Di Zhang, Shuhe Zhang, Baoding Shan, Yihan Zhao, Guangming Jin
Department of Ultrasound, Yanbian University Hospital, No. 1327, Juzi Street, Yanji City, 133000, Jilin Province, China.
Discov Oncol. 2024 Nov 2;15(1):611. doi: 10.1007/s12672-024-01486-z.
To prepare and characterize transferrin (Tf)-modified liposomes (Lipo) encapsulating the photosensitizing agent neoindocyanine green (IR820), and to investigate their effects on breast cancer 4T1 cells as well as in a breast cancer mouse model.
Photosensitive liposomes, IR820@Lipo and Tf-IR820@Lipo, were synthesized using thin film dispersion, with encapsulation efficiency assessed via UV detection. The physicochemical properties were analyzed using transmission electron microscopy (TEM) and particle size analysis. Uptake by breast cancer 4T1 cells was evaluated through confocal laser scanning microscopy and flow cytometry, while cell proliferation inhibition was measured using the CCK8 assay. Differences in intracellular fluorescence intensity were utilized to assess drug aggregation in vivo through small animal imaging techniques. The anticancer efficacy and potential side effects of the formulations were examined through pharmacodynamic studies conducted in vivo.
The mean particle sizes of IR820@Lipo and Tf-IR820@Lipo were found to be 84.30 ± 15.66 nm and 116.20 ± 14.68 nm respectively, with zeta potentials of -8.21 ± 2.06 mV for IR820@Lipo and -5.23 ± 1.19 mV for Tf-IR820@Lipo; TEM revealed that the liposomes exhibited a spheroid morphology with uniform distribution across samples; encapsulation efficiencies reached 86.38 ± 0.99% for IR820@Lipo and an impressive 93.81 ± 1.06% for Tf-IR820@Lipo; notably, Tf-IR820@Lipo significantly inhibited proliferation while promoting apoptosis of the 4T1 cells upon laser irradiation; reactive oxygen species (ROS) detection indicated enhanced fluorescence intensity within the treated cells under light exposure when utilizing both formulations; in vivo experiments demonstrated tumor accumulation of both IR820@Lipo and Tf-IR820@Lipo, indicating effective tumor targeting within a breast cancer mouse model; pharmacodynamic assessments revealed that Tf-IR820@Lipo exhibited superior inhibitory effects against breast cancer without causing liver or kidney dysfunctions in mice nor presenting significant toxic side effects overall.
Given its high targeting capability, potent efficacy, and low toxicity profile, Tf-IR820@Lipo holds promise as a novel therapeutic agent for breast cancer treatment when combined with photodynamic therapy (PDT), potentially offering new avenues for patient management.
制备并表征包裹光敏剂新吲哚菁绿（IR820）的转铁蛋白（Tf）修饰脂质体（Lipo），并研究其对乳腺癌4T1细胞以及乳腺癌小鼠模型的作用。
采用薄膜分散法合成光敏脂质体IR820@Lipo和Tf-IR820@Lipo，通过紫外检测评估包封率。利用透射电子显微镜（TEM）和粒度分析对其理化性质进行分析。通过共聚焦激光扫描显微镜和流式细胞术评估乳腺癌4T1细胞对其的摄取，同时使用CCK8法测定细胞增殖抑制情况。利用细胞内荧光强度差异，通过小动物成像技术评估体内药物聚集情况。通过体内药效学研究考察制剂的抗癌疗效和潜在副作用。
发现IR820@Lipo和Tf-IR820@Lipo的平均粒径分别为84.30±15.66nm和116.20±14.68nm，IR820@Lipo的ζ电位为-8.21±2.06mV，Tf-IR820@Lipo的ζ电位为-5.23±1.19mV；TEM显示脂质体呈球形，样品间分布均匀；IR820@Lipo的包封率达到86.38±0.99%，Tf-IR820@Lipo的包封率高达93.81±1.06%；值得注意的是，激光照射后，Tf-IR820@Lipo显著抑制4T1细胞增殖并促进其凋亡；活性氧（ROS）检测表明，使用两种制剂时，光照处理的细胞内荧光强度增强；体内实验表明IR820@Lipo和Tf-IR820@Lipo均在肿瘤部位蓄积，表明在乳腺癌小鼠模型中具有有效的肿瘤靶向性；药效学评估显示，Tf-IR820@Lipo对乳腺癌具有优异的抑制作用，且不会导致小鼠肝肾功能障碍，总体上也未表现出明显的毒副作用。
鉴于其高靶向性、强效疗效和低毒性，Tf-IR820@Lipo与光动力疗法（PDT）联合使用时有望成为一种新型的乳腺癌治疗药物，可能为患者管理提供新途径。
