Study of siRNA Delivery via Polymeric Nanoparticles in Combination with Angiogenesis Inhibitor for The Treatment of <i>AFP</i>-Related Liver Cancer
Angiogenesis inhibitor drugs have been explored as important pharmacological agents for cancer therapy, including hepatocellular carcinoma. These agents have several drawbacks, such as drug resistance, nonspecific toxicity, and systemic side effects. Therefore, combination therapy of the drug and sm...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/20/12666 |
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| author | Kittiporn Punuch Chamaiphorn Wongwan Saranrat Jantana Chayapol Somboonyosdech Kamonlatth Rodponthukwaji Natsuda Kunwong Kytai T. Nguyen Vorapan Sirivatanauksorn Yongyut Sirivatanauksorn Chatchawan Srisawat Primana Punnakitikashem |
| author_facet | Kittiporn Punuch Chamaiphorn Wongwan Saranrat Jantana Chayapol Somboonyosdech Kamonlatth Rodponthukwaji Natsuda Kunwong Kytai T. Nguyen Vorapan Sirivatanauksorn Yongyut Sirivatanauksorn Chatchawan Srisawat Primana Punnakitikashem |
| author_sort | Kittiporn Punuch |
| collection | DOAJ |
| description | Angiogenesis inhibitor drugs have been explored as important pharmacological agents for cancer therapy, including hepatocellular carcinoma. These agents have several drawbacks, such as drug resistance, nonspecific toxicity, and systemic side effects. Therefore, combination therapy of the drug and small interfering RNA could be a promising option to achieve high therapeutic efficacy while allowing a lower systemic dose. Therefore, we studied adding an alpha-fetoprotein siRNA (<i>AFP</i>-siRNA) incorporated on polymeric nanoparticles (NPs) along with angiogenesis inhibitor drugs. The <i>AFP</i> siRNA-loaded NPs were successfully synthesized at an average size of 242.00 ± 2.54 nm. Combination treatment of <i>AFP</i>-siRNA NPs and a low dose of sunitinib produced a synergistic effect in decreasing cell viability in an in vitro hepatocellular carcinoma (HCC) model. <i>AFP</i>-siRNA NPs together with sorafenib or sunitinib greatly inhibited cell proliferation, showing only 39.29 ± 2.72 and 44.04 ± 3.05% cell viability, respectively. Moreover, quantitative reverse transcription PCR (qRT-PCR) demonstrated that <i>AFP</i>-siRNA incorporated with NPs could significantly silence <i>AFP</i>-mRNA expression compared to unloaded NPs. Interestingly, the expression level of <i>AFP</i>-mRNA was further decreased to 28.53 ± 5.10% when sunitinib was added. Therefore, this finding was considered a new promising candidate for HCC treatment in reducing cell proliferation and enhancing therapeutic outcomes. |
| first_indexed | 2024-03-09T20:04:44Z |
| format | Article |
| id | doaj.art-5b40f421425043f2a9fb152433833f85 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:04:44Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5b40f421425043f2a9fb152433833f852023-11-24T00:35:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201266610.3390/ijms232012666Study of siRNA Delivery via Polymeric Nanoparticles in Combination with Angiogenesis Inhibitor for The Treatment of <i>AFP</i>-Related Liver CancerKittiporn Punuch0Chamaiphorn Wongwan1Saranrat Jantana2Chayapol Somboonyosdech3Kamonlatth Rodponthukwaji4Natsuda Kunwong5Kytai T. Nguyen6Vorapan Sirivatanauksorn7Yongyut Sirivatanauksorn8Chatchawan Srisawat9Primana Punnakitikashem10Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandDepartment of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandDepartment of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandDepartment of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandResearch Network NANOTEC—MU in Theranostic Nanomedicine, Bangkok 10700, ThailandResearch Network NANOTEC—MU in Theranostic Nanomedicine, Bangkok 10700, ThailandDepartment of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USADepartment