Citation: Jing REN, Jin-Hui YAN, An-Yi ZHANG, Yu-Xing YAN, Cun-Cun WANG, Lin LI. pH Regulated Nanomedicine Based on Y-Type Molecular Sieve Loading Doxorubicin: Preparation and Interaction with MM-231 Cells[J]. Chinese Journal of Inorganic Chemistry, ;2022, 38(1): 93-102. doi: 10.11862/CJIC.2022.019 shu

pH Regulated Nanomedicine Based on Y-Type Molecular Sieve Loading Doxorubicin: Preparation and Interaction with MM-231 Cells

Jing REN ^1,, ,
Jin-Hui YAN ¹ ,
An-Yi ZHANG ¹ ,
Yu-Xing YAN ¹ ,
Cun-Cun WANG ¹ ,
Lin LI ^{1, 2,,}

1.
Department of Chemistry, Taiyuan Normal University, Jinzhong, Shanxi 030619, China
2.
Humic Acid Engineering and Technology Research Center of Shanxi Province, Jinzhong, Shanxi 030619, China

Corresponding author: Jing REN, jing2008_1231@126.com Lin LI, lilin@tynu.edu.cn
Received Date: 14 July 2021
Revised Date: 19 October 2021

Figures(12)

To overcome the shortcomings of poor antitumor drug targeting, low efficacy, and high toxicity, a pH regulated drug delivery system (YMS-DOX) through hydrogen bonds and van der Waals force was constructed to acquire high drug loading capacity and better therapeutic efficiency based on Y-type molecular sieve (YMS) as nano-carrier and doxorubicin (DOX) as the model drug. The successful formation of YMS-DOX was confirmed by using UV-Vis, FT-IR, particle size and potential measurement, and fluorescence spectroscopy. Interestingly, with the assistance of citric acid buffer solution (pH=9.0), YMS nanocarrier loading DOX achieved nearly 99.61% loading efficiency. In vitro drug release showed that YMS had low premature drug release under physiological conditions (pH=7.4), while greatly enhanced in the tumor microenvironment (pH=4.5) 3.8 times compared to normal tissue, indicating YMSDOX can be effectively released in the tumor site. Excitingly, when dendritic (DC) cells and breast cancer (MM -231) cells were treated with YMS-DOX, the results demonstrated that YMS-DOX preferentially accumulated much more in tumor cells than in normal cells, which implies that YMS-DOX can selectively kill tumor cells. In addition, assessment by flow cytometry apoptosis assay illustrated that YMS-DOX could induce cell apoptosis and inhibit cell migration.
- Y-type molecular sieve,
- doxorubicin,
- pH regulating,
- high loading,
- breast cancer therapy
1. [1]
  Siegel R L, Miller K D, Jemal A. Cancer Statistics, 2019[J]. CA-CancerJ.Clin., 2019,69(1):7-34. doi: 10.3322/caac.21551
2. [2]
  Siegel R L, Miller K D, Jemal A. Cancer Statistics, 2020[J]. CA-CancerJ.Clin., 2020,70(1):7-30. doi: 10.3322/caac.21590
3. [3]
  Sethi A, Singh R P, Yadav N, Banerjee M. Synthesis, Spectroscopic Analysis (FT-IR, UV and NMR) and DFT Analysis of Novel Prodrugs of Pregnane, Their Apoptotic Activity in Cervical Cancer Cell Lines[J]. J.Mol. Struct., 2018,1166:54-62. doi: 10.1016/j.molstruc.2018.04.009
4. [4]
  CHEN B Y, ZHANG Y R, WANG L, WANG F F. Microwave Tomog-raphy for Early Breast Cancer Detection Based on the Alternating Direction Implicit Finite Difference Time-Domain Method[J]. Acta Phys.Sin., 2016,65(14):144101-144110. doi: 10.7498/aps.65.144101
5. [5]
