Anti-GPC3 antibody-modified sorafenib-loaded nanoparticles significantly inhibited HepG2 hepatocellular carcinoma
Open accessAbstract
Sorafenib (SFB) has improved the treatment of hepatocellular carcinoma (HCC) and has fewer severe side effects than other agents used for that purpose. However, due to a lack of tumor-specific targeting, the concentration of the drug in tumor tissue cannot be permanently maintained at a level that inhibits tumor growth. To overcome this problem, we developed a novel SFB-loaded polymer nanoparticle (NP). The NP (a TPGS-b-PCL copolymer that was synthesized from ε-caprolactone and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) via ring-opening polymerization) contains Pluronic P123 and SFB, and its surface is modified with anti-GPC3 antibody to produce the polymer nanoparticle (NP-SFB-Ab). The Ab-conjugated NPs had higher cellular uptake by HepG2 cells than did non-antibody-conjugated SPD-containing nanoparticles (NP-SFB). The NP-SFB-Ab also displayed better stability characteristics, released higher levels of SFB into cell culture medium, and was more cytotoxic to tumor cells than was non-targeted NP-SFB and free SFB. The NP-SFB-Ab downregulated expression of the anti-apoptosis molecule MCL-1, which led to polymerization of Bax and Bak in mitochondrial cytosol. The NP-SFB-AB also promoted the mitochondrial release of cytochrome C, resulting in cellular apoptosis. Moreover, the NP-SFB-Ab significantly inhibited the growth of HepG2 xenograft tumors in nude mice without producing obvious side effects. These findings suggest that NP-SFB-Ab is a promising new method for achieving targeted therapy of HCC.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The GPC3 molecule on the surface of HepG2 cells can mediate the endocytosis of NPs, so that the cells can more effectively enrich mAb-modified NPs and exert a higher tumor suppressor effect.
“The GPC3 molecule on the surface of HepG2 cells can mediate the endocytosis of NPs, so that the cells can more effectively enrich mAb-modified NPs and exert a higher tumor suppressor effect.212”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [212]
EpCAM is a highly expressed marker in cancer, especially in circulating tumor cells (CTC), and is closely related to poor prognosis.
“EpCAM is a highly expressed marker in cancer, especially in circulating tumor cells (CTC), and is closely related to poor prognosis.212”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [212]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
New knowledge of the mechanisms of sorafenib resistance in liver cancer
Zhu, Y., Zheng, B. J., Wang, H., & Chen, L. (2017) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.5 · Cited by 704 · see citing works
Self-citationZhu, Z.-W., Friess, H., Wang, L., Abou-Shady, M., Zimmermann, A., Lander, A. D., Korc, M., Kleeff, J. H., & Büchler, M. W. (2001) · Gut · doi:10.1136/gut.48.4.558 · Cited by 291 · see citing works
Targeting the differential addiction to anti-apoptotic BCL-2 family for cancer therapy
Inoue‐Yamauchi, A., Jeng, P., Kim, K., Chen, H., Han, S., Ganesan, Y. T., Ishizawa, K., Jebiwott, S., Dong, Y., Pietanza, M. C., et al. (2017) · Nature Communications · doi:10.1038/ncomms16078 · Cited by 176 · see citing works
Gao, W., Tang, Z., Zhang, Y., et al. (2015) · Nature Communications · doi:10.1038/ncomms7536 · Cited by 156 · see citing works
Self-citationMei, L., Zhang, Y., Zheng, Y., Tian, G., Song, C. X., Yang, D., Chen, H., Sun, H., Tian, Y., Liu, K., et al. (2009) · Nanoscale Research Letters · doi:10.1007/s11671-009-9431-6 · Cited by 131 · see citing works
Self-citationLin, T.-T., Gao, D.-Y., Liu, Y.-C., Sung, Y., Wan, D., Liu, J., Chiang, T., Wang, L., & Chen, Y. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.11.003 · Cited by 113 · see citing works