of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandDepartment of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandDepartment of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandDepartment of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ThailandAngiogenesis inhibitor drugs have been explored as important pharmacological agents for cancer therapy, including hepatocellular carcinoma. These agents have several drawbacks, such as drug resistance, nonspecific toxicity, and systemic side effects. Therefore, combination therapy of the drug and small interfering RNA could be a promising option to achieve high therapeutic efficacy while allowing a lower systemic dose. Therefore, we studied adding an alpha-fetoprotein siRNA (<i>AFP</i>-siRNA) incorporated on polymeric nanoparticles (NPs) along with angiogenesis inhibitor drugs. The <i>AFP</i> siRNA-loaded NPs were successfully synthesized at an average size of 242.00 ± 2.54 nm. Combination treatment of <i>AFP</i>-siRNA NPs and a low dose of sunitinib produced a synergistic effect in decreasing cell viability in an in vitro hepatocellular carcinoma (HCC) model. <i>AFP</i>-siRNA NPs together with sorafenib or sunitinib greatly inhibited cell proliferation, showing only 39.29 ± 2.72 and 44.04 ± 3.05% cell viability, respectively. Moreover, quantitative reverse transcription PCR (qRT-PCR) demonstrated that <i>AFP</i>-siRNA incorporated with NPs could significantly silence <i>AFP</i>-mRNA expression compared to unloaded NPs. Interestingly, the expression level of <i>AFP</i>-mRNA was further decreased to 28.53 ± 5.10% when sunitinib was added. Therefore, this finding was considered a new promising candidate for HCC treatment in reducing cell proliferation and enhancing therapeutic outcomes.https://www.mdpi.com/1422-0067/23/20/12666hepatocellular carcinoma (HCC)alpha-fetoprotein (AFP)small interfering RNA (siRNA)angiogenesis inhibitornanoparticle (NP)polylactic-co-glycolic acid (PLGA) |
| spellingShingle | Kittiporn Punuch Chamaiphorn Wongwan Saranrat Jantana Chayapol Somboonyosdech Kamonlatth Rodponthukwaji Natsuda Kunwong Kytai T. Nguyen Vorapan Sirivatanauksorn Yongyut Sirivatanauksorn Chatchawan Srisawat Primana Punnakitikashem Study of siRNA Delivery via Polymeric Nanoparticles in Combination with Angiogenesis Inhibitor for The Treatment of <i>AFP</i>-Related Liver Cancer International Journal of Molecular Sciences hepatocellular carcinoma (HCC) alpha-fetoprotein (AFP) small interfering RNA (siRNA) angiogenesis inhibitor nanoparticle (NP) polylactic-co-glycolic acid (PLGA) |
| title | Study of siRNA Delivery via Polymeric Nanoparticles in Combination with Angiogenesis Inhibitor for The Treatment of <i>AFP</i>-Related Liver Cancer |
| title_full | Study of siRNA Delivery via Polymeric Nanoparticles in Combination with Angiogenesis Inhibitor for The Treatment of <i>AFP</i>-Related Liver Cancer |
| title_fullStr | Study of siRNA Delivery via Polymeric Nanoparticles in Combination with Angiogenesis Inhibitor for The Treatment of <i>AFP</i>-Related Liver Cancer |
| title_full_unstemmed | Study of siRNA Delivery via Polymeric Nanoparticles in Combination with Angiogenesis Inhibitor for The Treatment of <i>AFP</i>-Related Liver Cancer |
| title_short | Study of siRNA Delivery via Polymeric Nanoparticles in Combination with Angiogenesis Inhibitor for The Treatment of <i>AFP</i>-Related Liver Cancer |
| title_sort | study of sirna delivery via polymeric nanoparticles in combination with angiogenesis inhibitor for the treatment of i afp i related liver cancer |
| topic | hepatocellular carcinoma (HCC) alpha-fetoprotein (AFP) small interfering RNA (siRNA) angiogenesis inhibitor nanoparticle (NP) polylactic-co-glycolic acid (PLGA) |
| url | https://www.mdpi.com/1422-0067/23/20/12666 |
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