  Li G C, Cao X Y, Li Y N, Qiu Y Y, Li Y N, Liu X J, Sun X X. MicroRNA-374b Inhibits Cervical Cancer Cell Proliferation and Induces Apopto-sis through the p38/ERK Signaling Pathway by Binding to JAM-2[J]. J.Cell. Physiol., 2018,233(9):7379-7390. doi: 10.1002/jcp.26574
6. [6]
  LI L, XU X R, LI Y Q, ZHANG C F. Preparation of Targeting Nanodi-amond-Metaminopterone Drug System and Its Interaction with MCF-7 Cells[J]. Chem. J. Chinese Universities, 2019,40(9):1998-2004.
7. [7]
  Hoffman A S. The Origins and Evolution of"Controlled"Drug Deliv-ery Systems[J]. J. Controlled Release, 2008,132(3):153-163. doi: 10.1016/j.jconrel.2008.08.012
8. [8]
  Langer R, Folkman J. Polymers for the Sustained Release of Proteins and Other Macromolecules[J]. Nature, 1976,263(5580):797-800. doi: 10.1038/263797a0
9. [9]
  Das M, Datir S R, Singh R P, Jain S. Augmented Anticancer Activity of a Targeted, Intracellularly Activatable, Theranostic Nanomedicine Based on Fluorescent and Radiolabeled, Methotrexate - Folic Acid -Multiwalled Carbon Nanotube Conjugate[J]. Mol. Pharmaceutics, 2013,10(7):2543-2557. doi: 10.1021/mp300701e
10. [10]
  Duncan B, Kim C, Rotello V M. Gold Nanoparticle Platforms as Drug and Biomacromolecule Delivery Systems[J]. J. Controlled Release, 2010,148(1):122-127. doi: 10.1016/j.jconrel.2010.06.004
11. [11]
  REN Y S, GUO Y Y, LIU X Y, SONG J, ZHANG C. Platinum (Ⅳ) Prodrug-Grafted Phosphorothioate DNA and Its Self-assembled Nanostructure for Targeted Drug Delivery[J]. Chem. J. Chinese Universi-ties, 2020,41(8):1721-1730.
12. [12]
  LIU D, ZHU X J, JIANG M, CHEN H, LAN S P. Synthesis and Anti-tumor Activities of 3-[(4'-Morpholine)-carbonyl or ethoxycarbonyl]-4-anilinoqunolines[J]. Chem. J. Chinese Universities, 2012,33(10):2249-2255. doi: 10.7503/cjcu20111217
13. [13]
  HUANG J, WANG D Y, LI S H, FAN H, FAN L Z. Red Fluorescent Carbon Quantum Dots for Diagnosis of Acidic Microenvironment in Tumors[J]. Acta Phys.-Chim. Sin., 2021,37(10)19050657.
14. [14]
  HAO W J, ZHANG J Q, SHANG Y Z, XU S H, LIU H L. Prepara-tion of Fluorescently Labeled pH - Sensitive Micelles for Controlled Drug Release[J]. Acta Phys.-Chim. Sin., 2016,32(10):2628-2635. doi: 10.3866/PKU.WHXB201606296
15. [15]
  YANG Z, XIE A J, SHEN Y H. pH - Controlled Drug Release of Nitrogen Doped Carbon Dots Delivering Doxorubicine for Synergetic Photo-Thermal Therapy and Chemotherapy[J]. Chinese J. Inorg. Chem., 2018,34(10):1775-1782. doi: 10.11862/CJIC.2018.236
16. [16]
  Wen Y, Wang Y Z, Liu X L, Zhang W, Xiong X H, Han Z X, Liang X J. Camptothecin-Based Nanodrug Delivery Systems[J]. Cancer Biol.Med., 2017,14(4):363-370. doi: 10.20892/j.issn.2095-3941.2017.0099
17. [17]
  Mochalin V N, Shenderova O, Ho D, Gogotsi Y. The Properties and Applications of Nanodiamonds[J]. Nat. Nanotechnol., 2012,7(1):11-23. doi: 10.1038/nnano.2011.209
18. [18]
  Wang Z Q, Tian Z M, Dong Y, Li L, Tian L, Li Y Q, Yang B S. Nanodiamond - Conjugated Transferrin as Chemotherapeutic Drug Delivery[J]. Diam. Relat. Mater., 2015,58:84-93. doi: 10.1016/j.diamond.2015.06.008
19. [19]
  Guan B, Zou F, Zhi J F. Nanodiamond as the pH-Responsive Vehicle for an Anticancer Drug[J]. Small, 2010,6(14):1514-1519. doi: 10.1002/smll.200902305
20. [20]
  Toh T B, Lee D K, Hou W X, Abdullah L N, Nguyen J, Ho D, Chow E K H. Nanodiamond-Mitoxantrone Complexes Enhance Drug Retention in Chemoresistant Breast Cancer Cells[J]. Mol. Pharmaceutics, 2014,11(8):2683-2691. doi: 10.1021/mp5001108