Dargel, C., Bassani‐Sternberg, M., Hasreiter, J., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.05.055 · Cited by 96 · see citing works
Survival and cost‐effectiveness of sorafenib therapy in advanced hepatocellular carcinoma
Parikh, N. D., Marshall, V. D., Singal, A. G., Nathan, H., Lok, A. S.-F., Balkrishnan, R., & Shahinian, V. B. (2016) · Hepatology · doi:10.1002/hep.28881 · Cited by 92 · see citing works
Li, H., Li, Y., Wang, X., Hou, Y., Hong, X., Gong, T., Zhang, Z., & Sun, X. (2017) · Theranostics · doi:10.7150/thno.20745 · Cited by 82 · see citing works
Lin, Q., Yang, Y., Hu, Q., Guo, Z., Liu, T., Xu, J., Wu, J., Kirk, T. B., Ma, D., & Xue, W. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.11.062 · Cited by 80 · see citing works
Self-citationKim, M., Saunders, A. M., Hamaoka, B. Y., Beachy, P. A., & Leahy, D. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1109877108 · Cited by 78 · see citing works
Sharma, S., Verma, A., Pandey, G., Mittapelly, N., & Mishra, P. R. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2015.08.005 · Cited by 77 · see citing works
Redox-triggered activation of nanocarriers for mitochondria-targeting cancer chemotherapy
Zhou, W., Yu, H. M., Zhang, L.-J., Wu, B., Wang, C., Wang, Q., Deng, K., Zhuo, R., & Huang, S. (2017) · Nanoscale · doi:10.1039/c7nr06130g · Cited by 77 · see citing works
Tang, J., Ji, H., Ren, J., Li, M., Zheng, N., & Wu, L. (2016) · Oncology Letters · doi:10.3892/ol.2016.5421 · Cited by 74 · see citing works
Sivalingam, K. S., Poornima, P., Weng, C., et al. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25937 · Cited by 66 · see citing works
Brasacchio, D., Alsop, A. E., Noori, T., Lufti, M., Iyer, S., Simpson, K. J., Bird, P. I., Kluck, R. M., Johnstone, R. W., & Trapani, J. A. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2016.119 · Cited by 63 · see citing works
CD52 inhibits Toll-like receptor activation of NF-κB and triggers apoptosis to suppress inflammation
Rashidi, M., Bandala‐Sanchez, E., Lawlor, K. E., Zhang, Y., Neale, A. M., Vijayaraj, S. L., O’Donoghue, R. J. J., Wentworth, J. M., Adams, T. E., Vince, J. E., et al. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.173 · Cited by 61 · see citing works
Self-citationPinter, M., Weinmann, A., Wörns, M., Hucke, F., Bota, S. I., Marquardt, J. U., Duda, D. G., Jain, R. K., Galle, P. R., Trauner, M. A., et al. (2017) · United European Gastroenterology Journal · doi:10.1177/2050640617695698 · Cited by 55 · see citing works
Presti, G., Guarrasi, V., Gulotta, E., et al. (2017) · Biophysical Chemistry · doi:10.1016/j.bpc.2017.09.002 · Cited by 54 · see citing works
pH responsive cylindrical MSN for oral delivery of insulin-design, fabrication and evaluation
Guha, A., Biswas, N., Bhattacharjee, K., Sahoo, N., & Kuotsu, K. (2016) · Drug Delivery · doi:10.1080/10717544.2016.1209796 · Cited by 53 · see citing works
Avanesov, A. S., Honeyager, S. M., Malicki, J. J., & Blair, S. S. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002503 · Cited by 45 · see citing works
Liu, G., Gao, H., Zuo, Y., Zeng, X., Tao, W., Tsai, H., & Mei, L. (2016) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.6b11917 · Cited by 44 · see citing works
Liu, F., Sun, L., Tang, X., Zhu, H., Cai, S., Zhang, R., & Wei, H. (2014) · International Journal of Nanomedicine · doi:10.2147/ijn.s71623 · Cited by 40 · see citing works
Self-citationWon, J., Yu, S. J., Hwang, C. Y., Cho, S., Park, S., Kim, K., Choi, W., Cho, H., Cho, E. J., Lee, J., et al. (2017) · Hepatology · doi:10.1002/hep.29237 · Cited by 40 · see citing works
Parikh, A. R., Kathawala, K., Tan, C. C., Garg, S., & Zhou, X. (2017) · Drug Delivery · doi:10.1080/10717544.2017.1337825 · Cited by 35 · see citing works
Ansari, S. A., Pendurthi, U. R., & Rao, L. V. M. (2017) · Blood Advances · doi:10.1182/bloodadvances.2017010132 · Cited by 35 · see citing works
