Campbell Robert B, Fukumura Dai, Brown Edward B, Mazzola Laureen M, Izumi Yotaro, Jain Rakesh K, Torchilin Vladimir P, Munn Lance L
Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Cancer Res. 2002 Dec 1;62(23):6831-6.
Tumor vessels possess unique physiological features that might be exploited for improving drug delivery. In the present study, we investigate the possibility of modifying polyethylene glycol-ylated liposome cationic charge of polyethylene glycol coated liposomes to optimize delivery to tumor vessels using biodistribution studies and intravital microscopy. The majority of liposomes accumulated in the liver, and increasing charge resulted in lower retention in the spleen and blood. Although overall tumor uptake was not affected by charge in the biodistribution studies, intravital microscopy showed that increasing the charge content from 10 to 50 mol % doubled the accumulation of liposomes in tumor vessels, suggesting a change in intratumor distribution; no significant effect of charge on interstitial accumulation could be detected, possibly attributable to spatial heterogeneity. Increased vascular accumulation of cationic liposomes was similar in two different tumor types and sites. Our results suggest that optimizing physicochemical properties of liposomes that exploit physiological features of tumors and control the intratumor distribution of these drug carriers should improve vascular-specific delivery.
肿瘤血管具有独特的生理特征，可用于改善药物递送。在本研究中，我们利用生物分布研究和活体显微镜检查，研究了改变聚乙二醇化脂质体（聚乙二醇包被脂质体）的阳离子电荷，以优化向肿瘤血管递送的可能性。大多数脂质体积聚在肝脏中，电荷增加导致在脾脏和血液中的滞留减少。尽管在生物分布研究中，总体肿瘤摄取不受电荷影响，但活体显微镜检查显示，将电荷含量从10 mol%增加到50 mol%，脂质体在肿瘤血管中的积累增加了一倍，这表明肿瘤内分布发生了变化；未检测到电荷对间质积累有显著影响，这可能归因于空间异质性。阳离子脂质体在两种不同肿瘤类型和部位的血管积累增加情况相似。我们的结果表明，优化利用肿瘤生理特征并控制这些药物载体在肿瘤内分布的脂质体的物理化学性质，应能改善血管特异性递送。
