The size of nanoliposome-encapsulated drugs significantly affects their therapeutic efficacy, biodistribution, targeting ability, and toxicity profile for the cancer treatment. In the present study, the biodistribution and anti-tumoral activity of PEGylated liposomal Doxorubicin (PLD) formulations with different sizes were investigated. First, 100, 200, and 400 nm PLDs were prepared by remote loading procedure and characterised for their size, zeta potential, encapsulation efficacy, and release properties. Then, in vitro cellular uptake and cytotoxicity were studied by flow cytometry and MTT assay, and compared with commercially available PLD Caelyx® . In vivo studies were applied on BALB/c mice bearing C26 colon carcinoma. The cytotoxicity and cellular uptake tests did not demonstrate any statistically significant differences between PLDs. The biodistribution results showed that Caelyx® and 100 nm liposomal formulations had the most doxorubicin (Dox) accumulation in the tumour tissue and, as a result, considerably suppressed tumour growth compared with 200 and 400 nm PLDs. In contrast, larger nanoparticles (200 and 400 nm formulations) had more accumulation in the liver and spleen. This study revealed that 90 nm Caelyx® biodistribution profile led to the stronger anti-tumour activity of the drug and hence significant survival extension, and showed the importance of vesicle size in the targeting of nanoparticles to the tumour microenvironment for the treatment of cancer.

中文翻译：

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大小在聚乙二醇化脂质体阿霉素生物分布和抗肿瘤活性中的作用。

纳米脂质体包裹药物的大小显着影响其在癌症治疗中的治疗效果、生物分布、靶向能力和毒性特征。在本研究中，研究了不同大小的聚乙二醇化脂质体多柔比星 (PLD) 制剂的生物分布和抗肿瘤活性。首先，通过远程加载程序制备 100、200 和 400 nm PLD，并对其尺寸、zeta 电位、封装功效和释放特性进行表征。然后，通过流式细胞仪和 MTT 法研究体外细胞摄取和细胞毒性，并与市售的 PLD Caelyx® 进行比较。体内研究应用于携带 C26 结肠癌的 BALB/c 小鼠。细胞毒性和细胞摄取测试没有证明 PLD 之间有任何统计学上的显着差异。生物分布结果表明，Caelyx® 和 100 nm 脂质体制剂在肿瘤组织中的多柔比星 (Dox) 积累最多，因此与 200 和 400 nm PLD 相比，可显着抑制肿瘤生长。相比之下，较大的纳米颗粒（200 和 400 nm 制剂）在肝脏和脾脏中积累更多。该研究表明，90 nm Caelyx® 生物分布曲线导致药物具有更强的抗肿瘤活性，从而显着延长生存期，并显示了囊泡大小在将纳米颗粒靶向肿瘤微环境以治疗癌症中的重要性。与 200 和 400 nm PLD 相比，显着抑制了肿瘤的生长。相比之下，较大的纳米颗粒（200 和 400 nm 制剂）在肝脏和脾脏中积累更多。该研究表明，90 nm Caelyx® 生物分布曲线导致药物具有更强的抗肿瘤活性，从而显着延长生存期，并显示了囊泡大小在将纳米颗粒靶向肿瘤微环境以治疗癌症中的重要性。与 200 和 400 nm PLD 相比，显着抑制了肿瘤的生长。相比之下，较大的纳米颗粒（200 和 400 nm 制剂）在肝脏和脾脏中积累更多。该研究表明，90 nm Caelyx® 生物分布曲线导致药物具有更强的抗肿瘤活性，从而显着延长生存期，并显示了囊泡大小在将纳米颗粒靶向肿瘤微环境以治疗癌症中的重要性。