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Synaptic vesicle protein 2-targeted doxorubicin-loaded liposome for effective neuroblastoma therapy
Yang Liu1, Dongya Zhang1, Miaomiao Kong1
1School of Life Sciences, Henan University, Kaifeng 475001, China.
Abstract:
Neuroblastoma, a pediatric cancer originating from neural crest tissues of the sympathetic nervous system, poses significant treatment challenges due to its molecular diversity and restricted druggable targets. While chemotherapy is a common treatment, its drawbacks, including poor targeting of cancer cells and nonspecific cytotoxicity, highlight the urgent need for innovative and effective therapeutic strategies. Herein, we developed a novel drug by coupling the receptor binding domain of botulinum neurotoxin type A (Hc) fused with monomeric streptavidin (mSA) to biotin coated doxorubicin (Dox)-loaded liposome, via interaction between mSA and biotin. The resultant Hc-coated liposome (Hc-Lipo@Dox) actively targeted the recycling synaptic vesicle 2 protein (SV2) abundantly expressed on the surface of neuroblastoma cells. Our results revealed that Hc-Lipo@Dox more effectively entered the neuroblastoma SH-SY5Y cells, inducing apoptosis compared to non-targeted liposome and free Dox. Moreover, Hc-Lipo@Dox rapidly enriched Dox in the subcutaneously implanted neuroblastoma tumor in nude mice, resulting potent anti-neuroblastoma effect compared to non-targeted liposomes or free Dox. Importantly, Hc-Lipo@Dox significantly improved the survival rate of treated mice, while also exhibiting a favorable safety profile with no discernible impact on mobility or observable side effects. These findings highlight the potential of SV2-targeted Dox liposome as a promising and well-tolerated chemotherapy approach for neuroblastoma treatment. Moreover, the technology established here has broader applications for various cancer therapies by substituting the Hc moiety with other tumor-specific targeting moieties.
Insights
A novel liposome drug targets neuroblastoma by binding to SV2 receptors. This targeted chemotherapy effectively kills cancer cells, reduces tumor size in mice, and improves survival rates with minimal side effects.
Area of Science:
- Oncology
- Nanotechnology
- Biochemistry
Background:
- Neuroblastoma presents treatment challenges due to molecular diversity and limited drug targets.
- Conventional chemotherapy for neuroblastoma has limitations, including poor targeting and systemic toxicity.
- There is a critical need for advanced therapeutic strategies with improved efficacy and safety.
Purpose of the Study:
- To develop and evaluate a novel drug delivery system for neuroblastoma treatment.
- To create a targeted liposome utilizing botulinum neurotoxin type A (Hc) and monomeric streptavidin (mSA) for enhanced neuroblastoma cell uptake.
- To assess the efficacy and safety of the Hc-coated doxorubicin-loaded liposome (Hc-Lipo@Dox) in preclinical models.
Main Methods:
- Conjugation of the Hc-mSA complex to biotin-coated doxorubicin (Dox)-loaded liposomes.
- In vitro evaluation of Hc-Lipo@Dox uptake and apoptosis induction in neuroblastoma SH-SY5Y cells.
- In vivo assessment of Hc-Lipo@Dox tumor accumulation, anti-tumor efficacy, survival rate, and safety in neuroblastoma-bearing nude mice.
Main Results:
- Hc-Lipo@Dox demonstrated enhanced cellular uptake and apoptosis induction in neuroblastoma cells compared to non-targeted liposomes and free Dox.
- Significant accumulation of Dox within neuroblastoma tumors was observed with Hc-Lipo@Dox in vivo.
- Hc-Lipo@Dox exhibited potent anti-neuroblastoma effects, significantly improved survival rates, and a favorable safety profile in mice.
Conclusions:
- SV2-targeted Dox liposomes represent a promising and well-tolerated chemotherapy approach for neuroblastoma.
- The developed Hc-Lipo@Dox system shows significant potential for improving neuroblastoma treatment outcomes.
- This targeted drug delivery technology has broader applicability for other cancer types by modifying the targeting moiety.
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