Citation: Lin LI, Jiaxue LI, Meixia YANG, Jiayu DING, Jiaqi JING, Ruiping ZHANG. Preparation of mitoxantrone self-assembled carrier-free nanodrugs regulated by sodium acetate for apoptosis induction of human breast carcinoma cells[J]. Chinese Journal of Inorganic Chemistry, ;2025, 41(12): 2536-2548. doi: 10.11862/CJIC.20250138 shu

Preparation of mitoxantrone self-assembled carrier-free nanodrugs regulated by sodium acetate for apoptosis induction of human breast carcinoma cells

Lin LI ^{1, 2,,} ,
Jiaxue LI ¹ ,
Meixia YANG ¹ ,
Jiayu DING ¹ ,
Jiaqi JING ¹ ,
Ruiping ZHANG ^2,,

1.
College of Chemistry and Materials, Taiyuan Normal University, Jinzhong, Shanxi 030619, China
2.
The Radiology Department of Shanxi Provincial People′s Hospital, Shanxi Medical University, Taiyuan 030012, China

Corresponding author: Lin LI, lilin@tynu.edu.cn Ruiping ZHANG, zrp_7142@sxmu.edu.cn
Received Date: 22 April 2025
Revised Date: 29 September 2025

Figures(11)

Based on the hydrogen bonding self-assembly strategy, a sodium acetate (NaAc) regulated high loading carrier-free nanodrug (MIT-DOX/NaAc, MIDA) was fabricated by employing a nano-coprecipitation method, which used mitoxantrone (MIT) and doxorubicin (DOX) as antitumor drug models. MIDA successfully formed with a maximum loading efficiency (95%), and the in vitro drug release showed that MIDA is pH-responsive. Excitingly, cytotoxicity and scratch migration assessments demonstrated that MIDA could target tumor cells through the enhanced permeability and retention effect (EPR), subsequently inhibiting the migration and proliferation of human breast carcinoma cells (MCF-7). The efficacy was higher than that of free DOX, MIT, and DOX/NaAc. Examination by fluorescence microscopy and flow cytometry showed that the uptake of MIDA by MCF-7 was time-dependent. In addition, MIDA could enter MCF-7 via both the clathrin and caveolae co-mediated endocytosis pathways, and then the dissociated MIT and DOX migrated into the nucleus to induce MCF-7 late apoptosis.
- mitoxantrone,
- carrier-free nanodrug,
- sodium acetate regulation,
- hydrogen bond self-assembly,
- human breast carcinoma cells
1. [1]
  SIEGEL R L, GIAQUINTO A N, JEMAL A. Cancer statistics, 2024[J]. CA-Cancer J. Clin., 2024,74(1):12-49. doi: 10.3322/caac.21820
2. [2]
  WU H, LÜ Q. Epidemiological trends and implications of breast cancer prevention and control in China and the world: An interpretation of the Global Cancer Statistics Report 2018-2022[J]. Chinese J. Bases Clin. Gen. Surg., 2024,31(7):796-802.
3. [3]
  HAN B F, ZHENG R S, ZENG H M, WANG S M, SUN K X, CHEN R, LI L, WEI W Q, HE J. Cancer incidence and mortality in China, 2022[J]. J. Natl. Cancer Cent., 2024,4(1):47-53.
4. [4]
  LU Z H, CHEN Y, LIU D, JIAO X, LIU C, WANG Y K, ZHANG Z Z, JIA K, GONG J F, YANG Z M, SHEN L. The landscape of cancer research and cancer care in China[J]. Nat. Med., 2023,29:3022-3032. doi: 10.1038/s41591-023-02655-3
5. [5]
  LI L, XU X R, LI Y Q, ZHANG C F. Preparation of targeting nanodiamond-metaminopterone drug system and its interaction with MCF-7 cells[J]. Chem. J. Chinese Universities, 2019,40(9):1998-2004.
6. [6]
