiao , Tianyu Chen , Tianxu Zhang , Sirong Shi , Mei Zhang , Xin Qin , Yunkun Liu , Longjiang Li , Yunfeng Lin . Transdermal treatment for malignant melanoma by aptamer-modified tetrahedral framework nucleic acid delivery of vemurafenib. Chinese Chemical Letters, 2024, 35(4): 108602-. doi: 10.1016/j.cclet.2023.108602
13. [13]
  Yu Qin , Mingyang Huang , Chenlu Huang , Hannah L. Perry , Linhua Zhang , Dunwan Zhu . O₂-generating multifunctional polymeric micelles for highly efficient and selective photodynamic-photothermal therapy in melanoma. Chinese Chemical Letters, 2024, 35(7): 109171-. doi: 10.1016/j.cclet.2023.109171
14. [14]
  Yi Cao , Xiaojiao Ge , Yuanyuan Wei , Lulu He , Aiguo Wu , Juan Li . Tumor microenvironment-activatable neuropeptide-drug conjugates enhanced tumor penetration and inhibition via multiple delivery pathways and calcium deposition. Chinese Chemical Letters, 2024, 35(4): 108672-. doi: 10.1016/j.cclet.2023.108672
15. [15]
  Qiang Li , Jiangbo Fan , Hongkai Mu , Lin Chen , Yongzhen Yang , Shiping Yu . Nucleus-targeting orange-emissive carbon dots delivery adriamycin for enhanced anti-liver cancer therapy. Chinese Chemical Letters, 2024, 35(6): 108947-. doi: 10.1016/j.cclet.2023.108947
16. [16]
  Wenjia Wang , Xingyue He , Xiaojie Wang , Tiantian Zhao , Osamu Muraoka , Genzoh Tanabe , Weijia Xie , Tianjiao Zhou , Lei Xing , Qingri Jin , Hulin Jiang . Glutathione-depleted cyclodextrin pseudo-polyrotaxane nanoparticles for anti-inflammatory oxaliplatin (Ⅳ) prodrug delivery and enhanced colorectal cancer therapy. Chinese Chemical Letters, 2024, 35(4): 108656-. doi: 10.1016/j.cclet.2023.108656
17. [17]
  Wenyi Mei , Lijuan Xie , Xiaodong Zhang , Cunjian Shi , Fengzhi Wang , Qiqi Fu , Zhenjiang Zhao , Honglin Li , Yufang Xu , Zhuo Chen . Design, synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells. Chinese Chemical Letters, 2024, 35(5): 108825-. doi: 10.1016/j.cclet.2023.108825
18. [18]
  Huipeng Zhao , Xiaoqiang Du . Polyoxometalates as the redox anolyte for efficient conversion of biomass to formic acid. Chinese Journal of Structural Chemistry, 2024, 43(2): 100246-100246. doi: 10.1016/j.cjsc.2024.100246
19. [19]
  Dan-Ying Xing , Xiao-Dan Zhao , Chuan-Shu He , Bo Lai . Kinetic study and DFT calculation on the tetracycline abatement by peracetic acid. Chinese Chemical Letters, 2024, 35(9): 109436-. doi: 10.1016/j.cclet.2023.109436
20. [20]
  Jinyu Guo , Yandai Lin , Shaohua He , Yueqing Chen , Fenglu Li , Renjie Ruan , Gaoxing Pan , Hexin Nan , Jibin Song , Jin Zhang . Utilizing dual-responsive iridium(Ⅲ) complex for hepatocellular carcinoma: Integrating photoacoustic imaging with chemotherapy and photodynamic therapy. Chinese Chemical Letters, 2024, 35(9): 109537-. doi: 10.1016/j.cclet.2024.109537

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(653)
HTML views(34)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142