PMID- 33440348 OWN - NLM STAT- MEDLINE DCOM- 20210510 LR - 20210510 IS - 1945-4589 (Electronic) IS - 1945-4589 (Linking) VI - 13 IP - 2 DP - 2021 Jan 13 TI - Multiwalled carbon nanotubes co-delivering sorafenib and epidermal growth factor receptor siRNA enhanced tumor-suppressing effect on liver cancer. PG - 1872-1882 LID - 10.18632/aging.103905 [doi] AB - OBJECTIVE: This study aimed to investigate the effects of multiwalled carbon nanotubes (MWNTs) co-delivering sorafenib (Sor) and epidermal growth factor receptor (EGFR) siRNA (MWNT/Sor/siRNA) on tumor growth in liver cancer (LC). RESULTS: MWNT/Sor/siRNA was proved to possess increased Sor release, high siRNA stability, and enhanced cellular uptake. In addition, MWNT treatment has few effects on cell proliferation and apoptosis in HepG2 cells; however, MWNT/Sor/siRNA treatment significantly inhibited clone number and induced cell apoptosis, which shows a more favorable antitumor effect than MWNT/Sor and free Sor and free siRNA in HepG2 cells. Moreover MWNT/Sor/siRNA treatment has the most significant antitumor effect in vivo. CONCLUSIONS: MWNT/Sor/siRNA exhibited a superior antitumor effect in vitro and in vivo. METHODS: The MWNT/Sor and MWNT/Sor/siRNA were prepared, and then the morphologies of MWNT/Sor/siRNA were analyzed. In vitro Sor release assay, siRNA stability and cellular uptake of MWNT/Sor/siRNA were performed as well. Next, the effects of MWNT, free Sor, free siRNA, MWNT/Sor and MWNT/Sor/siRNA were evaluated by colony-forming assay, and cell apoptosis assay in HepG2 cells. Meanwhile, the level of EGFR and proteins associated with apoptosis was tested. Furthermore, the anti-tumor effects of MWNT/Sor/siRNA on LC xenograft mice were also unraveled. FAU - Wen, Zhili AU - Wen Z AD - Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Feng, Yuliang AU - Feng Y AD - Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA. FAU - Hu, Youwen AU - Hu Y AD - Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Lian, Lingyan AU - Lian L AD - Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Huang, Hongyan AU - Huang H AD - Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Guo, Li AU - Guo L AD - Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Chen, Shanwen AU - Chen S AD - Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Yang, Qian AU - Yang Q AD - Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Zhang, Moran AU - Zhang M AD - Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Wan, Lijun AU - Wan L AD - Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Xu, Kedong AU - Xu K AD - Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Degejirifu AU - Degejirifu AD - Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China. FAU - Yan, Xiaohua AU - Yan X AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210113 PL - United States TA - Aging (Albany NY) JT - Aging JID - 101508617 RN - 0 (Antineoplastic Agents) RN - 0 (Nanotubes, Carbon) RN - 0 (RNA, Small Interfering) RN - 9ZOQ3TZI87 (Sorafenib) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Animals MH - Antineoplastic Agents/administration & dosage/*therapeutic use MH - Apoptosis/drug effects MH - Cell Proliferation/drug effects MH - *Drug Delivery Systems MH - ErbB Receptors/*genetics/metabolism MH - Hep G2 Cells MH - Humans MH - Liver/drug effects/metabolism MH - Liver Neoplasms/*drug therapy/genetics MH - Mice MH - Mice, Nude MH - *Nanotubes, Carbon MH - Neoplasm Transplantation MH - RNA, Small Interfering/administration & dosage/*therapeutic use MH - Sorafenib/administration & dosage/*therapeutic use PMC - PMC7880368 OTO - NOTNLM OT - epidermal growth factor receptor OT - liver cancer OT - multiwalled carbon nanotubes OT - sorafenib COIS- CONFLICTS OF INTEREST: The author reports no conflicts of interest in this work. EDAT- 2021/01/14 06:00 MHDA- 2021/05/11 06:00 PMCR- 2021/01/31 CRDT- 2021/01/13 20:09 PHST- 2020/05/02 00:00 [received] PHST- 2020/07/21 00:00 [accepted] PHST- 2021/01/14 06:00 [pubmed] PHST- 2021/05/11 06:00 [medline] PHST- 2021/01/13 20:09 [entrez] PHST- 2021/01/31 00:00 [pmc-release] AID - 103905 [pii] AID - 10.18632/aging.103905 [doi] PST - ppublish SO - Aging (Albany NY). 2021 Jan 13;13(2):1872-1882. doi: 10.18632/aging.103905. Epub 2021 Jan 13.