Study of the efficiency of cellular accumulation of doxorubicin supplied with a targeted delivery system based on phospholipid nanoparticles with integrin-directed peptide
Chemotherapeutic agents containing targeted systems are a promising pathway to increase the effectiveness of glioblastoma treatment. Specific proteins characterized by increased expression on the surface of tumor cells are considered as possible targets. Integrin αvβ3 is one of such proteins on the cell surface. It effectively binds the cyclic Arg-Gly-Asp (cRGD) peptide. In this study, the cRGD peptide-modified doxorubicin (Dox) phospholipid composition was investigated. The particle size of this composition was 43.76±2.09 nm, the ζ-potential was 4.33±0.54 mV. Dox was almost completely incorporated into the nanoparticles (99.7±0.58%). The drug release increased in an acidic medium (at pH 5.0 of about 35±3.2%). The total accumulation and internalization of Dox used the composition of phospholipid nanoparticles with the targeted vector was 1.4-fold higher as compared to the free form. In the HeLa cell line (not expressing αvβ3 integrin) this effect was not observed. These results suggest the prospects of using the cyclic RGD peptide in the delivery of Dox to glioblastoma cells and the feasibility of further investigation of the mechanism of action of the entire composition as a whole.
Kostryukova L.V., Tereshkina Yu.A., Tikhonova E.G., Sanzhakov M.A., Bobrova D.V., Khudoklinova Yu.Yu. (2022) Study of the efficiency of cellular accumulation of doxorubicin supplied with a targeted delivery system based on phospholipid nanoparticles with integrin-directed peptide. Biomeditsinskaya Khimiya, 68(6), 437-443.
Kostryukova L.V. et al. Study of the efficiency of cellular accumulation of doxorubicin supplied with a targeted delivery system based on phospholipid nanoparticles with integrin-directed peptide // Biomeditsinskaya Khimiya. - 2022. - V. 68. -N 6. - P. 437-443.
Kostryukova L.V. et al., "Study of the efficiency of cellular accumulation of doxorubicin supplied with a targeted delivery system based on phospholipid nanoparticles with integrin-directed peptide." Biomeditsinskaya Khimiya 68.6 (2022): 437-443.
Kostryukova, L. V., Tereshkina, Yu. A., Tikhonova, E. G., Sanzhakov, M. A., Bobrova, D. V., Khudoklinova, Yu. Yu. (2022). Study of the efficiency of cellular accumulation of doxorubicin supplied with a targeted delivery system based on phospholipid nanoparticles with integrin-directed peptide. Biomeditsinskaya Khimiya, 68(6), 437-443.
References
Luo C., Song K., Wu S., Hameed N.F., Kudulaiti N., Xu H., Qin Z.Y., Wu J.S. (2021) The prognosis of glioblastoma: A large, multifactorial study. Br. J. Neurosurg., 35(5), 555-561. CrossRef Scholar google search
Zhang C., Song J., Lou L., Qi X., Zhao L., Fan B., Sun G., Lv Z., Fan Z., Jiao B., Yang J. (2021) Doxorubicin-loaded nanoparticle coated with endothelial cells-derived exosomes for immunogenic chemotherapy of glioblastoma. Bioeng. Transl. Med, 6(3), e10203. CrossRef Scholar google search
Touat M., Idbaih A., Sanson M., Ligon K.L. (2017) Glioblastoma targeted therapy: Updated approaches from recent biological insights. Annals Oncology, 28(7), 1457-1472. CrossRef Scholar google search
Cheng T.M., Chang W.J., Chu H.Y., de Luca R., Pedersen J.Z., Incerpi S., Li Z., Shih Y., Lin H., Wang K., Whang-Peng J. (2021) Nano-strategies targeting the integrin αvβ3 network for cancer therapy. Cells, 10(7), 1684. CrossRef Scholar google search
Desgrosellier J.S., Cheresh D.A. (2010) Integrins in cancer: Biological implications and therapeutic opportunities. Nature Reviews Cancer, 10(1), 9-22. CrossRef Scholar google search
Hood J.D., Cheresh D.A. (2002) Role of integrins in cell invasion and migration. Nature Reviews Cancer, 2, 958-959. CrossRef Scholar google search
