Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jan;19(1):490-498.
doi: 10.3892/mmr.2018.9689. Epub 2018 Nov 23.

Cabazitaxel liposomes with aptamer modification enhance tumor‑targeting efficacy in nude mice

Affiliations

Cabazitaxel liposomes with aptamer modification enhance tumor‑targeting efficacy in nude mice

Yuzhu Cheng et al. Mol Med Rep. 2019 Jan.

Abstract

The present study investigated the feasibility of improving the tumor‑targeting efficacy and decreasing the toxicity of liposomal cabazitaxel (Cab) with aptamer modification. The process involved preparing aptamer (TLS1c)‑modified liposomes and studying the behavior of the liposomes in vitro and in vivo. TLS1c as an aptamer, which has high specificity for BNL 1ME A.7R.1 (MEAR) cells, was conjugated with Cab liposomes (Cab/lipo) to enhance MEAR tumor tissue targeting. Confocal laser scanning microscopy and flow cytometry analyses demonstrated that the fluorescence of the liposomes modified with the aptamer was notably stronger compared with that of the unmodified liposomes. Furthermore, the biodistribution data of the modified liposomes tested in tumor‑bearing mice revealed high specificity of biotinylated TLS1c‑modified Cab/lipo (BioTL‑Cab/lipo) for tumor tissues. Furthermore, the modified liposomes demonstrated decreased cytotoxicity and simultaneously retained potent inhibition against tumor growth. It is likely that the specific binding of the aptamer (TLS1c) to the targeted cells (MEAR) facilitates the binding of the liposomes to the targeted cells. Therefore, BioTL‑Cab/lipo may be considered as a promising delivery system to improve cell targeting and reduce drug toxicity in the treatment of cancer.

Keywords: aptamers; cabazitaxel; liposomes; tumor-targeting; TLS1c; nude mice.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Flow cytometry analysis of fluorescence intensity of MEAR cells treated with different ratios of BioTL (aptamers) to SPC (0.2, 1 and 2 µg/mg), measured at incubation times of 1, 3 and 5 h (excitation wavelength, 452 nm, emission wavelength, 521 nm). **P<0.01 vs. the ratios of 1 µg/mg BioTL/SPC at 5 h. MEAR, BNL 1ME A.7R.1 cells; BioTL, biotinylated TLS1c; SPC, soya phosphatidyl choline.
Figure 2.
Figure 2.
Effect of Cab solution, Cab/lipo and BioTL-Cab/lipo on the inhibition of MEAR, HepG2 and Caco-2 cell viability. (A) Viability of MEAR cells treated with different concentrations of Cab solution after 24, 48 and 72 h. *P<0.05, **P<0.01 vs. Control. (B) Viability of MEAR, HepG2 and Caco-2 cells treated with Cab solution, Cab/lipo and BioTL-Cab/lipo after 24 h. All values are presented as the mean ± standard deviation. **P<0.01 vs. BioTL-Cab/lipo-treated MEAR cells, Cab/lipo or drug solution. MEAR, BNL 1ME A.7R.1 cells; Cab, cabazitaxel; BioTL, biotinylated TLS1c; lipo, liposomes.
Figure 3.
Figure 3.
Confocal laser scanning microscopy images of DAPI (blue) and 6-FAM (green) of MEAR, Caco-2 or HepG2 cells treated with 6-FAM/Lipo or BioTL-6-FAM/Lipo for 3 h. MEAR, BNL 1ME A.7R.1 cells; BioTL, biotinylated TLS1c; 6-FAM, 6-carboxy fluorescein; lipo, liposomes.
Figure 4.
Figure 4.
Effect of MEAR, Caco-2, HepG2 or macrophage cells on the uptake of 6-FAM/Lipo or BioTL-6-FAM/Lipo. (A) Quantitative flow cytometry analysis of cells following treatment for 3 h. (B) Flow cytometry analysis of fluorescence intensity. All values are presented as the mean ± standard deviation. **P<0.01 vs. 6-FAM-Lipo-treated MEAR cells. MEAR, BNL 1ME A.7R.1 cells; 6-FAM, 6-carboxy fluorescein; FITC, fluorescein isothiocyanate; lipo, liposomes.
Figure 5.
Figure 5.
In vivo real-time images of mice following tail vein injection of liposomes at different times for 24 h. The yellow arrow indicates the location of the tumor. BioTL, biotinylated TLS1c; Cab, cabazitaxel; Dil, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate.
Figure 6.
Figure 6.
Antitumor effect on MEAR-tumor bearing mice treated with liposomes and drug solution compared with the NS group. (A) Tumor volume alters as a function of time following intravenous injection at 48 h after the last injection. **P<0.01 vs. the NS group. (B) Tumor weight of the mice treated at 48 h after the last injection. (C) Standardized body weight of mice treated at 48 h after the last injection. n=6. All values are presented as the mean ± standard deviation. *P<0.05, **P<0.01 vs. the NS group. #P<0.05 vs. the Cab/lipo. Cab/lipo, cabazitaxel liposomes; HBG, high BioTL-Cab/lipo dose group; LBG, low BioTL-Cab/lipo dose group; MBG, middle BioTL-Cab/lipo dose group; MEAR, BNL 1ME A.7R.1; NS, negative control.

Similar articles

Cited by

References

    1. Force T, Kerkela R. Cardiotoxicity of the new cancer therapeutics-mechanisms of, and approaches to, the problem. Drug Discov Today. 2008;13:778–784. doi: 10.1016/j.drudis.2008.05.011. - DOI - PMC - PubMed
    1. Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage t4 DNA polymerase. Science. 1990;249:505–510. doi: 10.1126/science.2200121. - DOI - PubMed
    1. Shangguan D, Li Y, Tang Z, Cao ZC, Chen HW, Mallikaratchy P, Sefah K, Yang CJ, Tan W. Aptamers evolved from live cells as effective molecular probes for cancer study. Proc Natl Acad Sci USA. 2006;103:11838–11843. doi: 10.1073/pnas.0602615103. - DOI - PMC - PubMed
    1. Taghdisi SM, Lavaee P, Ramezani M, Abnous K. Reversible Targeting and controlled release delivery of daunorubicin to cancer cells by aptamer-wrapped carbon nanotubes. Eur J Pharm Biopharm. 2011;77:200–206. doi: 10.1016/j.ejpb.2010.12.005. - DOI - PubMed
    1. Shigdar S, Macdonald J, O'Connor M, Wang T, Xiang D, Al Shamaileh H, Qiao L, Wei M, Zhou SF, Zhu Y, et al. Aptamers as theranostic agents: Modifications, serum stability and functionalisation. Sensors (Basel) 2013;13:13624–13637. doi: 10.3390/s131013624. - DOI - PMC - PubMed

MeSH terms