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
. 2020 Dec 31:15:10547-10559.
doi: 10.2147/IJN.S276336. eCollection 2020.

Tuftsin-Bearing Liposomes Co-Encapsulated with Doxorubicin and Curcumin Efficiently Inhibit EAC Tumor Growth in Mice

Kalaimathi Murugesan  1 , Padmapriya Srinivasan #  1 , Raghunandan Mahadeva #  1 , Chhitar M Gupta  1 , Wahajul Haq  2
Affiliations

Tuftsin-Bearing Liposomes Co-Encapsulated with Doxorubicin and Curcumin Efficiently Inhibit EAC Tumor Growth in Mice

Kalaimathi Murugesan et al. Int J Nanomedicine. .

Abstract

Background: Targeted multidrug-loaded delivery systems have emerged as an advanced strategy for cancer treatment. In this context, antibodies, hormones, and small peptides have been coupled to the surface of drug carriers, such as liposomes, polymeric and metallic nanoparticles loaded with drugs, as tumor-specific ligands. In the present study, we have grafted a natural macrophage stimulating peptide, tuftsin, on the surface of the liposomes (LPs) that were loaded with doxorubicin (DOX) and/or curcumin (CUR), by attaching to its C-terminus a palmitoyl residue (Thr-Lys-Pro-Arg-CO-NH-(CH2)2-NH-COC15H31, P.Tuft) to enable its grafting within the liposome's bilayer.

Methods: The prepared drug-loaded liposomes (DOX LPs, CUR LPs, DOX-CUR LPs, P.Tuft-LPs, P.Tuft-DOX LPs, P.Tuft-CUR LPs, P.Tuft-DOX-CUR LPs) were thoroughly characterised in terms of particle size, drug content, encapsulation efficiency and structural properties using UV-visible spectroscopy, dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR). The anti-cancer activity and drug toxicity of the liposomal formulations were examined on Ehrlich ascites carcinoma (EAC) tumor-induced mice model.

Results: A significant reduction in the tumor weight and volume was observed upon treating the tumor-bearing mice with palmitoyl tuftsin-grafted dual drug-loaded liposomes (P.Tuft-DOX-CUR LPs), as compared to the single drug/peptide-loaded formulation (DOX LPs, CUR LPs, DOX-CUR LPs, P.Tuft- LPs, P.Tuft-DOX LPs, P.Tuft-CUR LPs). Western blot analysis revealed that the tumor inhibition was associated with p53-mediated apoptotic pathway. Further, the biochemical and histological analysis revealed that the various liposomal preparation used in this study were non-toxic to the animals at the specified dose (10mg/kg).

Conclusion: In conclusion, we have developed a targeted liposomal formulation of P.Tuftsin-bearing liposomes co-encapsulated with effective anti-cancer drugs such as doxorubicin and curcumin. In experimental animals, tumor inhibition by P.Tuft-DOX-CUR LPs indicates the synergistic therapeutic effect of the peptide and the dual drug.

Keywords: antitumor; curcumin; doxorubicin; palmitoyl-tuftsin.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest for this work.

Figures

Figure 1
Figure 1
The schematic representation of the assembly of tuftsin-bearing liposomes encapsulated with DOX and CUR.
Figure 2
Figure 2
Size determination of LPs.
Figure 3
Figure 3
Characterisation of LPs.
Figure 4
Figure 4
Characterization of structural properties by Fourier transform infrared spectroscopy (FTIR).
Figure 5
Figure 5
In vitro release profile of DOX and CUR.
Figure 6
Figure 6
In vitro cellular uptake study.
Figure 7
Figure 7
The in vivo effects different kinds of LPs in EAC tumor-bearing mice.
Figure 8
Figure 8
Apoptosis protein expression in tumor tissues.
Figure 9
Figure 9
Schematic representation of p53-mediated apoptotic pathway.
Figure 10
Figure 10
Assessment of liver toxicity in mice on treatment with different kinds of LPs.
Figure 11
Figure 11
The micrographs of H&E-stained sections of the main organs and tumors after treatment with different kinds of LPs.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Glasgow MDK, Chougule. MB. Recent developments in active tumor targeted multifunctional nanoparticles for combination chemotherapy in cancer treatment and imaging. J Biomed Nanotechnol. 2015;11(11):1859–1898. doi:10.1166/jbn.2015.2145 - DOI - PMC - PubMed
    1. Pastorino F, Brignole C, Paolo DD, et al. Targeting liposomal chemotherapy via both tumor cell-specific and tumor vasculature-specific ligands potentiates therapeutic efficacy. Cancer Res. 2006;66(20):10073–10082. doi:10.1158/0008-5472.CAN-06-2117 - DOI - PubMed
    1. Barui S, Saha S, Mondal G, Haseena S, Chaudhuri A. Simultaneous Delivery of doxorubicin and curcumin encapsulated in liposomes of pegylated RGDK-lipopeptide to tumor vasculature. Biomaterials. 2014;35(5):1643–1656. doi:10.1016/j.biomaterials.2013.10.074 - DOI - PubMed
    1. Sengupta S, Eavarone D, Capila I, et al. Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system. Nature. 2005;436(7050):568–572. doi:10.1038/nature03794 - DOI - PubMed
    1. Agarwal A, Kandpal H, Gupta HP, Singh NB, Gupta CM. Tuftsin-bearing liposomes as rifampin vehicles in treatment of tuberculosis in mice. Antimicrob Agents Chemother. 1994;38(3):588–593. - PMC - PubMed

MeSH terms