Yatvin M B, Mühlensiepen H, Porschen W, Weinstein J N, Feinendegen L E
Cancer Res. 1981 May;41(5):1602-7.
In an attempt to optimize the chemotherapeutic treatment of mouse tumor Sarcoma 180, liposomes containing cis-dichlorodiammineplatinum(II) (PDD), having transition temperatures of few degrees higher than the rectal temperature of mice, were used in combination with local hyperthermia. The uptake of radioactive PDD by tumors heated for 1 hr at 42 degrees was almost four-fold greater when the drug was associated in liposomes than if administered as free drug. Uptake of liposome-administered radioactive platinum by liver was twice that obtained with free PDD, whereas its incorporation by the kidney was the same by either method of drug administration. The effect of various combinations of hyperthermia, drug-containing liposomes, and free PDD on tumor growth was also studied. Treatment with liposome-associated PDD plus local heating resulted in a dose-modifying factor of 7 when compared with free drug and no hyperthermia. The dose-modifying factor was 2.5 when PDD liposomes and heat were compared within free drug and heat. Thus, PDD could be specifically released from liposomes by heat and resulted in both a greater drug uptake and a delayed tumor growth following treatment. Potential normal tissue toxicity problems, however, still need to be resolved before clinical application of this combined modality will be possible.
为了优化对小鼠肉瘤180的化疗治疗，使用了含有顺二氯二氨铂（II）（PDD）的脂质体，其相变温度比小鼠直肠温度高几度，并与局部热疗联合使用。当药物与脂质体结合时，在42℃加热1小时的肿瘤对放射性PDD的摄取量几乎是游离药物给药时的四倍。脂质体给药的放射性铂在肝脏中的摄取量是游离PDD的两倍，而通过两种给药方法其在肾脏中的掺入量相同。还研究了热疗、含药脂质体和游离PDD的各种组合对肿瘤生长的影响。与游离药物且无热疗相比，脂质体结合的PDD加局部加热治疗产生的剂量修正因子为7。当在游离药物和热疗条件下比较PDD脂质体和热疗时，剂量修正因子为2.5。因此，PDD可通过加热从脂质体中特异性释放，导致治疗后药物摄取量增加和肿瘤生长延迟。然而，在这种联合治疗方法能够临床应用之前，潜在的正常组织毒性问题仍需解决。
