Peptidyl Virus-Like Nanovesicles as Reconfigurable "Trojan Horse" for Targeted siRNA Delivery and Synergistic Inhibition of Cancer Cells.
Zixuan WangDongzhao HaoYuefei WangJinwu ZhaoJiaxing ZhangXi RongJiaojiao ZhangJiwei MinWei QiRongxin SuMingxia HePublished in: Small (Weinheim an der Bergstrasse, Germany) (2022)
The self-assembly of peptidyl virus-like nanovesicles (pVLNs) composed of highly ordered peptide bilayer membranes that encapsulate the small interfering RNA (siRNA) is reported. The targeting and enzyme-responsive sequences on the bilayer's surface allow the pVLNs to enter cancer cells with high efficiency and control the release of genetic drugs in response to the subcellular environment. By transforming its structure in response to the highly expressed enzyme matrix metalloproteinase 7 (MMP-7) in cancer cells, it helps the siRNA escape from the lysosomes, resulting in a final silencing efficiency of 92%. Moreover, the pVLNs can serve as reconfigurable "Trojan horse" by transforming into membranes triggered by the MMP-7 and disrupting the cytoplasmic structure, thereby achieving synergistic anticancer effects and 96% cancer cell mortality with little damage to normal cells. The pVLNs benefit from their biocompatibility, targeting, and enzyme responsiveness, making them a promising platform for gene therapy and anticancer therapy.
Keyphrases
- cancer therapy
- gene therapy
- high efficiency
- drug delivery
- induced apoptosis
- oxidative stress
- cell cycle arrest
- cell migration
- cardiovascular events
- risk factors
- cardiovascular disease
- stem cells
- copy number
- bone marrow
- type diabetes
- dna methylation
- endoplasmic reticulum stress
- gene expression
- coronary artery disease
- cell therapy
- tissue engineering