Bello L., Francolini M., Marthyn P., Zhang J., Carroll R.S., Nikas D.C., Strasser J.F., Villani R., Cheresh D.A., Black P.M. (2001) Alpha(v)beta3 and alpha(v)beta5 integrin expression in glioma periphery. Neurosurgery-Hagerstown, 49(2), 380-390. CrossRef Scholar google search
Echavidre W., Picco V., Faraggi M., Montemagno C. (2022) Integrin-αvβ3 as a therapeutic target in glioblastoma: Back to the future? Pharmaceutics, 14(5), 1053. CrossRef Scholar google search
Wei X., Chen X., Ying M., Lu W. (2014) Brain tumor-targeted drug delivery strategies. Acta Pharmaceutica Sinica B, 4(3), 193-201. CrossRef Scholar google search
Liolios C., Sachpekidis C., Kolocouris A., Dimitrakopoulou-Strauss A., Bouziotis P. (2021) PET diagnostic molecules utilizing multimeric cyclic RGD peptide analogs for imaging integrin αvβ3 receptors. Molecules, 26(6), 1792. CrossRef Scholar google search
Gečys D., Kazlauskas A., Gečytė E., Paužienė N., Kulakauskienė D., Lukminaitė I., Jekabsone A. (2022) Internalisation of RGD-engineered extracellular vesicles by glioblastoma cells. Biology, 11(10), 1483. CrossRef Scholar google search
Zhan C., Meng Q., Li Q., Feng L., Zhu J., Lu W. (2012) Cyclic RGD-polyethylene glycol-polyethylenimine for intracranial glioblastoma-targeted gene delivery. Chemistry – An Asian Journal, 7(1), 91-96. CrossRef Scholar google search
Garanti T., Alhnan M.A., Wan K.W. (2020) RGD-decorated solid lipid nanoparticles enhance tumor targeting, penetration and anticancer effect of asiatic acid. Nanomedicine, 15(16), 1567-1583. CrossRef Scholar google search
Wang F., Li Y., Shen Y., Wang A., Wang S., Xie T. (2013) The functions and applications of RGD in tumor therapy and tissue engineering. Int. J. Mol. Sci., 14(7), 13447-13462. CrossRef Scholar google search
Liu C., Zhao W., Zhang L., Sun H., Chen X., Deng N. (2022) Preparation of DSPE-PEG-cRGD modified cationic liposomes for delivery of OC-2 shRNA and the antitumor effects on breast cancer. Pharmaceutics, 14(10), 2157. CrossRef Scholar google search
Li L., He D., Guo Q., Zhang Z., Ru D., Wang L., Gong K., Liu F., Duan Y., Li H. (2022) Exosome-liposome hybrid nanoparticle codelivery of TP and miR497 conspicuously overcomes chemoresistant ovarian cancer. J. Nanobiotechnology, 20(1), 1-22. CrossRef Scholar google search
Torchilin V.P. (2005). Recent advances with liposomes as pharmaceutical carriers. Nature Rev. Drug Discov., 4(2), 145-160. CrossRef Scholar google search
Zhang Y., Xi K., Fu X., Sun H., Wang H., Yu D., Li Z., Ma Y., Liu X., Huang B., Wang J., Li G., Cui J., Li X., Ni S. (2021) Versatile metal-phenolic network nanoparticles for multitargeted combination therapy and magnetic resonance tracing in glioblastoma. Biomaterials, 278, 121163. CrossRef Scholar google search
Kasenda B., König D., Manni M., Ritschard R., Duthaler U., Bartoszek E., Bärenwaldt A., Deuster S., Hutter G., Cordier D., Mariani L., Hench J., Frank S., Krähenbühl S., Zippelius A., Rochlitz C., Mamot C., Wicki A., Läubli H. (2022) Targeting immunoliposomes to EGFR-positive glioblastoma. ESMO Open, 7(1), 100365. CrossRef Scholar google search
Chen J., Dai Q., Yang Q., Bao X., Zhou Y., Zhong H., Wu L., Wang T., Zhang Z., Lu Y., Zhang Z., Lin M., Han M., Wei Q. (2022) Therapeutic nucleus-access BNCT drug combined CD47-targeting gene editing in glioblastoma. J. Nanobiotechnology, 20(1), 1-18. CrossRef Scholar google search
He C., Zhang Z., Ding Y., Xue K., Wang X., Yang R., An Y., Liu D., Hu C., Tang Q. (2021) LRP1-mediated pH-sensitive polymersomes facilitate combination therapy of glioblastoma in vitro and in vivo. J. Nanobiotechnology, 19(1), 1-17. CrossRef Scholar google search
