Nanocomplex hyaluronic acid/ganciclovir@ZIF-8 for ganciclovir efficient delivery and targeted anti-KSHV treatment
Abstract 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, G...
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BMC
2025-01-01
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| Series: | Cancer Nanotechnology |
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| Online Access: | https://doi.org/10.1186/s12645-024-00303-0 |
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| author | Fangling Li Chengjing Liu Wenyi Gu Qianhe Xu Dongmei Li Dongdong Cao Zhiyong Liu |
| author_facet | Fangling Li Chengjing Liu Wenyi Gu Qianhe Xu Dongmei Li Dongdong Cao Zhiyong Liu |
| author_sort | Fangling Li |
| collection | DOAJ |
| description | Abstract 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 Abstract |
| format | Article |
| id | doaj-art-4db3501b0a504cd09a49857ce77899b1 |
| institution | Kabale University |
| issn | 1868-6958 1868-6966 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Cancer Nanotechnology |
| spelling | doaj-art-4db3501b0a504cd09a49857ce77899b12025-01-05T12:08:44ZengBMCCancer Nanotechnology1868-69581868-69662025-01-0116112010.1186/s12645-024-00303-0Nanocomplex hyaluronic acid/ganciclovir@ZIF-8 for ganciclovir efficient delivery and targeted anti-KSHV treatmentFangling Li0Chengjing Liu1Wenyi Gu2Qianhe Xu3Dongmei Li4Dongdong Cao5Zhiyong Liu6School of Medicine, Key Laboratory of Xinjiang Endemic and Ethnic Diseases/International Science and Technology Cooperation Base of Xinjiang Endemic and Ethnic Diseases, Shihezi UniversitySchool of Medicine, Key Laboratory of Xinjiang Endemic and Ethnic Diseases/International Science and Technology Cooperation Base of Xinjiang Endemic and Ethnic Diseases, Shihezi UniversityAustralian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ)School of Chemistry and Molecular Engineering, East China University of Science and TechnologySchool of Medicine, Key Laboratory of Xinjiang Endemic and Ethnic Diseases/International Science and Technology Cooperation Base of Xinjiang Endemic and Ethnic Diseases, Shihezi UniversitySchool of Medicine, Key Laboratory of Xinjiang Endemic and Ethnic Diseases/International Science and Technology Cooperation Base of Xinjiang Endemic and Ethnic Diseases, Shihezi UniversitySchool of Chemistry and Chemical Engineering, Shihezi UniversityAbstract 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 Abstracthttps://doi.org/10.1186/s12645-024-00303-0Anti-KSHV treatmentGanciclovirDrug-carrying nanocomplexpH-responsive drug release |
| spellingShingle | Fangling Li Chengjing Liu Wenyi Gu Qianhe Xu Dongmei Li Dongdong Cao Zhiyong Liu Nanocomplex hyaluronic acid/ganciclovir@ZIF-8 for ganciclovir efficient delivery and targeted anti-KSHV treatment Cancer Nanotechnology Anti-KSHV treatment Ganciclovir Drug-carrying nanocomplex pH-responsive drug release |
| title | Nanocomplex hyaluronic acid/ganciclovir@ZIF-8 for ganciclovir efficient delivery and targeted anti-KSHV treatment |
| title_full | Nanocomplex hyaluronic acid/ganciclovir@ZIF-8 for ganciclovir efficient delivery and targeted anti-KSHV treatment |
| title_fullStr | Nanocomplex hyaluronic acid/ganciclovir@ZIF-8 for ganciclovir efficient delivery and targeted anti-KSHV treatment |
| title_full_unstemmed | Nanocomplex hyaluronic acid/ganciclovir@ZIF-8 for ganciclovir efficient delivery and targeted anti-KSHV treatment |
| title_short | Nanocomplex hyaluronic acid/ganciclovir@ZIF-8 for ganciclovir efficient delivery and targeted anti-KSHV treatment |
| title_sort | nanocomplex hyaluronic acid ganciclovir zif 8 for ganciclovir efficient delivery and targeted anti kshv treatment |
| topic | Anti-KSHV treatment Ganciclovir Drug-carrying nanocomplex pH-responsive drug release |
| url | https://doi.org/10.1186/s12645-024-00303-0 |
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