Citation: 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[J]. Chinese Journal of Inorganic Chemistry, ;2025, 41(4): 786-796. doi: 10.11862/CJIC.20240329 shu

Construction and antitumor activity of pH/GSH dual-responsive magnetic nanodrug

Di ZHANG ¹ ,
Tianxiang XIE ² ,
Xu HE ¹ ,
Wanyu WEI ¹ ,
Qi FAN ¹ ,
Jie QIAO ¹ ,
Gang JIN ^3,, ,
Ningbo LI ^1,,

1.
School of Basic Medical Sciences, Shanxi Medical University, Taiyuan 030001, China
2.
School of Stomatology, Shanxi Medical University, Taiyuan 030001, China
3.
Department of Radiation Oncology, Second Hospital of Shanxi Medical University, Taiyuan 030001, China

Corresponding author: Gang JIN, jingang2018@sina.com Ningbo LI, ningboli@sxmu.edu.cn
Received Date: 9 September 2024
Revised Date: 5 January 2025

Figures(9)

Herein, a mesoporous magnetic nanocarrier containing disulfide bonds (NH₂-SMNPs) was developed to improve the efficacy of tumor treatment and reduce side effects. After loading the carrier with doxorubicin (DOX), a nontoxic pullulan oxide was used as a gating material to form the oSMNPs/DOX nanodrug. This nanodrug exhibited uniform dispersion, good drug-loading capacity, and high saturation magnetization, enabling pH/glutathione (GSH) dual-responsive drug release in the tumor microenvironment, with a release rate as high as 81.53%. Furthermore, this nanodrug demonstrated good biocompatibility, effective capability to kill cancer cells, and competent cellular uptake ability.
- magnetic materials,
- mesoporous silica,
- pH/GSH dual-responsive
1. [1]
  HALBROOK C J, LYSSIOTIS C A, PASCA DI MAGLIANO M, MAITRA A. Pancreatic cancer: Advances and challenges[J]. Cell, 2023,186(8):1729-1754. doi: 10.1016/j.cell.2023.02.014
2. [2]
  ALHODIEB F S, BARKAT M A, BARKAT H A, AB HADI H, KHAN M I, ASHFAQ F, RAHMAN M A, HASSAN M Z, ALANEZI A A. Chitosan-modified nanocarriers as carriers for anticancer drug delivery: Promises and hurdles[J]. Int. J. Biol. Macromol., 2022,217:457-469.
3. [3]
  FENG X Y, LI F S, ZHANG L L, LIU W M, WANG X P, ZHU R, QIAO Z A, YU B, YU X H. TRAIL-modified, doxorubicin-embedded periodic mesoporous organosilica nanoparticles for targeted drug delivery and efficient antitumor immunotherapy[J]. Acta Biomater., 2022,143:392-405. doi: 10.1016/j.actbio.2022.03.001
4. [4]
  JOSEPH M M, RAMYA A N, VIJAYAN V M, NAIR J B, BASTIAN B T, PILLAI R K, THERAKATHINAL S T, MAITI K K. Targeted theranostic nano vehicle endorsed with self-destruction and immunostimulatory features to circumvent drug resistance and wipe-out tumor reinitiating cancer stem cells[J]. Small, 2020,16(38)2003309. doi: 10.1002/smll.202003309
5. [5]
  WANG T Y, LEI H L, LI X, YANG N L, MA C, LI G Q, GAO X, GE J, LIU Z, CHENG L, CHEN G. Magnetic targeting nanocarriers combined with focusing ultrasound for enhanced intracerebral hemorrhage therapy[J]. Small, 2023,19(17)2206982. doi: 10.1002/smll.202206982
6. [6]
  CHEN D Y, LIU X C, LU X Y, TIAN J W. Nanoparticle drug delivery systems for synergistic delivery of tumor therapy[J]. Front. Pharmacol., 2023,141111991.
7. [7]