Medvedeva N.V., Torkhovskaya T.I., Kostryukova L.V., Zakharova T.S., Kudinov V.A., Kasatkina E.O., Prozorovskiy V.N., Ipatova O.M. (2017) Influence of doxorubicin inclusion into phospholipid nanoparticles on tumor accumulation and specific activity. Biomeditsinskaya Khimiya, 63(1), 56-61. CrossRef Scholar google search
Nemtsova E.R., Tikhonova E.G., Bezborodova O.A., Pankratov A.A., Venediktova J.B., Korotkevich E.I., Kostryukova L.V., Tereshkina J.A. (2020) Preclinical study of pharmacological properties of doxorubicin-NPh. Bull. Exper. Biol. Med., 169(6), 778-782. CrossRef Scholar google search
Kostryukova L.V., Tereshkina Y.A., Korotkevich E.I., Prozorovsky V.N., Torkhovskaya T.I., Morozevich G.E., Toropygin I.Y., Konstantinov M.A., Tikhonova E.G. (2020) Targeted drug delivery system for doxorubicin based on a specific peptide and phospholipid nanoparticles. Biomeditsinskaya Khimiya, 66(6), 464-468. CrossRef Scholar google search
Prozorovskiy V.N., Kostryukova L.V., Korotkevich E.I., Torkhovskaya T.I., Morozevich G.E., Tikhonova E.G., Ipatova O.M. (2018) Photosensitizer chlorin e6 internalization into tumor cells in phospholipid nanoparticles conjugated with peptide containing the NGR sequence. Biomedical Chemistry: Research and Methods, 1(4), e00063. CrossRef Scholar google search
Tikhonova E.G., Sanzhakov M.A., Tereshkina Y.A., Kostryukova L.V., Khudoklinova Y.Y., Orlova N.A., Bobrova D.V., Ipatova O.M. (2022) Drug transport system based on phospholipid nanoparticles: Production technology and characteristics. Pharmaceutics, 14(11), 2522. CrossRef Scholar google search
Zykova M.A., Ipatova O.M., Prozorovskii V.N., Medvedeva N.V., Voskresenskaya A.A., Zakharova T.S., Torkhovskaya T.I. (2011) Changes in the distribution of doxorubicin in blood and plasma when it is included in the phospholipid nanocomposition. Biomeditsinskaya Khimiya, 57(2), 174-179. CrossRef Scholar google search
Sheldon K., Liu D., Ferguson J., Gariepy J. (1995) Loligomers: Design of de novo peptide-based intracellular vehicles. Proc. Nat. Acad. Sci. USA, 92(6), 2056-2060. CrossRef Scholar google search
He S., Cen B., Liao L., Wang Z., Qin Y., Wu Z., Liao W., Zhang Z., Ji A. (2017) A tumor-targeting cRGD-EGFR siRNA conjugate and its anti-tumor effect on glioblastoma in vitro and in vivo. Drug Delivery, 24(1), 471-481. CrossRef Scholar google search
Li N., Qiu S., Fang Y., Wu J., Li Q. (2021) Comparison of linear vs. cyclic RGD pentapeptide interactions with integrin αvβ3 by molecular dynamics simulations. Biology, 10(7), 688. CrossRef Scholar google search
Xinming L., Tsibouklis J., Weng T., Zhang B., Yin G., Feng G., Cui Y., Savina I., Mikhalovska L., Sandeman S., Howell C., Mikhalovsky S. (2016) Nano carriers for drug transport across the blood-brain barrier. J. Drug Targeting, 25(1), 17-28. CrossRef Scholar google search
Seo J.W., Ang J., Mahakian L.M., Tam S., Fite B., Ingham E.S., Beyer J., Forsayeth J., Bankiewicz K.S., Xu T., Ferrara K.W. (2015) Self-assembled 20-nm 64Cu-micelles enhance accumulation in rat glioblastoma. J. Controlled Release, 220, 51-60. CrossRef Scholar google search
Zhang L., Fan J., Li G., Yin Z., Fu B.M. (2020) Transcellular model for neutral and charged nanoparticles across an in vitro blood-brain barrier. Cardiovasc. Eng. Technol., 11(6), 607-620. CrossRef Scholar google search
Meng F., Zhong Y., Cheng R., Deng C., Zhong Z. (2014) pH-sensitive polymeric nanoparticles for tumor-targeting doxorubicin delivery: Concept and recent advances. Nanomedicine, 9(3), 487-499. CrossRef Scholar google search
Lanzardo S., Conti L., Brioschi C., Bartolomeo M.P., Arosio D., Belvisi L., Manzoni L., Maiocchi A., Maisano F., Forni G. (2011) A new optical imaging probe targeting αvβ3 integrin in glioblastoma xenografts. Contrast Media Molecular Imaging, 6(6), 449-458. CrossRef Scholar google search