Snyder John W, Greco William R, Bellnier David A, Vaughan Lurine, Henderson Barbara W
The Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Cancer Res. 2003 Dec 1;63(23):8126-31.
Using the photosensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a, we have determined that photodynamic therapy (PDT) can be used to facilitate the delivery of macromolecular agents. PDT regimens that use low fluences and fluence rates were the most successful. This effect was demonstrated for fluorescent microspheres with diameters ranging from 0.1 to 2 microm. Such treatment given immediately before administration of Doxil, a liposomally encapsulated formulation of doxorubicin with an average diameter of 0.1 microm, significantly enhanced its accumulation in transplanted murine Colo 26 tumors. The combination of PDT and Doxil led to a highly significant potentiation in tumor control without concomitant enhancement of systemic or local toxicity. Interestingly, concentration-effect modeling suggested that the enhanced cure rate was greater than what was predicted based on the increase in intratumor Doxil concentration. In summary, we have developed a novel PDT treatment that enhances the delivery and efficacy of macromolecule-based cancer therapies such as Doxil.
使用光敏剂2-[1-己氧基乙基]-2-去乙烯基焦脱镁叶绿酸-a，我们已确定光动力疗法（PDT）可用于促进大分子药物的递送。使用低光通量和光通量率的PDT方案最为成功。这种效果在直径范围为0.1至2微米的荧光微球中得到了证明。在给予平均直径为0.1微米的脂质体包裹阿霉素制剂Doxil之前立即进行这种治疗，可显著增强其在移植的小鼠Colo 26肿瘤中的蓄积。PDT与Doxil联合使用可在肿瘤控制方面产生高度显著的增效作用，而不会同时增强全身或局部毒性。有趣的是，浓度-效应模型表明，提高的治愈率高于根据肿瘤内Doxil浓度增加所预测的数值。总之，我们开发了一种新型的PDT治疗方法，可增强基于大分子的癌症治疗药物（如Doxil）的递送和疗效。
