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Dual-aptamer-decorated reduction-activated dimeric-prodrug nanoparticles for broad-spectrum treatment of leukemia
Shan Yang1, Riming Wang1, Mei Liu2
1Department of Pharmacy, the General Hospital of Eastern Command of the Chinese People's Liberation Army (PLA), Nanjing 210012, China.
Abstract:
Leukemia remains a fatal disease for most affected patients, and a simple and effective therapeutic strategy is urgently needed. Targeted delivery chemo-drugs to leukemia cells shows promise, but the diverse subtypes of leukemia make single-ligand nanomedicine often ineffective. Herein, a dual-aptamer decorated, reduction-responsive dimeric prodrug-based nanoparticle (NP), termed SXP-NPs, was developed using the two leukemia-specific aptamers Sgc8c and XQ-2d, a reduction-responsive podophyllotoxin (POD) dimeric prodrug, and DSPE-PEG2000. Because the receptors of XQ-2d (CD71) and Sgc8c (PTK7) are overexpressed in different subtypes of leukemia cells, SXP-NPs can broadly and selectively recognize these leukemia cells after intravenous administration, subsequently releasing POD in response to the intracellular high-reduction environment to kill the leukemia cells. In vitro experiments showed that these simple SXP-NPs can specifically bind to various leukemia cancer cells and kill them. In vivo experiments revealed that SXP-NPs can remarkably reduce spleen weight, decrease white blood cell counts, and extend overall survival in a preclinical leukemia animal model. The in vitro and in vivo validation demonstrated that SXP-NPs offer several advantages, including high drug-loading potential, broad-spectrum recognition of leukemia cells, reduced systemic toxicity, and enhanced therapeutic effects of the drug. Taken together, this study provides a simple and effective strategy for broad-spectrum leukemia therapy and highlights the clinical potential of SXP-NPs.
Insights
A novel dual-aptamer nanoparticle (SXP-NP) therapy shows promise for broad-spectrum leukemia treatment. These nanoparticles target diverse leukemia cells and deliver a potent drug, improving survival rates in preclinical models.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Oncology
Background:
- Leukemia is a fatal disease requiring new therapies.
- Targeted drug delivery faces challenges due to leukemia subtype diversity.
- Current single-ligand nanomedicines are often ineffective against various leukemia types.
Purpose of the Study:
- To develop a dual-aptamer decorated, reduction-responsive nanoparticle (SXP-NP) for broad-spectrum leukemia therapy.
- To enhance targeted drug delivery and therapeutic efficacy against diverse leukemia subtypes.
- To evaluate the in vitro and in vivo performance of SXP-NPs in a preclinical leukemia model.
Main Methods:
- Development of SXP-NPs using leukemia-specific aptamers (Sgc8c, XQ-2d), a dimeric prodrug (POD), and DSPE-PEG2000.
- In vitro assessment of SXP-NP binding specificity and cytotoxicity against various leukemia cell lines.
- In vivo evaluation of SXP-NP efficacy in a preclinical leukemia animal model, measuring spleen weight, white blood cell count, and survival.
Main Results:
- SXP-NPs demonstrated broad and selective recognition of diverse leukemia cells.
- In vitro studies confirmed specific binding and killing of leukemia cancer cells.
- In vivo studies showed significant reduction in spleen weight, decreased white blood cell counts, and extended survival in a leukemia animal model.
Conclusions:
- SXP-NPs offer a simple and effective strategy for broad-spectrum leukemia therapy.
- The dual-aptamer design enhances recognition of diverse leukemia subtypes.
- SXP-NPs exhibit high drug-loading, reduced systemic toxicity, and improved therapeutic outcomes, highlighting clinical potential.
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