Enhanced chemoimmunotherapy of breast cancer in mice by apolipoprotein A1-modified doxorubicin liposomes combined with interleukin-21

Abstract

Backgroud: Breast cancer is a prevalent malignancy among women, with triple-negative breast cancer (TNBC) comprising approximately 15–20% of all cases, possessing high invasiveness, drug resistance and poor prognosis. Chemotherapy, the main treatment for TNBC, is limited by toxicity and drug resistance. Apolipoprotein A1 modified doxorubicin liposome (ApoA1-lip/Dox) was constructed in our previous study, with promising anti-tumour effect and improved safety been proved. However, during long-term administration, the problem of cumulative toxicity and insufficient tumour inhibition is still inevitable. Interleukin-21 is a small molecule protein secreted by T cells with various immune regulatory functions. IL-21 has significantly curative effects in numerous solid tumours, but it has the disadvantages of low response rate and short half-life. The combination of chemotherapy and immunotherapy has received increasing attention.

Purpose: In this study, ApoA1 drug loading system and long-acting IL-21 are innovatively combined for tumour treatment.

Methods: We combined ApoA1-lip/Dox and IL-21 for treatment and evaluated their impact on tumor-infiltrating lymphocytes and CD8⁺ T and NK cell cytotoxicity.

Results: Combined administration significantly improved the tumour-infiltrating lymphocytes and enhanced the cytotoxicity of CD8⁺ T and NK cells. The combination of ApoA1-lip/Dox and IL-21 exhibits significantly enhanced anti-tumour efficacy with lower toxicity of ApoA1-lip/Dox, providing a new strategy for TNBC treatment with enhanced anti-tumour response and reduced toxicity.

Keywords:

• Apolipoprotein A1
• doxorubicin liposome
• interleukin-21
• triple negative breast cancer
• combination therapy

Ethics statement

The animal study was reviewed and approved bySSS the Animal Ethics Committee of the School of Pharmacy, Fudan University.

Author contributions

DA, PH and HL contributed equally to this work. Conceptualisation, DA, MF and XL; methodology, DA, PH and HL; software, DA, PH and HL; validation, RW, XY and NC; investigation, NC and XG; resources, HL; data curation, RW and XL; writing—original draft preparation, DA, PH and HL; writing—review and editing, MF and XL; visualisation, DA; supervision, MF and XL; project administration, MF and XL. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article.

Additional information

Funding

This research received no external funding.