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Bioactive Materials · 2021 · IF 14.593

Virus-inspired surface-nanoengineered antimicrobial liposome: A potential system to simultaneously achieve high activity and selectivity

Yin Shi,Xiaoqian Feng,Liming Lin,Jing Wang,Jiaying Chi,Biyuan Wu,Guilin Zhou,Feiyuan Yu,Qian Xu,Daojun Liu,Guilan Quan,Chao Lu,Xin Pan,Jianfeng Cai,Chuanbin Wu

Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity. Since simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches, we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side effects. Herein, a surface-nanoengineered antimicrobial liposome (SNAL) is developed with the morphological features of enveloped viruses, including a moderate size range, lipid-based membrane structure, and highly lipopeptide-enriched bilayer surface. The SNAL possesses virus-like infection to bacterial cells, which can mediate high-efficiency and high-selectivity bacteria binding, rapidly attack and invade bacteria via plasma membrane fusion pathway, and induce a local “burst” release of lipopeptide to produce irreversible damage of cell membrane. Remarkably, viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations (1.6–6.3 μg mL −1 ), high bactericidal efficiency of >99% within 2 h, >10-fold enhanced selectivity over free lipopeptide, 99.8% reduction in skin MRSA load after a single treatment, and negligible toxicity. This bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials.

研究领域: 生物医学工程 · 药剂学 · 微生物学
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Materials Today Bio · 2025 · IF 10.2

CD44-targeted virus-mimicking nanomedicine eliminates cancer stem cells and mitigates chemoresistance in head and neck squamous cell carcinoma

Yiwen Chen,Zhen Qin,Yujia Wang,Baoxin Gu,Jing Wang,Yunfei Zheng,Yuting Niu,Lingfei Jia

Cancer stem cells (CSCs) play critical roles in tumor growth, metastasis, and chemoresistance. Although several small-molecule inhibitors designed to inhibit CSCs have been investigated in clinical trials, their inadequate tumor targeting and potential off-target side effects have led to poor outcomes. A CD44-targeted virus-mimicking nanomedicine encapsulating the BMI1 inhibitor PTC209 (PTC209@VNP-HA) was designed to treat head and neck squamous cell carcinoma (HNSCC). We used a dendritic mesoporous silica nanoparticle (MSN) as the core for virus-mimicking nanoparticle (VNP) formation after adding shell particles to the MSN surface. The VNP surface was then modified with hyaluronic acid (HA), and PTC209 was adsorbed by mesopores to form PTC209@VNP-HA. In this system, HA is used to target CD44 + CSCs. The rough surface of VNP-HA provided better drug delivery efficiency than smooth nanoparticles modified with HA. VNP-HA enhanced the cancer inhibitory effect of PTC209 12-fold compared to the administration of free PTC209, leading to significantly higher bioavailability of PTC209. Both in vitro and in vivo assays showed that PTC209@VNP-HA inhibited cancer stemness, proliferation, and metastasis in HNSCC. Mechanistically, this inhibitory effect is closely associated with DNA damage/apoptosis signaling. Using a series of preclinical models in murine systems, we confirmed that PTC209@VNP-HA eliminated BMI1 + CSCs, and greatly inhibited the proliferation and metastasis of HNSCC when combined with cisplatin.This study investigated PTC209@VNP-HA as a novel and potentially transformative HNSCC treatment option that eliminates CSCs, prevents metastasis, and overcomes cisplatin resistance.

CAS / MDL: 112-02-7 102-71-6
研究领域: 肿瘤学 · 纳米医学 · 分子生物学
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ACS Nano · 2023 · IF 17.1

Virus Mimetic Framework DNA as a Non-LNP Gene Carrier for Modulated Cell Endocytosis and Apoptosis

Qian Shi,Yuanyuan Wu,Yunyun Xu,Min Bao,Xiao Chen,Kui Huang,Qiulan Yang,Yang Yang

Mimicking the size and shape of spherical viruses, we constructed a soccer-ball shaped virus-inspired DNA origami (ViDO) framework as a programmable non-LNP (lipid nanoparticle) gene carrier. The DNA framework was decorated with precisely controlled recognition molecules outside and loaded with adequate genetic molecules inside. Five variants were constructed to systematically investigate their cell uptake and modulated gene silencing efficiency. Cellular uptake was enhanced with an increasing number of aptamers, while with a median number of aptamer supply, dispersed distribution performed better than the clustered pattern. Intriguingly, the transfection efficiency was maximized using the ViDO with clustered five aptamers, which exhibited a competitive RNA silencing effect induced by Lipo2000 with low cytotoxicity. Our results revealed the effects of aptamer distribution patterns on endocytosis and transfection, thus providing a programmable platform for meticulous optimization of the gene delivery system.

CAS / MDL: 128446-34-4
研究领域: 分子生物学 · 纳米技术 · 基因工程 · 生物医学工程
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