21. [21]
  Rao N V, Mane S R, Kishore A, Sarma J D, Shunmugam R. Norborn-ene Derived Doxorubicin Copolymers as Drug Carriers with pH Responsive Hydrazone Linker[J]. Biomacromolecules, 2012,13(1):221-230. doi: 10.1021/bm201478k
22. [22]
  Fan J Q, Fang G, Zeng F, Wang X D, Wu S Z. Water - Dispersible Fullerene Aggregates as a Targeted Anticancer Prodrug with Both Chemo - and Photodynamic Therapeutic Actions[J]. Small, 2013,9(4):613-621. doi: 10.1002/smll.201201456
23. [23]
  Vallet-Regi M, Ramila A, Del Real R P, Pérez-Pariente J. A New Property of MCM-41: Drug Delivery System[J]. Chem. Mater., 2001,13(2):308-311. doi: 10.1021/cm0011559
24. [24]
  Zhai Q Z. Preparation and Controlled Release of Mesoporous MCM-41/Propranolol Hydrochloride Composite Drug[J]. J. Microencapsul., 2013,30(2):173-180. doi: 10.3109/02652048.2012.714409
25. [25]
  Qin Q D, Xu Y. Enhanced Nitrobenzene Adsorption in Aqueous Solution by Surface Silylated MCM - 41[J]. Microporous MesoporousMater., 2016,232:143-150. doi: 10.1016/j.micromeso.2016.06.018
26. [26]
  Campos E V R, Oliveira J L D, Fraceto L F, Singh B. Polysaccha-rides as Safer Release Systems for Agrochemicals[J]. Agron. SustainableDev., 2015,35(1):47-66. doi: 10.1007/s13593-014-0263-0
27. [27]
  Rafi A A, Fakheri F, Mahkam M. Synthesis and Preparation of New pH-Sensitive Nanocomposite and Nanocapsule Based on"MCM-41/Poly Methacrylic Acid"as Drug Carriers[J]. Polym. Bull., 2016,73(10):2649-2659. doi: 10.1007/s00289-016-1627-1
28. [28]
  QU F Y, ZHU G S, HUANG S Y, LI S G, QIU S L. Preparation and Sustained Release of a New Water-Soluble Drug Carrier System Cap-topril/Si-MCM-41[J]. Chem. J. Chinese Universities, 2004,25(12):2195-2198. doi: 10.3321/j.issn:0251-0790.2004.12.001
29. [29]
  Arruebo M, Fernandez-Pacheco R, Irusta S, Arbiol J, Ibarra M R, Santamaria J. Sustained Release of Doxorubicin from Zeolite-Magnetite Nanocomposites Prepared by Mechanical Activation[J]. Nanotechnology, 2006,17:4057-4064. doi: 10.1088/0957-4484/17/16/011
30. [30]
  Yang F, Wen X, Ke Q F, Xie X T, Guo Y P. pH-Responsive Mesopo-rous ZSM - 5 Zeolites/Chitosan Core - Shell Nanodisks Loaded with Doxorubicin Against Osteosarcoma[J]. Mater. Sci. Eng. C, 2018,85:142-153. doi: 10.1016/j.msec.2017.12.024
31. [31]
  Wen X, Yang F, Ke Q F, Xie X T, Guo Y P. Hollow Mesoporous ZSM - 5 Zeolite/Chitosan Ellipsoids Loaded with Doxorubicin as pH-Responsive Drug Delivery Dystems Against Osteosarcoma[J]. J. Mater.Chem. B, 2017,5:7866-7876. doi: 10.1039/C7TB01830D
32. [32]
  Abasian P, Radmansouri M, Jouybari M H, Ghasemi M V, Moham-madi A, Irani M, Jazi F S. Incorporation of Magnetic NaX Zeolite/ DOX into the PLA/Chitosan Nanofibers for Sustained Release of Doxorubicin Against Carcinoma Cells Death In Vitro[J]. Int. J. Biol.Macromol., 2019,121:398-406. doi: 10.1016/j.ijbiomac.2018.09.215
33. [33]
  JIAO Y. Synthesis and Characterization of Self-Assembled Nano-Particle Mesozeolite Y. Taiyuan: Taiyuan University of Technology, 2019: 17-20
34. [34]
  Li L, Tian L, Wang Y L, Zhao W J, Cheng F Q, Li Y Q, Yang B S. Smart pH-Responsive and High Doxorubicin Loading Nanodiamond for In Vivo Selective Targeting, Imaging, and Enhancement of Anti-cancer Therapy[J]. J. Mater. Chem. B, 2016,4:5046-5058. doi: 10.1039/C6TB00266H
