Doxorubicin

Doxorubicin(DOX), also known as adriamycin, is a compound of the anthracycline class that has the broadest spectrum of activity^[1]. Doxorubicin inhibits topoisomerase Ⅱ and topoisomerase Ⅰ with IC⁵⁰ of 2.67μM and 0.8μM, respectively^[2,3]. It is widely used for the treatment of various solid tumors via interacting with deoxyribonucleic acid, but it is limited in the clinical application due to severe side effect^[4]

Doxorubicin can be loaded into liposomes by transmembrane pH gradient method to get high encapsulation efficiency with high drug/lipid ratio. Liposomal doxorubicin is a successful clinical formulation, and also a perfect model drug system for cancer-therapy research^[5]. A considerable amount of doxorubicin can accumulate in human placental tissue. Both doxorubicin and its pH-sensitive liposomal formulation, L-Doxorubicin, are efficiently internalized by human trophoblastic BeWo cells and that doxorubicin accumulates in placental tissue so that decrease the exposure of fetal^[6]

Doxorubicin combines with cobimetinib at sublethal dose completely arrested osteosarcoma growth. Targeted MEK inhibition by cobimetinib enhances doxorubicin’s efficacy in osteosarcoma models^[7]. Doxorubicin is frequently used as an adjuvant chemotherapeutic agent for breast cancer. Silk films loaded with doxorubicin provide locoregional control of human breast cancer in vivo. By manipulating silk crystallinity or β-sheet content, the doxorubicin release rate could be controlled. Both soluble and stabilised silk films loaded with doxorubicin had a significantly greater primary tumour response than the equivalent dose of doxorubicin administered intravenously in the absence of the silk film carrier. The future use of this approach for localised chemotherapy is promising^[8]

References:
[1].Escoffre JM, Piron J, et al. Doxorubicin delivery into tumor cells with ultrasound and microbubbles. Mol Pharm. 2011;8(3):799-806.
[2].Rhee HK, Park HJ, et al. Synthesis, cytotoxicity, and DNA topoisomerase II inhibitory activity of benzofuroquinolinediones. Bioorg Med Chem. 2007 Feb 15;15(4):1651-8.
[3].Foglesong PD, Reckord C, Swink S. Doxorubicin inhibits human DNA topoisomerase I. Cancer Chemother Pharmacol. 1992;30(2):123-5.
[4].Jie L, Lang D, et al. Superparamagnetic Iron Oxide Nanoparticles/Doxorubicin-Loaded Starch-Octanoic Micelles for Targeted Tumor Therapy. J Nanosci Nanotechnol. 2019;19(9):5456-5462.
[5].Soininen SK, Repo JK, et al. Human placental cell and tissue uptake of doxorubicin and its liposomal formulations. Toxicol Lett. 2015;239(2):108-114.
[6].Niu G, Cogburn B, et al. Preparation and characterization of doxorubicin liposomes. Methods Mol Biol. 2010;624:211-219.
[7].Seib FP, Kaplan DL. Doxorubicin-loaded silk films: drug-silk interactions and in vivo performance in human orthotopic breast cancer. Biomaterials. 2012;33(33):8442-8450.
[8]. Ma L, Xu Y, Xu X. Targeted MEK inhibition by cobimetinib enhances doxorubicin's efficacy in osteosarcoma models. Biochem Biophys Res Commun. 2020;529(3):622-628.

多柔比星（Doxorubicin,简称DOX）,也被称为阿霉素,是一种蒽环类化合物,具有最广泛的活性谱^[1]。DOX通过抑制拓扑异构酶Ⅱ和拓扑异构酶Ⅰ来发挥作用,其IC50分别为2.67μM和0.8μM^[2,3]。它广泛用于治疗各种实体肿瘤,并与脱氧核糖核酸相互作用,但由于严重的副作用,在临床应用中受到限制^[4]。

多柔比星可以通过跨膜pH梯度法装载到脂质体中,以高药物/脂质比获取高的封装效率。脂质体多柔比星是一种成功的临床制剂,也是癌症治疗研究的完美模型药物系统[5]。相当数量的多柔比星可以在人类胎盘组织中积累。多柔比星及其pH敏感性脂质体配方L-Doxorubicin都能够有效地内化到人类滋养层BeWo细胞中,并且多柔比星会在胎盘组织中积累,从而降低了胎儿暴露[6]。

多柔比星与可比替尼在亚致死剂量下结合,完全阻止了骨肉瘤的生长。通过可比替尼靶向抑制MEK增强了多柔比星在骨肉瘤模型中的功效。多柔比星常被用作乳腺癌辅助化疗药物。装载有多柔比星的丝素膜能够提供体内人类乳腺癌局部控制。通过调节丝素晶态或β-折叠含量,可以控制多柔比星释放速率。与不带丝素载体的等效剂量静脉注射相比,既溶解性又稳定的装载有多柔比星的丝素膜具有显着更大的原发肿瘤反应。这种方法未来在局部化学治疗方面具有很大潜力。