Preparation and in vitro validation of nanotransmission system for accurate targeting of CD24 high-expression triple negative breast cancer cells

doi:10.12307/2023.452

Chinese Journal of Tissue Engineering Research ›› 2023, Vol. 27 ›› Issue (25): 4013-4019.doi: 10.12307/2023.452

Preparation and in vitro validation of nanotransmission system for accurate targeting of CD24 high-expression triple negative breast cancer cells

Zhou Yuqing1, 2, Li Jinsui2, 3, Chen Yu1, 2, Chen Maoshan4, Hou Lingmi2, 3, Wang Dongsheng4, Pu Lulan1, 2, Deng Shishan2, Zhou Fangfang1, 2

1Department of Anatomy, School of Basic Medicine and Forensics, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China; 2Biological Targeting Laboratory of Breast Cancer, Academician (Expert) Workstation, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China; 3Department of Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China; 4Department of Breast and Thyroid Surgery, Affiliated Suining Central Hospital of Chongqing Medical University, Suining 629000, Sichuan Province, China

Received:2022-04-13 Accepted:2022-06-22 Online:2023-09-08 Published:2023-01-17
Contact: Zhou Fangfang, Master, Lecturer, Department of Anatomy, School of Basic Medicine and Forensics, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China; Biological Targeting Laboratory of Breast Cancer, Academician (Expert) Workstation, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China Deng Shishan, PhD, Professor, Biological Targeting Laboratory of Breast Cancer, Academician (Expert) Workstation, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
About author:Zhou Yuqing, Master candidate, Department of Anatomy, School of Basic Medicine and Forensics, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China; Biological Targeting Laboratory of Breast Cancer, Academician (Expert) Workstation, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China Li Jinsui, Master, Attending physician, Biological Targeting Laboratory of Breast Cancer, Academician (Expert) Workstation, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China; Department of Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Supported by:
the City and School Cooperation Innovation Team Project of Nanchong in 2020, No. 20SXCXTD0001 (to HLM); the Administration of Traditional Chinese Medicine Scientific Research Project of Sichuan Province, No. 2020JC0055 (to HLM); the Municipal School Science and Technology Strategic Cooperation Project of Nanchong Municipal Science and Technology Bureau, No. 20SXQT0052 (to ZFF); 2022 Open Experimental Project of North Sichuan Medical College, No. SY22-060 (to ZFF); 2022 Scientific Research and Development Program of Affiliated Hospital of North Sichuan Medical College, No. 2022JC004 (to LJS)

Abstract

Abstract: BACKGROUND: The combination of nanotechnology and medicine has opened up a new path in the field of selective targeting and tumor treatment. Through the application of nano carriers, the targeted delivery and stability of loaded drugs are ensured, and the cell uptake and biocompatibility are enhanced.
OBJECTIVE: To prepare a glutathione and pH double-responsive CD24 aptamer-modified nanodrug delivery system PC (coBP) Ca for ferroptosis agonists Erastin and biplasmids and to investigate its precise targeting and feasibility of CD24 highly expressed cells in triple negative breast cancer in vitro.
METHODS: PEG-CAPDB underwent multiple polymerization reactions to form a nanosphere skeleton called: COOH-PEG-CPADB-[co BMA co PDSMA], and then PC (coBP) formation by self-assembling synthesis of the internally loaded ferroptosis agonist Erastin, 1-2M2ge compound, NF2 knockout plasmid and YAP overexpressed plasmid. SELEX technology was used to screen CD24 aptamers to further modify PC (CoBP). Nano-drug delivery system PC (coBP) Ca was eventually formed. The effects of CD24 aptamer modification on the surface of PC(coBP)Ca, sensitivity to glutathione and pH, phagocytosis and targeting properties of immune cells escaping, lysosomal escaping phagocytosis and drug burst release properties, and phagocytosis of phagocytes were detected.
RESULTS AND CONCLUSION: The average particle size of PC (coBP) Ca was (141.11±13.43) nm. The average polydispersity index was (0.353±0.074). The average Zeta potential showed good dispersibility. The average drug loading of Erastin was (23.34±2.45)%. The encapsulation rate of PC (coBP) Ca was (90.24±3.11)%, and the 4-hour release was about 90% under the dual response system of glutathione and pH, which could effectively evade immune cell phagocytosis to accurately target CD24 highly expressed triple negative breast cancer, escape lysosomes, then achieve drug release, which activates the ferroptosis pathway and promotes phagocyte phagocytosis. The successful synthesis of nano-delivery system PC (coBP) Ca has the characteristics of precision, effectiveness, safety and low toxicity, and is expected to become a CD24 high-expression cell-targeted nano-delivery system in triple negative breast cancer.

Key words: triple negative breast cancer, nano-delivery system, ferroptosis, CD24, targeted drug delivery, glutathione

CLC Number:

Zhou Yuqing, Li Jinsui, Chen Yu, Chen Maoshan, Hou Lingmi, Wang Dongsheng, Pu Lulan, Deng Shishan, Zhou Fangfang. Preparation and in vitro validation of nanotransmission system for accurate targeting of CD24 high-expression triple negative breast cancer cells[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(25): 4013-4019.

Figures/Tables 4

References

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Preparation and in vitro validation of nanotransmission system for accurate targeting of CD24 high-expression triple negative breast cancer cells

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