Citation: Dai Jun-Tao, Zhang Yu, Li Heng-Chao, Deng Yong-Hui, Elzatahry Ahmed A., Alghamdi Abdulaziz, Fu De-Liang, Jiang Yong-Jian, Zhao Dong-Yuan. Enhancement of gemcitabine against pancreatic cancer by loading in mesoporous silica vesicles[J]. Chinese Chemical Letters, ;2017, 28(3): 531-536. doi: 10.1016/j.cclet.2016.11.008 shu

Enhancement of gemcitabine against pancreatic cancer by loading in mesoporous silica vesicles

a.
Department of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
b.
Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), Fudan University, Shanghai 200433, China
c.
State Key Lab of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China
d.
Materials Science and Technology Program, College of Arts and Sciences, Qatar Department of Chemistry, Qatar University, PO Box 2713, Doha, Qatar
e.
College of Science, King Saud University, Riyadh 11451, Saudi Arabia

Corresponding author: Fu De-Liang, surgeonfu@163.com Jiang Yong-Jian, yongjianjiang@fudan.edu.cn

Received Date: 30 August 2016
Revised Date: 17 October 2016
Accepted Date: 27 October 2016
Available Online: 11 March 2016

Figures(6)

Gemcitabine (Gem) is currently the first-line chemotherapeutic drug in management of pancreatic cancer, however the therapeutic efficacy of Gem is limited due to its short half-life and poor cell membrane permeability. Here we designed mesoporous silica vesicles (MSVs) with large pore sizes as a novel drug delivery system. The MSVs were synthesized using cetyltrimethyl ammonium bromide (CTAB) as a structure-directing agent, tetraethoxysilane (TEOS) as silica source in n-hexane/water biliquid system. By virtue of the large pore size and large pore volume of the MSVs, Gem was loaded into the mesoporous of MSVs via "nanocasting" method. In vitro drug release experiments of gemcitabineloaded MSVs showed an accelerating release of gemcitabine in acidic condition. These fluorescently labeled MSVs could be effectively internalized by both a human (BxPC-3) and a mouse pancreatic cancer cell lines (Pan02). Additionally, some MSVs could even reach the nuclei of the pancreatic cancer cells. Cell viability assays demonstrated that gemcitabine-loaded MSVs exhibited enhanced anticancer activity in inhibiting the proliferation of BxPC-3 and Pan02 cells compared with free Gem, while the MSVs alone showed no significant cytotoxicity. Our results indicate that our synthesized MSVs might represent a promising novel drug delivery platform for the treatment of pancreatic cancer.
- Gemcitabine,
- Mesoporous silica vesicles,
- Drug delivery,
- Pancreatic cancer,
- Drug release
1. [1]
  Chen W., Zheng R., Baade P.D.. Cancer statistics in China, 2015[J]. CA:Cancer J. Clin., 2016,66:115-132. doi: 10.3322/caac.21338
2. [2]
  Rahib L., Smith B.D., Aizenberg R.. Projecting cancer incidence and deaths to 2030:the unexpected burden of thyroid, liver, and pancreas cancers in the United States[J]. Cancer Res., 2014,74:2913-2921. doi: 10.1158/0008-5472.CAN-14-0155
3. [3]
  Peixoto R.D., Ho M., Renouf D.J.. Eligibility of metastatic pancreatic cancer patients for first-line palliative intent nab-paclitaxel plus gemcitabine versus FOLFIRINOX[J]. Am. J. Clin. Oncol., 2015. doi: 10.1097/coc.0000000000000193
4. [4]
  Heinemann V., Reni M., Ychou M.. Tumour-stroma interactions in pancreatic ductal adenocarcinoma:rationale and current evidence for new therapeutic strategies[J]. Cancer Treat. Rev., 2014,40:118-128. doi: 10.1016/j.ctrv.2013.04.004
5. [5]
  Reid J.M., Qu W., Safgren S.L.. Phase Ⅰ trial and pharmacokinetics of gemcitabine in children with advanced solid tumors[J]. J. Clin. Oncol., 2004,22:2445-2451. doi: 10.1200/JCO.2004.10.142
6. [6]
