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International Journal of Pharmaceutics

International Journal of Pharmaceutics

IF: 5.3
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An antigen/chemotherapy co-loaded DNA nanocube inserts into tumor cell plasma membrane and enhances chemo-and immunotherapy

Published:9 December 2024 DOI: 10.1016/j.ijpharm.2024.125068 PMID: 39662859
Jun Cao,?Junhong Sun,?Yuzhen Zhang,?Zhuolin Dong,?Mengru Li,?Fenfen Liu,?Ayesha Younas,?Nan Zhang,?Yibing Chen

Abstract

Breast cancer is the most frequently diagnosed female cancer. Combined chemo- and immunotherapies have been extensively explored to treat breast cancer. To improve the efficacy of the combined therapies, this study designed a hollow DNA nanocube with four cholesterol anchors (C2.2) that could be inserted into breast cancer cell plasma membrane. A model antigen-ovalbumin (OVA257-264) was further conjugated to C2.2 to construct C2.2-OVA and a model chemotherapy-Doxorubicin (DOX) was also loaded to C2.2-OVA to prepare DOX@C2.2-OVA for the combined chemo- and immunotherapy to treat breast cancer. C2.2, C2.2-OVA, and DOX@C2.2-OVA were successfully prepared and possessed square-like shape and small size. C2.2 and C2.2-OVA could be anchored in breast cancer cell plasma membrane for at least 10?h. C2.2-OVA demonstrated the significantly higher activation rates of DC cells than free OVA. Although C2.2 showed no cytotoxicity, C2.2 increased the potency of 5-FU and carboplatin to MCF-7 and 4?T1 breast cancer cells. DOX@C2.2-OVA treatment to 4?T1 tumor in vivo showed the significant reduction of tumor size and weight, and resulted in more DCs and CD8+ T cells in 4?T1 tumor. In summary, DOX@C2.2-OVA that could be inserted into tumor cell plasma membrane enhanced the combined chemo- and immunotherapy for the breast cancer treatment.

Substances (13)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Acetic acid 64-19-7 C2H4O2 1774 suppliers $10.00-$9280.00
Tris(hydroxymethyl)aminomethane 77-86-1 C4H11NO3 1524 suppliers $5.00-$8920.00
Ethylenediaminetetraacetic acid 60-00-4 C10H16N2O8 1438 suppliers $6.00-$6397.62
5-Fluorouracil 51-21-8 C4H3FN2O2 1098 suppliers $5.00-$2970.00
Urea 57-13-6 CH4N2O 1046 suppliers $5.00-$9960.00
Ammonium persulfate 7727-54-0 H8N2O8S2 767 suppliers $10.16-$3100.00
Trypsin 9002-07-7 C35H47N7O10 737 suppliers $19.90-$28880.00
N,N,N',N'-Tetramethylethylenediamine 110-18-9 C6H16N2 735 suppliers $7.62-$2750.00
Agarose 9012-36-6 C10H15N3O3 729 suppliers $18.53-$3090.00
Acrylamide 79-06-1 C3H5NO 692 suppliers $12.70-$1772.00

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