PMID- 30538464 OWN - NLM STAT- MEDLINE DCOM- 20190114 LR - 20220330 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 13 DP - 2018 TI - Targeted delivery of reduced graphene oxide nanosheets using multifunctional ultrasound nanobubbles for visualization and enhanced photothermal therapy. PG - 7859-7872 LID - 10.2147/IJN.S181268 [doi] AB - Ultrasound molecular imaging as a promising strategy, which involved the use of molecularly targeted contrast agents, combined the advantages of contrast-enhanced ultrasound with the photothermal effect of reduced graphene oxide (rGO). METHODS AND RESULTS: The heparin sulfate proteoglycan glypican-3 (GPC3) is a potential molecular target for hepatocellular carcinoma (HCC). In this study, we covalently linked biotinylated GPC3 antibody to PEGylated nano-rGO to obtain GPC3-modified rGO-PEG (rGO-GPC3), and then combined rGO-GPC3 with avidinylated nanobubbles (NBs) using biotin-avidin system to prepare NBs-GPC3-rGO with photothermal effect and dispersibility, solubility in physiological environment. The average size of NBs-GPC3-rGO complex was 700.4+/-52.9 nm due to the polymerization of biotin-avidin system. Scanning electron microscope (SEM) showed NBs-GPC3-rGO attached to human hepatocellular carcinoma HepG2 cell. The ultrasound-targeted nanobubble destruction (UTND) technology make use of the physical energy of ultrasound exposure for the improvement of rGO delivery. Compared with other control groups, the highest nanobubble destruction efficiency of NBs-GPC3-rGO was attributed to the dissection effect of rGO on UTND. This is a positive feedback effect that leads to an increase in the concentration of rGO around the HepG2 cell. So NBs-GPC3-rGO using UTND and near-infrared (NIR) irradiation resulted in cell viability within 24 h, 48 h, 72 h lower than other treatment groups. CONCLUSION: This work established NBs-GPC3-rGO as an ultrasonic photothermal agent due to its suitable size, imaging capability, photothermal efficiency for visual photothermal therapy in vitro. FAU - Liu, Zhao AU - Liu Z AD - Department of Ultrasound, Harbin Medical University Cancer Hospital, Nangang District, Harbin 150080, China, chengwen69@yahoo.com. FAU - Zhang, Jia AU - Zhang J AD - Key Laboratory of Microsystems and Microstructure Manufacturing, Ministry of Education, Harbin Institute of Technology, Harbin 150080, China. FAU - Tian, Yuhang AU - Tian Y AD - Department of Ultrasound, Harbin Medical University Cancer Hospital, Nangang District, Harbin 150080, China, chengwen69@yahoo.com. FAU - Zhang, Lei AU - Zhang L AD - Department of Ultrasound, Harbin Medical University Cancer Hospital, Nangang District, Harbin 150080, China, chengwen69@yahoo.com. FAU - Han, Xue AU - Han X AD - Department of Ultrasound, Harbin Medical University Cancer Hospital, Nangang District, Harbin 150080, China, chengwen69@yahoo.com. FAU - Wang, Qiucheng AU - Wang Q AD - Department of Ultrasound, Harbin Medical University Cancer Hospital, Nangang District, Harbin 150080, China, chengwen69@yahoo.com. FAU - Cheng, Wen AU - Cheng W AD - Department of Ultrasound, Harbin Medical University Cancer Hospital, Nangang District, Harbin 150080, China, chengwen69@yahoo.com. LA - eng PT - Journal Article DEP - 20181122 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 RN - 0 (Glypicans) RN - 0 (graphene oxide) RN - 7782-42-5 (Graphite) SB - IM EIN - Int J Nanomedicine. 2019 Apr 08;14:2449-2450. PMID: 31040667 MH - Cell Survival MH - Glypicans/metabolism MH - Graphite/*chemistry MH - Hep G2 Cells MH - Humans MH - Hyperthermia, Induced/*methods MH - *Microbubbles MH - Nanoparticles/*chemistry/ultrastructure MH - Oxidation-Reduction MH - Phototherapy/*methods MH - *Ultrasonics PMC - PMC6255282 OTO - NOTNLM OT - HepG2 cell OT - glypican-3 OT - photothermal therapy OT - reduced graphene oxide OT - ultrasound-targeted nanobubble destruction COIS- Disclosure The authors report no conflicts of interest in this work. EDAT- 2018/12/13 06:00 MHDA- 2019/01/15 06:00 PMCR- 2018/11/22 CRDT- 2018/12/13 06:00 PHST- 2018/12/13 06:00 [entrez] PHST- 2018/12/13 06:00 [pubmed] PHST- 2019/01/15 06:00 [medline] PHST- 2018/11/22 00:00 [pmc-release] AID - ijn-13-7859 [pii] AID - 10.2147/IJN.S181268 [doi] PST - epublish SO - Int J Nanomedicine. 2018 Nov 22;13:7859-7872. doi: 10.2147/IJN.S181268. eCollection 2018.