  YAO H Z, WANG Z G, WANG N, DENG Z Q, LIU G Y, ZHOU J H, CHEN S, SHI J H, ZHU G Y. Enhancing circulation and tumor accumulation of carboplatin via an erythrocyte-anchored prodrug strategy[J]. Angew. Chem. ‒Int. Edit., 2022,61(25)e202203838. doi: 10.1002/anie.202203838
7. [7]
  WINTER J O. One step closer to cancer nanomedicine[J]. Science, 2022,377(6604):371-372. doi: 10.1126/science.add3666
8. [8]
  BHATIA S N, CHEN X Y, DOBROVOLSKAIA M A, LAMMERS T. Cancer nanomedicine[J]. Nat. Rev. Cancer, 2022,22:550-556. doi: 10.1038/s41568-022-00496-9
9. [9]
  CAI S S, LI T Y, AKINADE T, ZHU Y F, LEONG K W. Drug delivery carriers with therapeutic functions[J]. Adv. Drug Delivery Rev., 2021,176113884. doi: 10.1016/j.addr.2021.113884
10. [10]
  MEI H, CAI S S, HUANG D, GAO H L, CAO J, HE B. Carrier-free nanodrugs with efficient drug delivery and release for cancer therapy: From intrinsic physicochemical properties to external modification[J]. Bioact. Mater., 2022,8:220-240.
11. [11]
  LIU T, LI L X, WANG S, DONG F D, ZUO S Y, SONG J X, WANG X, LU Q, WANG H L, ZHANG H T, CHENG M S, LIU X H, HE Z G, SUN B J, SUN J. Hybrid chalcogen bonds in prodrug nanoassemblies provides dual redox-responsivity in the tumor microenvironment[J]. Nat Commun., 2022,137228. doi: 10.1038/s41467-022-35033-7
12. [12]
  XIE X, JIANG K L, LI B W, HOU S L, TANG H L, SHAO B H, PING Y, ZHANG Q Q. A small-molecule self-assembled nanodrug for combination therapy of photothermal-differentiation-chemotherapy of breast cancer stem cells[J]. Biomaterials, 2022,286121598. doi: 10.1016/j.biomaterials.2022.121598
13. [13]
  WANG H, LIN F, WU Y, GUO W, CHEN X S, XIAO C S, CHEN M W. Carrier-free nanodrug based on co-assembly of methylprednisolone dimer and rutin for combined treatment of spinal cord injury[J]. ACS Nano, 2023,17(13):12176-12187. doi: 10.1021/acsnano.3c00360
14. [14]
  YU M Y, YU J J, ZHOU Y J, LIANG Z, TANG H, LI C B, QUE Q Y, WANG H X, XIE H Y, XU X. A self-assembled nanomicelle-based "one stone for two birds" strategy for precision therapy of hepatic ischemia-reperfusion injury[J]. Nano Res., 2025,18(2)94907185. doi: 10.26599/NR.2025.94907185
15. [15]
  XU Y D, CHEN Z J, HAO W, YANG Z M, FARAG M, VONG C T, WANG Y T, WANG S P. Berberine and magnolol exert cooperative effects on ulcerative colitis in mice by self-assembling into carrier-free nanostructures[J]. J Nanobiotechnol., 2024,22538. doi: 10.1186/s12951-024-02804-x
16. [16]
  TIAN J H, CHEN K, ZHANG Q, QIU C, TONG H B, HUANG J N, HAO M J, CHEN J H, ZHAO W T, WONG Y K, GAO L, LUO P, WANG J G, DU Q F. Mechanism of self-assembled celastrol-erianin nanomedicine for treatment of breast cancer[J]. Chem. Eng. J., 2024,499155709. doi: 10.1016/j.cej.2024.155709
17. [17]
  FANG F, CHEN X. Carrier-free nanodrugs: From bench to bedside[J]. ACS Nano, 2024,18(35):23827-23841. doi: 10.1021/acsnano.4c09027
18. [18]
  AN J L, ZHANG Z Q, ZHANG J R, ZHANG L Y, LIANG G F. Research progress in tumor therapy of carrier-free nanodrug[J]. Biomed. Pharmacother., 2024,178117258. doi: 10.1016/j.biopha.2024.117258
19. [19]
  LI L, TIAN H L, ZHANG Z, DING N, HE K, LU S J, LIU R L, WU P J, WANG Y, HE B, LUO M C, PENG P L, YANG M, NICE E C, HUANG C H, XIE N, WANG D, GAO W. Carrier-free nanoplatform via evoking pyroptosis and immune response against breast cancer[J]. ACS Appl. Mater. Interfaces, 2023,15(1):452-468. doi: 10.1021/acsami.2c17579
