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Novel nano-pomegranates based on astragalus polysaccharides for targeting ERα-positive breast cancer and multidrug
Bingjie Wang1, Chunjing Guo1, Yanhui Liu2
1School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, P.R. China.
Abstract:
Chemotherapy is an important method for treating breast cancer. However, multidrug resistance is one of the major challenges in breast cancer chemotherapy. There is an urgent need to develop novel, effective antitumor strategies that will perfect existing therapeutic regimens. In this study, the double-targeted nanocarrier, Quercetin-3'3-dithiodipropionic acid-Astragalus polysaccharides-Folic acid (QDAF), was successfully synthesized and self-assembled into a neoteric nano-targeted delivery strategy, named nano-pomegranates, and which were utilized to effectively inhibit multidrug resistance in estrogen receptor α (ERα)-positive breast tumor. The outstanding abilities of nano-pomegranates to release the drug in a reducing environment was determined by in vitro release assay. The cellular studies in MCF-7 cells were examined that nano-pomegranates have remarkable efficiencies of enhancing cellular uptake, inhibition and necrosis and apoptosis. In vivo antitumor experiments showed that nano-pomegranates have better anti-tumor effects and lower systemic toxicity than free Cur. In conclusion, nano-pomegranates have great potential in anti-breast cancer treatment.
Insights
This study introduces novel nano-pomegranates to combat multidrug resistance in breast cancer. These nanocarriers effectively deliver drugs, enhancing treatment efficacy and reducing toxicity for estrogen receptor α-positive tumors.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Multidrug resistance (MDR) poses a significant challenge in breast cancer chemotherapy.
- Developing novel strategies to overcome MDR is crucial for improving therapeutic outcomes.
- Estrogen receptor α (ERα)-positive breast tumors are a major subtype requiring targeted treatments.
Purpose of the Study:
- To synthesize and characterize a novel double-targeted nanocarrier (QDAF) for breast cancer treatment.
- To evaluate the efficacy of the self-assembled 'nano-pomegranates' in overcoming multidrug resistance.
- To assess the *in vitro* and *in vivo* performance of nano-pomegranates in ERα-positive breast tumor models.
Main Methods:
- Synthesis and self-assembly of Quercetin-3'3-dithiodipropionic acid-Astragalus polysaccharides-Folic acid (QDAF) into nano-pomegranates.
- Evaluation of drug release kinetics in a reducing environment using *in vitro* assays.
- Cellular studies using MCF-7 cells to assess cellular uptake, inhibition, necrosis, and apoptosis.
- *In vivo* antitumor experiments in relevant animal models to determine anti-tumor effects and systemic toxicity.
Main Results:
- Nano-pomegranates demonstrated effective drug release in a reducing environment.
- Enhanced cellular uptake, inhibition, necrosis, and apoptosis were observed in MCF-7 cells treated with nano-pomegranates.
- *In vivo* studies showed superior anti-tumor effects and reduced systemic toxicity compared to free Curcumin (Cur).
Conclusions:
- Nano-pomegranates represent a promising targeted delivery strategy for overcoming multidrug resistance in breast cancer.
- The developed nanocarrier system exhibits significant potential for enhancing the efficacy of breast cancer chemotherapy.
- This novel approach offers a viable strategy to improve treatment outcomes for ERα-positive breast tumors.