35. [35]
  Zhao W J, Wei S G, Zhao H M, Li Y Q, Wu R F, Wang J J. Enhanced Anticancer Activity of an Intracellularly Activatable Nanomedicine Based on GLYlated Nanodiamond[J]. Diam. Relat. Mater., 2017,77:171-180. doi: 10.1016/j.diamond.2017.07.003
36. [36]
  LI Y Q, ZHAO H M, ZHAO W J, WEI S G. Preparation of Enzyme-Responsive Nanodiamond Drug-Loading System and Its Endocytosis Mechanism by Cells[J]. Journal of Shanxi University(Natural ScienceEdition), 2017,40(3):533-539.
1. [1]
  Pei Li , Yuenan Zheng , Zhankai Liu , An-Hui Lu . Boron-Containing MFI Zeolite: Microstructure Control and Its Performance of Propane Oxidative Dehydrogenation. Acta Physico-Chimica Sinica, 2025, 41(4): 100034-. doi: 10.3866/PKU.WHXB202406012
2. [2]
  Shanghua Li , Malin Li , Xiwen Chi , Xin Yin , Zhaodi Luo , Jihong Yu . 基于高离子迁移动力学的取向ZnQ分子筛保护层实现高稳定水系锌金属负极的构筑. Acta Physico-Chimica Sinica, 2025, 41(1): 2309003-. doi: 10.3866/PKU.WHXB202309003
3. [3]
  Yuhao SUN , Qingzhe DONG , Lei ZHAO , Xiaodan JIANG , Hailing GUO , Xianglong MENG , Yongmei GUO . Synthesis and antibacterial properties of silver-loaded sod-based zeolite. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 761-770. doi: 10.11862/CJIC.20230169
4. [4]
  Jiali CHEN , Guoxiang ZHAO , Yayu YAN , Wanting XIA , Qiaohong LI , Jian ZHANG . Machine learning exploring the adsorption of electronic gases on zeolite molecular sieves. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 155-164. doi: 10.11862/CJIC.20240408
5. [5]
  Yiping HUANG , Liqin TANG , Yufan JI , Cheng CHEN , Shuangtao LI , Jingjing HUANG , Xuechao GAO , Xuehong GU . Hollow fiber NaA zeolite membrane for deep dehydration of ethanol solvent by vapor permeation. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 225-234. doi: 10.11862/CJIC.20240224
6. [6]
  Fei Xie , Chengcheng Yuan , Haiyan Tan , Alireza Z. Moshfegh , Bicheng Zhu , Jiaguo Yu . d带中心调控过渡金属单原子负载COF吸附O₂的理论计算研究. Acta Physico-Chimica Sinica, 2024, 40(11): 2407013-. doi: 10.3866/PKU.WHXB202407013
7. [7]
  Peng GENG , Guangcan XIANG , Wen ZHANG , Haichuang LAN , Shuzhang XIAO . Hollow copper sulfide loaded protoporphyrin for photothermal-sonodynamic therapy of cancer cells. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1903-1910. doi: 10.11862/CJIC.20240155
8. [8]
  Xingyang LI , Tianju LIU , Yang GAO , Dandan ZHANG , Yong ZHOU , Meng PAN . A superior methanol-to-propylene catalyst: Construction via synergistic regulation of pore structure and acidic property of high-silica ZSM-5 zeolite. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1279-1289. doi: 10.11862/CJIC.20240026
9. [9]
  Yuanpei ZHANG , Jiahong WANG , Jinming HUANG , Zhi HU . Preparation of magnetic mesoporous carbon loaded nano zero-valent iron for removal of Cr(Ⅲ) organic complexes from high-salt wastewater. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1731-1742. doi: 10.11862/CJIC.20240077
10. [10]
  Yufang GAO , Nan HOU , Yaning LIANG , Ning LI , Yanting ZHANG , Zelong LI , Xiaofeng LI . Nano-thin layer MCM-22 zeolite: Synthesis and catalytic properties of trimethylbenzene isomerization reaction. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1079-1087. doi: 10.11862/CJIC.20240036