20. [20]
  YAO Y Q, XU Z N, DING H R, YANG S S, CHEN B H, ZHOU M J, ZHU Y H, YANG A H, YAN X X, LIANG C R, KOU X D, CHEN B, HUANG W, LI Y B. Carrier-free nanoparticles-new strategy of improving druggability of natural products[J]. J. Nanobiotechnol., 2025,23108. doi: 10.1186/s12951-025-03146-y
21. [21]
  DONG X R, LIU H, LIU H B, ZHANG X Q, DENG X R. Carrier-free nanomedicines: Mechanisms of formation and biomedical applications[J]. Giant, 2024,18100256. doi: 10.1016/j.giant.2024.100256
22. [22]
  ZHANG H J, CHEN W J, WANG J, DU W X, WANG B B, SONG L, HU Y, MA X P. A novel ROS-activable self-immolative prodrug for tumor-specific amplification of oxidative stress and enhancing chemotherapy of mitoxantrone[J]. Biomaterials, 2023,293121954. doi: 10.1016/j.biomaterials.2022.121954
23. [23]
  ZHANG R J, GUO L H, LI Q J, LIANG Y, LIAO Y Y, XU H B, LIU C T, ZHOU G D, WANG L, XU S X, YUAN M M. Biodegradable carrier-free nanomedicine via self-assembly of pure drug molecules for triple sensitization of radiotherapy[J]. ACS Nano, 2025,19(17):16355-16371. doi: 10.1021/acsnano.4c15736
24. [24]
  XU X D, WANG G W, CHEN Y J, JIN P L, CHEN J F, FANG X, YE D Q, HUANG P T. Ultrasound-activated carrier-free nanoprodrugs enhanced universality and efficiency of solid tumor-targeting chemotherapy[J]. Bioact. Mater., 2025,50:571-584.
25. [25]
  SU Q Y, WANG Z Y, ZHOU H M, ZHANG M M, DENG W J, WEI X, XIAO J S, DUAN X P. Eradication of large tumors by nanoscale drug self-assembly[J]. Adv. Mater., 2024,36(49)2410536. doi: 10.1002/adma.202410536
26. [26]
  ZHANG B W, LI L X, HUANG M L, ZHAO E W, LI Y Q, SUN J, HE Z G, FU C W, LIU G J, SUN B J. Probing the impact of surface functionalization module on the performance of mitoxantrone prodrug nanoassemblies: Improving the effectiveness and safety[J]. Nano Lett., 2024,24(12):3759-3767. doi: 10.1021/acs.nanolett.4c00300
27. [27]
  LI H, ZHANG X L, CHEN S T, CAO C, ZHANG X, LI X, XING S X, JIA S T, LI J S, WANG S. Hypoxia exacerbation-triggered doxorubicin prodrug activation for sequential photodynamic/chemotherapy[J]. ACS Mater. Lett., 2024,6(7):2599-2608. doi: 10.1021/acsmaterialslett.4c00798
28. [28]
  LE Z C, CHEN Y T, HAN H H, TIAN H K, ZHAO P F, YANG C B, HE Z Y, LIU L X, LEONG K W, MAO H Q, LIU Z J, CHEN Y M. Hydrogen-bonded tannic acid-based anticancer nanoparticle for enhancement of oral chemotherapy[J]. ACS Appl. Mater. Interfaces, 2018,10(49):42186-42197. doi: 10.1021/acsami.8b18979
29. [29]
  YANG Z T, SHI X Z, QIU L Y. Tunable supramolecular self-assemblies based on cyclodextrin polymer as a loading platform for water-soluble drugs[J]. Carbohydr. Polym., 2025,347122743. doi: 10.1016/j.carbpol.2024.122743
30. [30]
  ZHANG J X, FANG H K, DAI Y B, LI Y Q, LI L X, ZUO S Y, LIU T, SUN Y X, SHI X B, HE Z G, SUN J, SUN B J. Cholesterol sulfate-mediated ion-pairing facilitates the self-nanoassembly of hydrophilic cationic mitoxantrone[J]. J. Colloid Interface Sci., 2024,669:731-739. doi: 10.1016/j.jcis.2024.05.029
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