  ŽIVOJEVIĆ K, MLADENOVIĆ M, DJISALOV M, MUNDZIC M, RUIZ-HERNANDEZ E, GADJANSKI I, KNEŽEVIĆ N Ž. Advanced mesoporous silica nanocarriers in cancer theranostics and gene editing applications[J]. J. Control. Release, 2021,337:193-211.
8. [8]
  FERNANDES N B, NAYAK Y, GARG S, NAYAK U Y. Multifunctional engineered mesoporous silica/inorganic material hybrid nanoparticles: Theranostic perspectives[J]. Coord. Chem. Rev., 2023,478214977.
9. [9]
  VALLET-REGÍ M, SCHÜTH F, LOZANO D, COLILLA M, MANZANO M. Engineering mesoporous silica nanoparticles for drug delivery: Where are we after two decades[J]. Chem. Soc. Rev., 2022,51(13):5365-5451. doi: 10.1039/D1CS00659B
10. [10]
  SANCHO-ALBERO M, ROSSO G, DE COLA L, CAUDA V. Cargo-loaded lipid-shielded breakable organosilica nanocages for enhanced drug delivery[J]. Nanoscale, 2023,15(35):14628-14640. doi: 10.1039/D3NR02155F
11. [11]
  ZHOU S, ZHONG Q, WANG Y, HU P, ZHONG W, HUANG C B, YU Z Q, DING C D, LIU H X, FU J J. Chemically engineered mesoporous silica nanoparticles-based intelligent delivery systems for theranostic applications in multiple cancerous/non-cancerous diseases[J]. Coord. Chem. Rev., 2022,452214309. doi: 10.1016/j.ccr.2021.214309
12. [12]
  JIANG Z Y, ZHANG M H, LI P F, WANG Y, FU Q R. Nanomaterial-based CT contrast agents and their applications in image-guided therapy[J]. Theranostics, 2023,13(2):483-509. doi: 10.7150/thno.79625
13. [13]
  KUMARI R, NARVI S, DUTTA P. Synthesis of chitosan succinate-g-amine functionalized mesoporous silica: Inorganic-organic nanohybrid for antibacterial assessment, antioxidant activity and pH-controlled drug delivery[J]. Int. J. Biol. Macromol., 2023,234123763. doi: 10.1016/j.ijbiomac.2023.123763
14. [14]
  LEE T H, MOGHADAM F, JUNG J G, KIM Y J, ROH J S, YOO S Y, LEE B K, KIM J H, PINNAU I, PARK H B. In situ derived hybrid carbon molecular sieve membranes with tailored ultramicroporosity for efficient gas separation[J]. Small, 2021,17(47)2104698.
15. [15]
  FENG Y, LIAO Z, LI M Y, ZHANG H X, LI T T, QIN X, LI S, WU C H, YOU F M, LIAO X L, CAI L L, YANG H, LIU Y Y. Mesoporous silica nanoparticles-based nanoplatforms: Basic construction, current state, and emerging applications in anticancer therapeutics[J]. Adv. Healthc. Mater., 2023,12(16)2201884.
16. [16]
  ZENG X W, LIU G, TAO W, MA Y, ZHANG X D, HE F, PAN J M, MEI L, PAN G Q. A drug-self-gated mesoporous antitumor nanoplatform based on pH-sensitive dynamic covalent bond[J]. Adv. Funct. Mater., 2017,27(11)1605985.
17. [17]
  WU L, LV R H, WANG H H, GAO S S, WANG Y, ZHANG S S, ZHOU H Y, AN Y L, CAO M Z, JI Y S. Facile fabrication of glutathione-responsive and photothermal nanocarriers with dendritic mesoporous silica nanoparticles for the controlled drug delivery[J]. J. Nanopart. Res., 2022,24128.
18. [18]
  LI X L, CHEN Y Y, ZHANG X, ZHAO Y B. Fabrication of biodegradable auto-fluorescent organosilica nanoparticles with dendritic mesoporous structures for pH/redox-responsive drug release[J]. Mater. Sci. Eng. C‒Mater. Biol. Appl., 2020,112110914.
19. [19]
  WANG Y Y, SHAHI P K, WANG X X, XIE R S, ZHAO Y, WU M, ROGE S, PATTNAIK B R, GONG S. In vivo targeted delivery of nucleic acids and CRISPR genome editors enabled by GSH-responsive silica nanoparticles[J]. J. Control. Release, 2021,336:296-309.
