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自组装红花多糖纳米颗粒作为肝细胞癌增强治疗的靶向药物递送系统

 

Authors Bai H, Yang J, Zhang J, Wang R

Received 3 June 2025

Accepted for publication 30 September 2025

Published 5 November 2025 Volume 2025:20 Pages 13333—13358

DOI https://doi.org/10.2147/IJN.S544439

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Kamakhya Misra

Haotian Bai,1,* Jing Yang,2,* Junhao Zhang,1 Rui Wang1,3 

1College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150040, People’s Republic of China; 2College of Basic Medical Science, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150040, People’s Republic of China; 3Key Laboratory of Basic and Application Research of Beiyao, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin, Heilongjiang, 150040, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Rui Wang, College of Pharmacy, Heilongjiang University of Chinese Medicine, 24 Heping Road, Xiangfang District, Harbin, Heilongjiang, 150040, People’s Republic of China, Tel +8613101669321, Fax +451 87266893, Email wrdx@sina.com

Purpose: Bone morphogenetic protein 7 (BMP7) plays a crucial role in the pathogenesis of hepatocellular carcinoma (HCC). Traditional therapies have severe side effects and cannot achieve the desired therapeutic effect. Delivery of small interfering RNA targeting BMP7 (siBMP7) can specifically down-regulate the expression of BMP7 and induce apoptosis of cancer cells, thereby achieving the effect of gene therapy. We aimed to use cationic safflower polysaccharide (SPS) as the basic carrier, and encapsulate it with synthetic hyaluronic acid (HA) and folic acid (FA) polymer to form a dual-targeting nano-carrier. After encapsulating siBMP7, we obtain dual-targeted self-assembled nanoparticles (NPs). This not only improves the delivery efficiency, maintains stability in the blood circulation, and enhances accumulation in the tumor site, but also achieves the effect of gene therapy for HCC.
Methods: We identified SPS, and then prepared and characterized the self-assembled NPs modified with polyethyleneimine (PEI), which can target the HA receptors and FA receptors on the surface of SMMC-7721 cells and deliver siBMP7 to hepatoma cells and induce cell apoptosis. The temperature stability, serum stability, cytotoxicity, buffering capacity, hemolytic properties, release behavior, uptake ability, and gene silencing effect of the NPs were evaluated in vitro. Further evaluation of their in vivo distribution, therapeutic effect, and safety was conducted in a nude rats model.
Results: The HA-FA polymer is light yellow and has strong water solubility. The blank NPs and self-assembled NPs have uniform particle size, physical stability, and stable release ability. HFSPNPs showed strong uptake ability and apoptotic effect in SMMC-7721 cells and LO2 cells. HFSPNPs could relatively effectively accumulate in the liver of rats and down-regulate the expression of BMP7 to induce apoptosis of hepatoma cells. Pathological analysis showed that the safety of HFSPNPs is better.
Conclusion: HFSPNPs have better tumor targeting properties, enabling siBMP7 to accumulate more in the tumor tissue and be released, thereby promoting apoptosis of hepatoma cells. This indicates that their potential for treating HCC is equivalent to that of gene therapy. This study highlights the potential of cationic SPS as a drug delivery material.

Keywords: dual-target, safflower polysaccharide, hepatocellular carcinoma, self-assembled nanoparticles