Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Fangling Li,Dongdong Cao,Lixia Yao,Wenyi Gu,Zhiyong Liu,Dongmei Li,Lin Cui
Kaposi’s sarcoma-associated herpesvirus (KSHV) can infect a variety of cells and cause malignant tumors. At present, the use of microRNA (miRNA) for anti-KSHV is a promising treatment strategy, but the instability and non-specific uptake of miRNA still limit its use in the treatment of KSHV. In the present study, we constructed a nano-drug delivery system employing chemical grafting and electrostatic adsorption to solve the problems of easy degradation and low cell uptake of miRNA during direct administration. This nano-drug delivery system is to graft 4-carboxyphenylboric acid (PBA) and lauric acid (LA) onto polyethylenimine (PEI) through amidation reaction, and then prepare cationic copolymer nanocarriers (LA-PEI-PBA). The drug-carrying nanocomplex LA-PEI-PBA/miR-34a-5p was formed after further electrostatic adsorption of miR-34a-5p on the carrier and could protect miR-34a-5p from nuclease and serum degradation. Modification of the drug-carrying nanocomplex LA-PEI-PBA/miR-34a-5p by targeted molecule PBA showed effective uptake, increase in the level of miR-34a-5p, and inhibition of cell proliferation and migration in KSHV-infected cells. In addition, the drug-carrying nanocomplex could also significantly reduce the expression of KSHV lytic and latent genes, achieving the purpose of anti-KSHV treatment. In conclusion, these cationic copolymer nanocarriers with PBA targeting possess potential applications in nucleic acid delivery and anti-KSHV therapy.
研究领域:
药学
·
分子生物学
·
纳米技术
·
病毒学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 5
·2932
·
IF 4.9
Fangling Li,Dongdong Cao,Wenyi Gu,Dongmei Li,Zhiyong Liu,Lin Cui
Kaposi’s sarcoma-associated herpesvirus (KSHV) can cause a variety of malignancies. Ganciclovir (GCV) is one of the most efficient drugs against KSHV, but its non-specificity can cause other side effects in patients. Nucleic acid miR-34a-5p can inhibit the transcription of KSHV RNA and has great potential in anti-KSHV therapy, but there are still problems such as easy degradation and low delivery efficiency. Here, we constructed a co-loaded dual-drug nanocomplex (GCV@ZIF-8/PEI-FA+miR-34a-5p) that containsGCVinternally and adsorbs miR-34a-5p externally. The folic acid (FA)-coupled polyethyleneimine (PEI) coating layer (PEI-FA) was shown to increase the cellular uptake of the nanocomplex, which is conducive to the enrichment of drugs at the KSHV infection site.GCVand miR-34a-5p are released at the site of the KSHV infection through the acid hydrolysis characteristics of ZIF-8 and the “proton sponge effect” of PEI. The co-loaded dual-drug nanocomplex not only inhibits the proliferation and migration of KSHV-positive cells but also decreases the mRNA expression level of KSHV lytic and latent genes. In conclusion, this co-loaded dual-drug nanocomplex may provide an attractive strategy for antiviral drug delivery and anti-KSHV therapy.
研究领域:
药理学
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纳米技术
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病毒学
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分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cancer Nanotechnology
·
2025
·Vol. 16
·期 1
·1-20
·
IF 4.8
Li Fangling,Liu Chengjing,Gu Wenyi,Xu Qianhe,Li Dongmei,Cao Dongdong,Liu Zhiyong
Kaposi's sarcoma-associated herpesvirus (KSHV) infection can cause a variety of tumors and is one of the leading causes of death in acquired immune deficiency syndrome (AIDS) patients. As a small molecule antiviral drug, ganciclovir (GCV) can be used for anti-KSHV treatment. However, GCV has non-specific action and toxic side effects in vivo, and how to make it safer and more effective against KSHV is still a great challenge. By encapsulating GCV into metal–organic skeleton material zeolitic imidazolate framework-8 (ZIF-8) and further modification of hyaluronic acid (HA), the nanomedical delivery system of GCV (HA/GCV@ZIF-8) has been developed for efficient GCV delivery and targeted anti-KSHV treatment. The modification of HA leads to the targeted binding of the nanocomplex with the overexpressed CD44 receptors in tumor cell membranes, resulting in the increased accumulation and cellular uptake of GCV. Exploiting the decomposition property of ZIF-8 under acidic conditions, the nanocomplex exhibits pH-responsive drug release in slightly acidic tumor environment. In addition, HA/GCV@ZIF-8 not only suppresses expression of KSHV pathogenic genes with less drug dose, but also inhibits the ability of cell proliferation and migration. In vivo anti-tumor results showed that HA/GCV@ZIF-8 accumulated in tumor cells and effectively inhibited tumor growth. The results open a gate for the targeted anti-KSHV treatment. Graphical