20. [20]
  NAZARI F S M, PANAHI H A, JAHANMARDI R. Construction of a dual stimuli-responsive drug delivery platform based on the copper sulfide nanoparticles modified N-isopropyl acrylamide/allyl acetoacetate for docetaxel delivery: In vitro release and kinetic studies[J]. Inorg. Chem. Commun., 2023,156111230.
21. [21]
  SINGH R K, PATEL K D, MAHAPATRA C, PARTHIBAN S P, KIM T H, KIM H W. Combinatory cancer therapeutics with nanoceria-capped mesoporous silica nanocarriers through pH- triggered drug release and redox activity[J]. ACS Appl. Mater. Interfaces, 2019,11(1):288-299.
22. [22]
  YANG Z F, WANG L H, LIU Y, LIU S M, TANG D J, MENG L, CUI B. ZnO capped flower-like porous carbon-Fe₃O₄ composite as carrier for bi-triggered drug delivery[J]. Mater. Sci. Eng. C‒Mater. Biol. Appl., 2020,107110256.
23. [23]
  GARCÍA-FERNÁNDEZ A, AZNAR E, MARTÍNEZ-MÁÑEZ R, SANCENON F. New advances in vivo applications of gated mesoporous silica as drug delivery nanocarriers[J]. Small, 2020,16(3)1902242.
24. [24]
  ZHOU X, HE X, DONG Z Y, WANG Y X, HU C Q, ZHANG D, GUO R, QIAO J, LI N B. Manganese-doped mesoporous magnetic nanocarriers for cancer treatment[J]. ACS Appl. Nano Mater., 2024,7(6):6339-6350.
25. [25]
  BULATAO B P, NALINRATANA N, JANTARATANA P, VAJRAGUPTA O, ROJSITTHISAK P, ROJSITTHISAK P. Lutein-loaded chitosan/alginate-coated Fe₃O₄ nanoparticles as effective targeted carriers for breast cancer treatment[J]. Int. J. Biol. Macromol., 2023,242124673.
26. [26]
  SELVAKUMAR G, LONCHIN S. Fabrication and characterization of collagen-oxidized pullulan scaffold for biomedical applications[J]. Int. J. Biol. Macromol., 2020,164:1592-1599.
27. [27]
  PATIL S B, INAMDAR S Z, DAS K K, AKAMANCHI K G, PATIL A V, INAMADAR A C, REDDY K R, RAGHU A V, KULKARNI R V. Tailor-made electrically-responsive poly(acrylamide)-graft-pullulan copolymer based transdermal drug delivery systems: Synthesis, characterization, in-vitro and ex-vivo evaluation[J]. J. Drug Deliv. Sci. Technol., 2020,56101525.
28. [28]
  DAI Z D, WEN W, GUO Z M, SONG X Z, ZHENG K, XU X Y, QI X Y, TAN Z Q. SiO₂-coated magnetic nano-Fe₃O₄ photosensitizer for synergistic tumour-targeted chemo-photothermal therapy[J]. Colloid Surf. B‒Biointerfaces, 2020,195111274.
29. [29]
  FUJII Y, ZHOU S J, SHIMADA M, KUBO M. Synthesis of monodispersed hollow mesoporous organosilica and silica nanoparticles with controllable shell thickness using soft and hard templates[J]. Langmuir, 2023,39(13):4571-4582.
30. [30]
  QI G Q, WANG S C, YIN Q Q, ZHANG Z C, WEN X C, HAO L G. A pH-responsive nanoplatform based on magnetic mesoporous silica nanoparticles for enhanced treatment of pancreatic cancer[J]. ACS Appl. Nano Mater., 2023,6(24):23184-23195.
31. [31]
  SONG S H, LI X Y, JI Y S, LV R H, WU L, WANG H H, CAO M Z, XU Z G. GSH/pH dual-responsive and HA-targeting nano-carriers for effective drug delivery and controlled release[J]. J. Drug Deliv. Sci. Technol., 2021,62102327.
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