  Moog R., Burger A.M., Brandl M.. Change in pharmacokinetic and pharmacodynamic behavior of gemcitabine in human tumor xenografts upon entrapment in vesicular phospholipid gels[J]. Cancer Chemother. Pharmacol., 2002,49:356-366. doi: 10.1007/s00280-002-0428-4
7. [7]
  Farrell J.J., Elsaleh H., Garcia M.. Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer[J]. Gastroenterology, 2009,136:187-195. doi: 10.1053/j.gastro.2008.09.067
8. [8]
  DallaPozza E., Lerda C., Costanzo C.. Targeting gemcitabine containing liposomes to CD44 expressing pancreatic adenocarcinoma cells causes an increase in the antitumoral activity[J]. Biochim. Biophys. Acta, 2013,1828:1396-1404. doi: 10.1016/j.bbamem.2013.01.020
9. [9]
  Zhu S.J., Wonganan P., Lansakara P.D.. The effect of the acid-sensitivity of 4-(N)-stearoyl gemcitabine-loaded micelles on drug resistance caused by RRM1 overexpression[J]. Biomaterials, 2013,34:2327-2339. doi: 10.1016/j.biomaterials.2012.11.053
10. [10]
  Arias J.L., Reddy L.H., Couvreur P.. Polymeric nanoparticulate system augmented the anticancer therapeutic efficacy of gemcitabine[J]. J. Drug Target., 2009,17:586-598. doi: 10.1080/10611860903105739
11. [11]
  Malfanti A., Miletto I., Bottinelli E.. Delivery of gemcitabine prodrugs employing mesoporous silica nanoparticles[J]. Molecules, 2016,21522. doi: 10.3390/molecules21040522
12. [12]
  Meng H., Wang M.Y., Liu H.Y.. Use of a lipid-coated mesoporous silica nanoparticle platform for synergistic gemcitabine and paclitaxel delivery to human pancreatic cancer in mice[J]. ACS Nano, 2015,9:3540-3557. doi: 10.1021/acsnano.5b00510
13. [13]
  Shao J.X., Xuan M.J., Si T.Y., Dai L.R., He Q.. Biointerfacing polymeric microcapsules for in vivo near-infrared light-triggered drug release[J]. Nanoscale, 2015,7:19092-19098. doi: 10.1039/C5NR06350G
14. [14]
  Shao J.X., Xuan M.J., Dai L.R.. Near-infrared-activated nanocalorifiers in microcapsules:vapor bubble generation for in vivo enhanced cancer therapy[J]. Angew. Chem. Int. Ed. Engl., 2015,54:12782-12787. doi: 10.1002/anie.201506115
15. [15]
  Xuan M.J., Shao J.X., Dai L.R., He Q., Li J.B.. Macrophage cell membrane camouflaged mesoporous silica nanocapsulesfor in vivo cancer therapy[J]. Adv. Healthc. Mater., 2015,4:1645-1652. doi: 10.1002/adhm.v4.11
16. [16]
  Xuan M.J., Shao J.X., Dai L.R., Li J.B., He Q.. Macrophage cell membrane camouflaged au nanoshells for in vivo prolonged circulation life and enhanced cancer photothermal therapy[J]. ACS Appl. Mater. Interfaces, 2016,8:9610-9618. doi: 10.1021/acsami.6b00853
17. [17]
  Mora-Huertas C.E., Fessi H., Elaissari A.. Polymer-based nanocapsules for drug delivery[J]. Int. J. Pharm., 2010,385:113-142. doi: 10.1016/j.ijpharm.2009.10.018
18. [18]
  Paolino D., Cosco D., Celano M.. Gemcitabine-loaded biocompatible nanocapsules for the effective treatment of human cancer[J]. Nanomedicine (Lond.), 2013,8:193-201. doi: 10.2217/nnm.12.101
19. [19]
  Field C.B., Behrenfeld M.J., Randerson J.T., Falkowski P.. Primary production of the biosphere:integrating terrestrial and oceanic components[J]. Science, 1998,281:237-240. doi: 10.1126/science.281.5374.237
20. [20]
  Meng F.H., Zhong Z.Y., Feijen J.. Stimuli-responsive polymersomes for programmed drug delivery[J]. Biomacromolecules, 2009,10:197-209. doi: 10.1021/bm801127d
21. [21]
  Tang F.Q., Li L.L., Chen D.. Mesoporous silica nanoparticles:synthesis, biocompatibility and drug delivery[J]. Adv. Mater., 2012,24:1504-1534. doi: 10.1002/adma.201104763
22. [22]
  Sood A., Panchagnula R.. Peroral route:an opportunity for protein and peptide drug delivery[J]. Chem. Rev., 2001,101:3275-3303. doi: 10.1021/cr000700m
23. [23]
  Zhang J., Karmakar S., Yu M.H.. Synthesis of silica vesicles with controlled entrance size for high loading, sustained release, and cellular delivery of therapeutical proteins[J]. Small, 2014,10:5068-5076.
24. [24]
