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Published on: February 9, 2019
Self-Assembled Safflower Polysaccharide Nanoparticles as a Targeted Drug Delivery System for Enhanced Therapy of
Haotian Bai1, Jing Yang2, Junhao Zhang1
1College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150040, People's Republic of China.
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.
