Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland.
Mol Pharm. 2022 Aug 1;19(8):2818-2831. doi: 10.1021/acs.molpharmaceut.2c00182. Epub 2022 Jul 18.
Here, we propose tailored lipid liquid-crystalline carriers (cubosomes), which incorporate an anticancer drug (doxorubicin) and complexed short-lived α-emitter (bismuth-213), as a strategy to obtain more effective action toward the cancer cells. Cubosomes were formulated with doxorubicin (DOX) and an amphiphilic ligand (DOTAGA-OA), which forms stable complexes with Bi radionuclide. The behavior of DOX incorporated into the carrier together with the chelating agent was investigated, and the drug liberation profile was determined. The experiments revealed that the presence of the DOTAGA-OA ligand affects the activity of DOX when they are incorporated into the same carrier. This unexpected influence was explained based on the results of release studies, which proved the contribution of electrostatics in molecular interactions between the positively charged DOX and negatively charged DOTAGA-OA in acidic and neutral solutions. A significant decrease in the viability of HeLa cancer cells was achieved using sequential cell exposure: first to the radiolabeled cubosomes containing Bi complex and next to DOX-doped cubosomes. Therefore, the sequential procedure for the delivery of both drugs encapsulated in cubosomes is suggested for further biological and studies.
在这里，我们提出了一种定制的脂质液晶载体（立方载体），其中包含一种抗癌药物（阿霉素）和短寿命的α发射体（铋-213），作为获得更有效针对癌细胞作用的策略。立方载体由阿霉素（DOX）和两亲配体（DOTAGA-OA）组成，与 Bi 放射性核素形成稳定的配合物。研究了载体内 DOX 的行为以及与螯合剂一起的药物释放情况，并确定了药物释放情况。实验表明，当 DOX 与配体一起掺入同一载体时，配体的存在会影响 DOX 的活性。这种意外的影响可以根据释放研究的结果来解释，该结果证明了在酸性和中性溶液中，带正电荷的 DOX 和带负电荷的 DOTAGA-OA 之间的分子相互作用中静电的贡献。通过顺序细胞暴露，即首先暴露于含有 Bi 配合物的放射性标记的立方载体，然后暴露于 DOX 掺杂的立方载体，成功实现了 HeLa 癌细胞活力的显著降低。因此，建议对立方载体中封装的两种药物进行顺序递送来进行进一步的生物学和研究。
