Intracellular distribution of doxorubicin (DOX) and its squalenoylated (SQ-DOX) nanoparticles (NPs) form in murine lung carcinoma M109 and human breast carcinoma MDA-MB-231 cells was investigated by Raman microspectroscopy. Pharmacological data showed that DOX induced higher cytotoxic effect than SQ-DOX NPs. Raman data were obtained using single-point measurements and imaging on the whole cell areas. These data showed that after DOX treatment at 1 μM, the spectral features of DOX were not detected in the M109 cell cytoplasm and nucleus. However, the intracellular distribution of SQ-DOX NPs was higher than DOX in the same conditions. In addition, SQ-DOX NPs were localized into both cell cytoplasm and nucleus. After 5 μM treatment, Raman bands of DOX at 1211 and 1241 cm⁻¹ were detected in the nucleus. Moreover, the intensity ratio of these bands decreased, indicating DOX intercalation into DNA. However, after treatment with SQ-DOX NPs, the intensity of these Raman bands increased. Interestingly, with SQ-DOX NPs, the intensity of 1210/1241 cm⁻¹ ratio was higher suggesting a lower fraction of intercalated DOX in DNA and higher amount of non-hydrolyzed SQ-DOX. Raman imaging data confirm this subcellular localization of these drugs in both M109 and MDA-MB-231 cells. These finding brings new insights to the cellular characterization of anticancer drugs at the molecular level, particularly in the field of nanomedicine.

通过拉曼显微光谱研究了多柔比星 (DOX) 及其角鲨烯酰化 (SQ-DOX) 纳米颗粒 (NPs) 在小鼠肺癌 M109 和人乳腺癌 MDA-MB-231 细胞中的细胞内分布。药理学数据表明，DOX 诱导的细胞毒作用高于 SQ-DOX NPs。拉曼数据是使用单点测量和整个细胞区域的成像获得的。这些数据表明，在 1 μM DOX 处理后，在 M109 细胞的细胞质和细胞核中未检测到 DOX 的光谱特征。然而，在相同条件下，SQ-DOX NPs 的细胞内分布高于 DOX。此外，SQ-DOX NPs 定位于细胞质和细胞核中。5 μM 处理后，DOX 在 1211 和 1241 cm ^{-1的拉曼谱带}在细胞核中检测到。此外，这些条带的强度比降低，表明 DOX 嵌入 DNA。然而，在用 SQ-DOX NPs 处理后，这些拉曼谱带的强度增加了。有趣的是，对于 SQ-DOX NPs，1210/1241 cm ^-1比率的强度更高，表明 DNA 中插入的 DOX 分数较低，未水解的 SQ-DOX 的量较高。拉曼成像数据证实了这些药物在 M109 和 MDA-MB-231 细胞中的这种亚细胞定位。这些发现为分子水平的抗癌药物的细胞表征带来了新的见解，特别是在纳米医学领域。