  Immordino M.L., Brusa P., Rocco F.. Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing lipophilic gemcitabine prodrugs[J]. J. Control. Release, 2004,100:331-346. doi: 10.1016/j.jconrel.2004.09.001
25. [25]
  Paolino D., Cosco D., Racanicchi L.. Gemcitabine-loaded PEGylatedunilamellar liposomes vs GEMZAR:biodistribution, pharmacokinetic features and in vivo antitumoractivity[J]. J. Control. Release, 2010,144:144-150. doi: 10.1016/j.jconrel.2010.02.021
26. [26]
  Tao X.M., Wang J.C., Wang J.B.. Enhanced anticancer activity of gemcitabine coupling with conjugated linoleic acid against human breast cancer in vitro and in vivo[J]. Eur. J. Pharm. Biopharm., 2012,82:401-409. doi: 10.1016/j.ejpb.2012.06.007
27. [27]
  Garcion E., Lamprecht A., Heurtault B.. A new generation of anticancer drug-loaded, colloidal vectors reverses multidrug resistance in glioma and reduces tumor progression in rats[J]. Mol. Cancer Ther., 2006,5:1710-1722. doi: 10.1158/1535-7163.MCT-06-0289
28. [28]
  Nahire R., Haldar M.K., Paul S.. Multifunctional polymersomes for cytosolic delivery of gemcitabine and doxorubicin to cancer cells[J]. Biomaterials, 2014,35:6482-6497. doi: 10.1016/j.biomaterials.2014.04.026
29. [29]
  Ulbrich K., Subr V.. Polymeric anticancer drugs with pH-controlled activation[J]. Adv. Drug Deliv. Rev., 2004,56:1023-1050. doi: 10.1016/j.addr.2003.10.040
30. [30]
  Panyam J., Zhou W.Z., Prabha S., Sahoo S.K., Labhasetwar V.. Rapid endolysosomal escape of poly (_DL-lactide-co-glycolide) nanoparticles:implications for drug and gene delivery[J]. FASEB J., 2002,16:1217-1226. doi: 10.1096/fj.02-0088com
31. [31]
  Rejman J., Oberle V., Zuhorn I.S., Hoekstra D.. Size-dependent internalizationof particles via the pathways of clathrin-and caveolae-mediated endocytosis[J]. Biochem. J., 2004,377:159-169. doi: 10.1042/bj20031253
32. [32]
  Tanaka M., Okazaki T., Suzuki H., Abbruzzese J.L., Li D.H.. Association of multidrug resistance gene polymorphisms with pancreatic cancer outcome[J]. Cancer, 2011,117:744-751. doi: 10.1002/cncr.v117.4
33. [33]
  Zhang Y., Yue Q., Jiang Y.J.. A facile biliquid-interface co-assembly synthesis of mesoporous vesicles with large pore sizes[J]. CrystEngComm, 2016,18:4343-4348. doi: 10.1039/C5CE02592C
34. [34]
  Deng Y.H., Wang C.C., Shen X.Z.. Preparation, characterization, and application of multistimuli-responsive microspheres with fluorescencelabeled magnetic cores and thermoresponsive shells[J]. Chemistry, 2005,11:6006-6013. doi: 10.1002/(ISSN)1521-3765
1. [1]
  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
2. [2]
  Tong Tong , Lezong Chen , Siying Wu , Zhong Cao , Yuanbin Song , Jun Wu . Establishment of a leucine-based poly(ester amide)s library with self-anticancer effect as nano-drug carrier for colorectal cancer treatment. Chinese Chemical Letters, 2024, 35(12): 109689-. doi: 10.1016/j.cclet.2024.109689
3. [3]
  Zhilong Xie , Guohui Zhang , Ya Meng , Yefei Tong , Jian Deng , Honghui Li , Qingqing Ma , Shisong Han , Wenjun Ni . A natural nano-platform: Advances in drug delivery system with recombinant high-density lipoprotein. Chinese Chemical Letters, 2024, 35(11): 109584-. doi: 10.1016/j.cclet.2024.109584
4. [4]
  Xingqun Pu , Rongrong Liu , Yuting Xie , Chenjing Yang , Jingyi Chen , Baoling Guo , Chun-Xia Zhao , Peng Zhao , Jian Ruan , Fangfu Ye , David A Weitz , Dong Chen . One-step preparation of biocompatible amphiphilic dimer nanoparticles with tunable particle morphology and surface property for interface stabilization and drug delivery. Chinese Chemical Letters, 2025, 36(3): 109820-. doi: 10.1016/j.cclet.2024.109820
5. [5]
  Yuanzheng Wang , Chen Zhang , Shuyan Han , Xiaoli Kong , Changyun Quan , Jun Wu , Wei Zhang . Cancer cell membrane camouflaged biomimetic gelatin-based nanogel for tumor inhibition. Chinese Chemical Letters, 2024, 35(11): 109578-. doi: 10.1016/j.cclet.2024.109578
