Work

Synaptic vesicle protein 2-targeted doxorubicin-loaded liposome for effective neuroblastoma therapy

Year: 2024

Type: article

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. • Neuroblastoma (NB) cells overexpress synaptic vesicle protein 2 (SV2). • New drug engineered by coupling SV2-targeting botulinum toxin domain to doxorubicin liposome. • Targeted liposome delivers doxorubicin effectively, inducing apoptosis in NB cells. • Novel drug shows potent anti-NB effects with minimal side effects in mice. • Innovative coupling strategy has potential for broader cancer therapy applications

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2024.117548