11. [11]
  Jiarong Feng , Yejie Duan , Chu Chu , Dezhen Xie , Qiu'e Cao , Peng Liu . Preparation and Application of a Streptomycin Molecularly Imprinted Electrochemical Sensor: A Suggested Comprehensive Analytical Chemical Experiment. University Chemistry, 2024, 39(8): 295-305. doi: 10.3866/PKU.DXHX202401016
12. [12]
  Di WU , Ruimeng SHI , Zhaoyang WANG , Yuehua SHI , Fan YANG , Leyong ZENG . Construction of pH/photothermal dual-responsive delivery nanosystem for combination therapy of drug-resistant bladder cancer cell. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1679-1688. doi: 10.11862/CJIC.20240135
13. [13]
  Jingwen Wang , Minghao Wu , Xing Zuo , Yaofeng Yuan , Yahao Wang , Xiaoshun Zhou , Jianfeng Yan . Advances in the Application of Electrochemical Regulation in Investigating the Electron Transport Properties of Single-Molecule Junctions. University Chemistry, 2025, 40(3): 291-301. doi: 10.12461/PKU.DXHX202406023
14. [14]
  Peiling Li , Qing Feng , Hongling Yuan , Qin Wang . Live Interview Recording about the Penicillin Family. University Chemistry, 2024, 39(9): 122-127. doi: 10.3866/PKU.DXHX202311022
15. [15]
  Faqiong Zhao , Xiaohang Qiu , Yanping Ren , Juanjuan Song , Dongcheng Liu , Xiuqiong Zeng , Wenwei Zhang , Mei Shi , Min Hu , Wan Li , Yongxian Fan , Yiru Wang , Xiuyun Wang , Weihong Li , Yong Fan , Jianrong Zhang , Shuyong Zhang . The Use of pH Indicator Papers and pH Meters. University Chemistry, 2025, 40(5): 32-39. doi: 10.12461/PKU.DXHX202503099
16. [16]
  Zhongxin YU , Wei SONG , Yang LIU , Yuxue DING , Fanhao MENG , Shuju WANG , Lixin YOU . Fluorescence sensing on chlortetracycline of a Zn-coordination polymer based on mixed ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2415-2421. doi: 10.11862/CJIC.20240304
17. [17]
  Kexin Dong , Chuqi Shen , Ruyu Yan , Yanping Liu , Chunqiang Zhuang , Shijie Li . Integration of Plasmonic Effect and S-Scheme Heterojunction into Ag/Ag₃PO₄/C₃N₅ Photocatalyst for Boosted Photocatalytic Levofloxacin Degradation. Acta Physico-Chimica Sinica, 2024, 40(10): 2310013-. doi: 10.3866/PKU.WHXB202310013
18. [18]
  Weikang Wang , Yadong Wu , Jianjun Zhang , Kai Meng , Jinhe Li , Lele Wang , Qinqin Liu . Green H₂O₂ synthesis via melamine-foam supported S-scheme Cd_0.5Zn_0.5In₂S₄/S-doped carbon nitride heterojunction: synergistic interfacial charge transfer and local photothermal effect. Acta Physico-Chimica Sinica, 2025, 41(8): 100093-0. doi: 10.1016/j.actphy.2025.100093
19. [19]
  Kai PENG , Xinyi ZHAO , Zixi CHEN , Xuhai ZHANG , Yuqiao ZENG , Jianqing JIANG . Progress in the application of high-entropy alloys and high-entropy ceramics in water electrolysis. Chinese Journal of Inorganic Chemistry, 2025, 41(7): 1257-1275. doi: 10.11862/CJIC.20240454
20. [20]
  Di ZHANG , Tianxiang XIE , Xu HE , Wanyu WEI , Qi FAN , Jie QIAO , Gang JIN , Ningbo LI . Construction and antitumor activity of pH/GSH dual-responsive magnetic nanodrug. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 786-796. doi: 10.11862/CJIC.20240329

Get Citation

PDF

XML

Metrics

PDF Downloads(15)
Abstract views(1611)
HTML views(443)

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