6. [6]
  Makhloufi Zoulikha , Zhongjian Chen , Jun Wu , Wei He . Approved delivery strategies for biopharmaceuticals. Chinese Chemical Letters, 2025, 36(2): 110225-. doi: 10.1016/j.cclet.2024.110225
7. [7]
  Jing Zhang , Charles Wang , Yaoyao Zhang , Haining Xia , Yujuan Wang , Kun Ma , Junfeng Wang . Application of magnetotactic bacteria as engineering microrobots: Higher delivery efficiency of antitumor medicine. Chinese Chemical Letters, 2024, 35(10): 109420-. doi: 10.1016/j.cclet.2023.109420
8. [8]
  Jiaqi Huang , Renjiang Kong , Yanmei Li , Ni Yan , Yeyang Wu , Ziwen Qiu , Zhenming Lu , Xiaona Rao , Shiying Li , Hong Cheng . Feedback enhanced tumor targeting delivery of albumin-based nanomedicine to amplify photodynamic therapy by regulating AMPK signaling and inhibiting GSTs. Chinese Chemical Letters, 2024, 35(8): 109254-. doi: 10.1016/j.cclet.2023.109254
9. [9]
  Lihang Wang , Mary Li Javier , Chunshan Luo , Tingsheng Lu , Shudan Yao , Bing Qiu , Yun Wang , Yunfeng Lin . Research advances of tetrahedral framework nucleic acid-based systems in biomedicine. Chinese Chemical Letters, 2024, 35(11): 109591-. doi: 10.1016/j.cclet.2024.109591
10. [10]
  Yong-Dan Zhao , Yidan Wang , Rongrong Wang , Lina Chen , Hengtong Zuo , Xi Wang , Jihong Qiang , Geng Wang , Qingxia Li , Canqi Ping , Shuqiu Zhang , Hao Wang . Reversing artemisinin resistance by leveraging thermo-responsive nanoplatform to downregulating GSH. Chinese Chemical Letters, 2024, 35(6): 108929-. doi: 10.1016/j.cclet.2023.108929
11. [11]
  Keyang Li , Yanan Wang , Yatao Xu , Guohua Shi , Sixian Wei , Xue Zhang , Baomei Zhang , Qiang Jia , Huanhua Xu , Liangmin Yu , Jun Wu , Zhiyu He . Flash nanocomplexation (FNC): A new microvolume mixing method for nanomedicine formulation. Chinese Chemical Letters, 2024, 35(10): 109511-. doi: 10.1016/j.cclet.2024.109511
12. [12]
  Yinglan Yu , Sajid Hussain , Jianping Qi , Lei Luo , Xuemei Zhang . Mechanisms and applications: Cargos transport to basolateral membranes in polarized epithelial cells. Chinese Chemical Letters, 2024, 35(12): 109673-. doi: 10.1016/j.cclet.2024.109673
13. [13]
  Han Wu , Yumei Wang , Zekai Ren , Hailin Cong , Youqing Shen , Bing Yu . The nanocarrier strategy for crossing the blood-brain barrier in glioma therapy. Chinese Chemical Letters, 2025, 36(4): 109996-. doi: 10.1016/j.cclet.2024.109996
14. [14]
  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
15. [15]
  Yujie Li , Ya-Nan Wang , Yin-Gen Luo , Hongcai Yang , Jinrui Ren , Xiao Li . Advances in synthetic biology-based drug delivery systems for disease treatment. Chinese Chemical Letters, 2024, 35(11): 109576-. doi: 10.1016/j.cclet.2024.109576
16. [16]
  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
17. [17]
  Jiaxu Wang , Jinxie Zhang , Xiuping Wang , Jingying Wang , Lina Chen , Jiahui Cao , Wei Cao , Siyu Liang , Ping Luan , Ke Zheng , Xiao-Kun Ouyang , Li Gao , Xiaowen Ou , Fan Zhang , Meitong Ou , Lin Mei . CaCO₃-coated hollow mesoporous silica nanoparticles for pH-responsive fungicides release. Chinese Chemical Letters, 2024, 35(12): 109697-. doi: 10.1016/j.cclet.2024.109697
18. [18]
  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
19. [19]
  Jiechen Liu , Xiaoguang Li , Ruiyang Xia , Yuqi Wang , Fenghe Zhang , Yongzhi Pang , Qing Li . Efficient suppression of oral squamous cell carcinoma through spatial dimension conversion drug delivery systems-enabled immunomodulatory-photodynamic therapy. Chinese Chemical Letters, 2024, 35(12): 109619-. doi: 10.1016/j.cclet.2024.109619
20. [20]
  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

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(753)
HTML views(6)

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