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Carrier-free doxorubicin/rhein supramolecular co-assembly for cancer therapy

阿霉素 体内 心脏毒性 化学 生物物理学 药物输送 药理学 癌细胞 癌症研究 癌症 医学 毒性 内科学 化疗 生物 有机化学 生物技术
作者
Peng Bai,Dan Li,Mingsong Shi,Jing Wang,Minghai Tang,Neng Qiu,Jiaolin Wen
出处
期刊:Journal of Drug Delivery Science and Technology [Elsevier]
卷期号:89: 105030-105030 被引量:1
标识
DOI:10.1016/j.jddst.2023.105030
摘要

Cardiotoxicity remains a challenge for the clinical application of doxorubicin. Here, a carrier-free self-assembled supramolecular named Doxorubicin-Rhein supramolecular (D-R Supra) was prepared by π-π stacking of Rhein and doxorubicin with green procedures. Molecular dynamics (MD) simulations showed that DOX molecules aggregated around Rhein molecules through intermolecular forces, resulting in a supramolecule with a particle size of about 200 nm and a DOX loading efficiency of 81.13 ± 4.70% and Rhein loading efficiency of up to 94.24 ± 3.28%. These supramolecules not only showed a sustained release effect compared with free drugs but also exhibited pH-dependent drug release profile. Notably, the blood circulation of DOX in this particle was significantly prolonged (>34 h) with 4.89 times that of free DOX, and the in vivo clearance rate was only one-third of that of free DOX. Tissue distribution experiments demonstrated that D-R Supra significantly reduced DOX distribution in heart tissue, and in vivo experiments demonstrated that D-R Supra significantly reduced inflammatory cell infiltration and connective tissue hyperplasia of heart tissue. In addition, the supramolecules can significantly inhibit tumor growth and prolong the survival time in comparison with free DOX in a highly malignant BL-2 secondary transplantation mouse model with clinical patient symptoms of Ph+ B-cell acute lymphoblastic leukemia (B-ALL). Therefore, the proposed excipient-free strategy has a significant effect of reducing the toxicity and increasing the efficiency of DOX and may be a promising delivery system for cancer therapy.
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