SREKA-targeted liposomes for highly metastatic breast cancer therapy

Drug Deliv. 2023 Dec;30(1):2174210. doi: 10.1080/10717544.2023.2174210.


Chemotherapy is still a leading therapeutic approach in various tumor types that is often accompanied by a poor prognosis because of metastases. PEGylated liposomes with CREKA targeting moiety are well-known therapeutic agents, especially in highly metastatic experimental models. CREKA specifically targets tumor-associated ECM, which is present at the primary, as well as metastatic tumor sites. To better understand the function of the targeting moieties, we decided to design various liposome formulations with different amounts of targeting moiety attached to their DSPE-PEG molecules. Moreover, a new tumor-homing pentapeptide (SREKA) was designed, and a novel conjugation strategy between SREKA and DSPE-PEGs. First, the in vitro proliferation inhibition of drug-loaded liposomes and the cellular uptake of their cargo were investigated. Afterward, liposome stability in murine blood and drug accumulation in different tissues were measured. Furthermore, in vivo tumor growth, and metastasis inhibition potencies of the different liposome formulations were examined. According to our comparative studies, SREKA-liposomes have a uniform phenotype after formulation and have similar characteristics and tumor-homing capabilities to CREKA-liposomes. However, the exchange of the N-terminal cysteine to serine during conjugation results in a higher production yield and better stability upon conjugation to DSPE-PEGs. We also showed that SREKA-liposomes have significant inhibition on primary tumor growth and metastasis incidence; furthermore, increase the survival rate of tumor-bearing mice. Besides, we provide evidence that the amount of targeting moiety attached to DSPE-PEGs is largely responsible for the stability of liposomes, therefore it plays an important role in toxicity and targeting.

Keywords: SREKA peptide; Targeted cancer therapy; nanocarriers; tumor metastasis.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Drug Delivery Systems / methods
  • Liposomes* / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms* / drug therapy
  • Polyethylene Glycols / chemistry


  • Liposomes
  • Polyethylene Glycols

Grants and funding

This work was supported by grants from European Union′s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 861316. The authors acknowledge financial support from the National Laboratories Excellence program (under the National Tumorbiology Laboratory Project (2022-2.1.1-NL-2022-00010)) and the Hungarian Thematic Excellence Programme (TKP2021-EGA-44). The research within Project No. VEKOP-2.3.3-15-2017-00020 was supported by the European Union and the State of Hungary and was co-financed by the European Regional Development Fund. We also gained funding from the Hungarian Scientific Research Fund (NKFIH-OTKA) grant K119552 and by project no. 2018-1.2.1-NKP-2018-00005 implemented with the support provided by the National Research, Development and Innovation Fund of Hungary, and within the framework of the ELTE Thematic Excellence Programme 2020, National Challenges Subprogramme – TKP2020-NKA-06, supported by the Hungarian Ministry for Innovation and Technology.