Dual-functionalized Liposomal Delivery System for Solid Tumors Based on RGD and a PH-responsive Antimicrobial Peptide

Overview

Journal Sci Rep

Specialty Science

Date 2016 Feb 5

PMID 26842655

Citations 20

Authors

Qianyu Zhang

Libao Lu

Li Zhang

Kairong Shi

Xingli Cun

Yuting Yang

Yayuan Liu

Huile Gao

Qin He

Affiliations

Soon will be listed here.

Abstract

[D]-H6L9, as a pH-responsive anti-microbial peptide (AMP), has been evidenced by us to be an excellent choice in tumor microenvironment-responsive delivery as it could render liposomes responsive to the acidified tumor microenvironment. However, [D]-H6L9-modified liposomes could not actively target to tumor area. Therefore, integrin αvβ3-targeted peptide RGD was co-modified with [D]-H6L9 onto liposomes [(R + D)-Lip] for improved tumor delivery efficiency. Under pH 6.3, (R + D)-Lip could be taken up by C26 cells and C26 tumor spheroids (integrin αvβ3-positive) with significantly improved efficiency compared with other groups, which was contributed by both RGD and [D]-H6L9, while RGD did not increase the cellular uptake performance on MCF-7 cells (integrin αvβ3-negative). Results showed that RGD could decrease cellular uptake of (R + D)-Lip while [D]-H6L9 could increase it, implying the role of both RGD and [D]-H6L9 in cellular internalization of (R + D)-Lip. On the other hand, (R + D)-Lip could escape the entrapment of lysosomes. PTX-loaded (R + D)-Lip could further increase the cellular toxicity against C26 cells compared with liposomes modified only with RGD and [D]-H6L9 respectively, and achieve remarkable tumor inhibition effect on C26 tumor models.

Citing Articles

Nanocodelivery of 5-Fluorouracil and Curcumin by RGD-Decorated Nanoliposomes Achieves Synergistic Chemotherapy for Breast Cancer.

Mahmoudi R, Mohammadi S, Mahmoudi R, Fouani M, Ardakani M, Hadi A IET Nanobiotechnol. 2024; 2024:4959295.

PMID: 39629226 PMC: 11614510. DOI: 10.1049/nbt2/4959295.

Lipid-Based Nanotechnology: Liposome.

Jiang Y, Li W, Wang Z, Lu J Pharmaceutics. 2024; 16(1).

PMID: 38258045 PMC: 10820119. DOI: 10.3390/pharmaceutics16010034.

Antiviral polysaccharide and antiviral peptide delivering nanomaterials for prevention and treatment of SARS-CoV-2 caused COVID-19 and other viral diseases.

Homaeigohar S, Liu X, Elbahri M J Control Release. 2023; 358:476-497.

PMID: 37164241 PMC: 10182878. DOI: 10.1016/j.jconrel.2023.05.010.

Drug Release from Nanoparticles (Polymeric Nanocapsules and Liposomes) Mimed through a Multifractal Tunnelling-Type Effect.

Bacaita E, Rata D, Cadinoiu A, Ghizdovat V, Agop M, Luca A Polymers (Basel). 2023; 15(4).

PMID: 36850302 PMC: 9962169. DOI: 10.3390/polym15041018.

Updates on Responsive Drug Delivery Based on Liposome Vehicles for Cancer Treatment.

Nikolova M, Kumar E, Chavali M Pharmaceutics. 2022; 14(10).

PMID: 36297630 PMC: 9608678. DOI: 10.3390/pharmaceutics14102195.

References

Takara K, Hatakeyama H, Kibria G, Ohga N, Hida K, Harashima H . Size-controlled, dual-ligand modified liposomes that target the tumor vasculature show promise for use in drug-resistant cancer therapy. J Control Release. 2012; 162(1):225-32. DOI: 10.1016/j.jconrel.2012.06.019. View

Clevers H . The cancer stem cell: premises, promises and challenges. Nat Med. 2011; 17(3):313-9. DOI: 10.1038/nm.2304. View

Perche F, Patel N, Torchilin V . Accumulation and toxicity of antibody-targeted doxorubicin-loaded PEG-PE micelles in ovarian cancer cell spheroid model. J Control Release. 2012; 164(1):95-102. PMC: 3502646. DOI: 10.1016/j.jconrel.2012.09.003. View

Mehta G, Hsiao A, Ingram M, Luker G, Takayama S . Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy. J Control Release. 2012; 164(2):192-204. PMC: 3436947. DOI: 10.1016/j.jconrel.2012.04.045. View