研究领域:
医学
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药学
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病毒学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 23
·12946
·
IF 4.9
Chengjing Liu,Xiuyuan Yin,Huiling Xu,Jianyu Xu,Mengru Gong,Zhenzhong Li,Qianhe Xu,Dongdong Cao,Dongmei Li
Kaposi’s sarcoma-associated herpesvirus (KSHV) is a variety of the human gamma-herpesvirus that often leads to the occurrence of malignant tumors. In addition, the occurrence of Kaposi’s sarcoma is a major cause of death among AIDS patients. Ganciclovir (GCV) is the most widely used drug against KSHV infection in the clinic. GCV can restrict the in vivo synthesis of DNA polymerase in KSHV, thereby inhibiting the replication of the herpesvirus. However, GCV still suffers from poor specificity and transmembrane capabilities, leading to many toxic side effects. Therefore, developing a drug delivery system that increases GCV concentrations in target cells remains a significant clinical challenge. In this study, zeolite imidazole salt framework-8 (ZIF-8), a biocompatible porous material constructed by coordinating zinc ions and 2-methylimidazole, was used to load GCV. A nano-delivery system with a microneedle structure was also constructed using a polydimethylsiloxane (PDMS) microneedle mold to fabricate MN/GCV@ZIF-8 arrays. These arrays not only offered good skin-piercing capabilities but also significantly inhibited the cleavage and replication of the virus in vivo, exerting an anti-KSHV function. For these reasons, the arrays were able penetrate the skin’s stratum corneum at the tumor site to deliver GCV and play an anti-KSHV role.
研究领域:
药学
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纳米技术
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病毒学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-9
·
IF 5.228
Hu Linzhen,Zhu Hucheng,Li Lei,Huang Jinfeng,Sun Weiguang,Liu Junjun,Li Hua,Luo Zengwei,Wang Jianping,Xue Yongbo,Zhang Yu,Zhang Yonghui
Two pairs of new enantiomers with unusual 5,5-spiroketal cores, termed (±)-japonones A and B [(±)- 1 and (±)- 2 ], were obtained from Hypericum japonicum Thunb. The absolute configurations of (±)- 1 and (±)- 2 were characterized by extensive analyses of spectroscopic data and calculated electronic circular dichroism (ECD) spectra, the application of modified Mosher’s methods and the assistance of quantum chemical predictions (QCP) of 13 C NMR chemical shifts. Among these metabolites, (+)- 1 exhibited some inhibitory activity on Kaposi’s sarcoma associated herpesvirus (KSHV). Virtual screening of (±)- 1 and (±)- 2 were conducted using the Surflex-Dock module in the Sybyl software and (+)- 1 exhibited ability to bind with ERK to form key interactions with residues Lys52, Pro56, Ile101, Asp165, Gly167 and Val99.
研究领域:
植物化学
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病毒学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Fangling Li,Dongdong Cao,Wenyi Gu,Lin Cui,Zhongpeng Qiu,Zhiyong Liu,Dongmei Li,Xuhong Guo
Kaposi’s sarcoma-associated herpesvirus (KSHV) infection can cause a range of malignancies. The use of microRNA (miRNA) to combat viruses and inhibit tumor development has received increasing attention. However, it is difficult for free miRNA to enter into cells directly and to degrade easily. Therefore, the miRNA therapy alone often fails to achieve the expected effect. The selection of an appropriate delivery system for effective miRNA delivery and anti-KSHV is rarely considered. In this study, a β-cyclodextrin-grafted polyethylenimine (β-CD-PEI) was prepared by the chemical synthesis method, and folic acid was further coupled to a nanocarrier (β-CD-PEI-FA). Gel electrophoresis retardation experiments showed that β-CD-PEI-FA could combine with miR-34a-5p to form a drug-carrying nanocomplex β-CD-PEI-FA/miR-34a-5p, which effectively protected miR-34a-5p from serum and nuclease degradation. The particle size and potential were 203.13 ± 0.41 nm and 27.02 ± 0.72 mV, respectively, which were suitable for endocytosis. The cytotoxicity of the vector to KSHV-positive cells BCBL-1 and SK-RG cells was detected by the CCK-8 assay, which proved that the vector had good biosafety in vitro. Further cell experiments showed that β-CD-PEI-FA/miR-34a-5p not only had the ability to transport miR-34a-5p but also accelerated the G2-phase process of BCBL-1 and SK-RG cells and inhibited the proliferation of KSHV-infected cells. Most importantly, it can significantly reduce the expression levels of KSHV genes ORF26, K8.1A, and LANA. Therefore, the nanocarriers may be a promising antiviral drug delivery system with potential applications in the anti-KSHV therapy.
研究领域:
药学
·
分子生物学
·
病毒学
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）