PCL-HA microscaffolds for in vitro modular bone tissue engineering
Totaro, A., Salerno, A., Imparato, G., Domingo, C., Urciuolo, F., & Netti, P. A. (2015) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2084 · Cited by 28 · see citing works
Nanoengineering of aggregation-free and thermally-stable gold nanoparticles in mesoporous frameworks
Liu, B., Jiang, T., Zheng, H., Dissanayke, S., Song, W., Federico, A. N., Suib, S. L., & He, J. (2017) · Nanoscale · doi:10.1039/c7nr01988b · Cited by 27 · see citing works
Rapid fabrication of functionalised poly(dimethylsiloxane) microwells for cell aggregate formation
Forget, A., Burzava, A. L. S., Delalat, B., Vasilev, K. A., Harding, F. J., Blencowe, A., & Voelcker, N. H. (2017) · Biomaterials Science · doi:10.1039/c6bm00916f · Cited by 25 · see citing works
Lian, H., He, Z., & Meng, Z. (2017) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2017.04.045 · Cited by 22 · see citing works
Martínez‐Torres, A. C., Reyes‐Ruiz, A., Londoña, M. B., Franco-Molina, M. Á., & Rodrı́guez-Padilla, C. (2018) · BMC Cancer · doi:10.1186/s12885-017-3954-5 · Cited by 22 · see citing works
Zaker, A., Asili, J., Abrishamchi, P., et al. (2017) · PubMed · doi:10.22038/ijbms.2017.9568 · Cited by 17 · see citing works
Hsieh, C.-H., Wang, J.-P., Chiu, C., et al. (2017) · APOPTOSIS · doi:10.1007/s10495-017-1432-9 · Cited by 15 · see citing works
Nakamura, I., Iimuro, Y., Hai, S., et al. (2018) · European Surgical Research · doi:10.1159/000484044 · Cited by 14 · see citing works
Li, M., Wang, W., Dan, Y., Tong, Z., Chen, W., Qin, L., Liu, K., Li, W., Mo, P., & Yu, C. (2016) · Oncotarget · doi:10.18632/oncotarget.8812 · Cited by 11 · see citing works
Progress towards molecular patient stratification of hepatocellular carcinoma: Lost in translation?
Chiang, D. Y., & Villanueva, A. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.07.031 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Smart nanoparticles for cancer therapy
Sun, L., Liu, H., Ye, Y., Lei, Y., Islam, R., Tan, S., Tong, R., Miao, Y.-B., & Cai, L. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01642-x · Cited by 1,073 · see citing works
- Authors
- Tang, X., Chen, L., Li, A., Cai, S., Zhang, Y., Liu, X., Jiang, Z., Liu, X., Liang, Y., & Ma, D.
- Affiliations
- Anhui University of Science and Technology (CN)
- Yangzhou University (CN)
- Jinan University (CN)
- Xuzhou Medical College (CN)
- Corresponding author
- Liang, Yong
- Ma, Dong
- Venue
- Drug Delivery
- Publisher
- Informa UK Limited
- Published
- 2018-01-01
- Volume
- 25
- Issue
- 1
- Pages
- 1484-1494
- ISSN
- 1071-7544 (ISSN-L)
- 1521-0464
- PMC
- PMC6058710
- OpenAlex
- W2809179038
- Cited by
- 64
- References
- 36
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 2 · 2023: 8 · 2022: 5 · 2021: 17 · 2020: 11 · 2019: 9 · 2018: 2 · 2017: 1
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Drug Delivery (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Figshare (cc-by)
- Funders
- National Natural Science Fund of China (81572431, 81773281)
- Anhui Provincial Science and Technology Program (1604a0802094, KJ2018ZD011)
- Huainan Science and Technology Project (2017B41, QNRC2016421, WSN-252, HAA201740)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- sorafenib, hepatocellular carcinoma, HepG2 cells, antibody-conjugated nanoparticles, Pluronic P123, targeted drug delivery, apoptosis, Mcl-1, cytochrome c release, mitochondrial apoptosis, nanoparticle drug release, tumor xenografts
- MeSH terms
- Sorafenib, Animals, Antibodies, Antineoplastic Agents, Caproates, Carcinoma, Hepatocellular, Humans, Lactones, Liver Neoplasms, Mice, Inbred BALB C, Mice, Nude, Niacinamide, Phenylurea Compounds, Polyethylene Glycols, Polymers, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice, Glypicans, Nanoparticles, Hep G2 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