Wu H, Zhu L, Torchilin V . pH-sensitive poly(histidine)-PEG/DSPE-PEG co-polymer micelles for cytosolic drug delivery. Biomaterials. 2012; 34(4):1213-22. PMC: 3587181. DOI: 10.1016/j.biomaterials.2012.08.072. View

Toriyabe N, Hayashi Y, Harashima H . The transfection activity of R8-modified nanoparticles and siRNA condensation using pH sensitive stearylated-octahistidine. Biomaterials. 2012; 34(4):1337-43. DOI: 10.1016/j.biomaterials.2012.10.043. View

Jiang X, Xin H, Gu J, Xu X, Xia W, Chen S . Solid tumor penetration by integrin-mediated pegylated poly(trimethylene carbonate) nanoparticles loaded with paclitaxel. Biomaterials. 2012; 34(6):1739-46. DOI: 10.1016/j.biomaterials.2012.11.016. View

Yu B, Mao Y, Yuan Y, Yue C, Wang X, Mo X . Targeted drug delivery and cross-linking induced apoptosis with anti-CD37 based dual-ligand immunoliposomes in B chronic lymphocytic leukemia cells. Biomaterials. 2013; 34(26):6185-93. PMC: 3756150. DOI: 10.1016/j.biomaterials.2013.04.063. View

Zhang Q, Tang J, Fu L, Ran R, Liu Y, Yuan M . A pH-responsive α-helical cell penetrating peptide-mediated liposomal delivery system. Biomaterials. 2013; 34(32):7980-93. DOI: 10.1016/j.biomaterials.2013.07.014. View

10.

Hu J, Miura S, Na K, Bae Y . pH-responsive and charge shielded cationic micelle of poly(L-histidine)-block-short branched PEI for acidic cancer treatment. J Control Release. 2013; 172(1):69-76. DOI: 10.1016/j.jconrel.2013.08.007. View

11.

Kunjachan S, Pola R, Gremse F, Theek B, Ehling J, Moeckel D . Passive versus active tumor targeting using RGD- and NGR-modified polymeric nanomedicines. Nano Lett. 2014; 14(2):972-81. PMC: 3940962. DOI: 10.1021/nl404391r. View

12.

Mikhail A, Eetezadi S, Ekdawi S, Stewart J, Allen C . Image-based analysis of the size- and time-dependent penetration of polymeric micelles in multicellular tumor spheroids and tumor xenografts. Int J Pharm. 2014; 464(1-2):168-77. DOI: 10.1016/j.ijpharm.2014.01.010. View

13.

Liu Y, Ran R, Chen J, Kuang Q, Tang J, Mei L . Paclitaxel loaded liposomes decorated with a multifunctional tandem peptide for glioma targeting. Biomaterials. 2014; 35(17):4835-47. DOI: 10.1016/j.biomaterials.2014.02.031. View

14.

Mei L, Fu L, Shi K, Zhang Q, Liu Y, Tang J . Increased tumor targeted delivery using a multistage liposome system functionalized with RGD, TAT and cleavable PEG. Int J Pharm. 2014; 468(1-2):26-38. DOI: 10.1016/j.ijpharm.2014.04.008. View

15.

Zong T, Mei L, Gao H, Cai W, Zhu P, Shi K . Synergistic dual-ligand doxorubicin liposomes improve targeting and therapeutic efficacy of brain glioma in animals. Mol Pharm. 2014; 11(7):2346-57. DOI: 10.1021/mp500057n. View

16.

Pan L, Liu J, He Q, Shi J . MSN-mediated sequential vascular-to-cell nuclear-targeted drug delivery for efficient tumor regression. Adv Mater. 2014; 26(39):6742-8. DOI: 10.1002/adma.201402752. View

17.

Verbeek F, van der Vorst J, Tummers Q, Boonstra M, de Rooij K, Lowik C . Near-infrared fluorescence imaging of both colorectal cancer and ureters using a low-dose integrin targeted probe. Ann Surg Oncol. 2014; 21 Suppl 4:S528-37. PMC: 4128907. DOI: 10.1245/s10434-014-3524-x. View

18.

Folkman J . Role of angiogenesis in tumor growth and metastasis. Semin Oncol. 2003; 29(6 Suppl 16):15-8. DOI: 10.1053/sonc.2002.37263. View

19.

Vaupel P, Kallinowski F, Okunieff P . Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 1989; 49(23):6449-65. View

20.

Pasqualini R, Koivunen E, Ruoslahti E . Alpha v integrins as receptors for tumor targeting by circulating ligands. Nat Biotechnol. 1997; 15(6):542-6. DOI: 10.1038/nbt0697-542. View