Evaluation of the effect of SMA-pirarubicin micelles on colorectal cancer liver metastases and of hyperbaric oxygen in CBA mice
Evaluation of the effect of SMA-pirarubicin micelles on colorectal cancer liver metastases and of hyperbaric oxygen in CBA mice
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DOI：
10.1080/10611860701499839
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发表时间：
2007-01-01
影响因子：
4.5
通讯作者：
Christophi, Chris
中科院分区：
文献类型：
--
作者：
Daruwalla, Jurstine;Greish, Khaled;Christophi, Chris
四氢吡喃霉素（THP 或吡柔比星）通过多种机制破坏肿瘤；其中之一涉及ROS的产生，ROS的产生需要分子氧。 SNLN与吡柔比星（SMA-pirarubicin）形成稳定的自组装缔合胶束（SMA-pirarubicin），并赋予吡柔比星大分子特征。这种胶束大分子药物通过 EPR 效应选择性地递送至实体瘤，其在肿瘤中的优先积累抑制了全身毒性，同时其在肿瘤部位的长时间高浓度增强了其疗效，与游离的吡柔比星相比更高。在 HBO 下施用 SMA-吡柔比星胶束可以进一步增强分子氧的输送，促进肿瘤选择性生成 ROS，从而增强其抗肿瘤效力。在这项研究中，我们评估了 SMA-吡柔比星胶束作为单一药物或与 HBO 联合使用在小鼠转移性结直肠癌模型中的疗效。在最大耐受剂量或低于最大耐受剂量时，SMA-吡柔比星可显着减少转移性肿瘤结节，并且比游离吡柔比星更有效。数据还表明 HBO 与胶束蒽环类药物联合治疗的潜在益处。
Tetrahydropyranyladriamycin (THP or pirarubicin) destroys tumors via several mechanisms; one of which involves the production of ROS that requires molecular oxygen for its generation. SNLN forms stable self-assembled associated micelles with pirarubicin (SMA-pirarubicin), and confers macromolecular characteristics to pirarubicin. This micellar macromolecular drug is selectively delivered to solid tumors via the EPR effect and its preferential tumor accumulation suppresses the systemic toxicity whilst its prolonged high concentration at the site of tumor enhances its efficacy much higher compared to free pirarubicin. Administration of SMA-pirarubicin micelle under HBO can further enhance the delivery of molecular oxygen that facilitates tumor selective generation of ROS, thus augmenting its antitumor potency. In this study, we evaluated the efficacy of SMA-pirarubicin micelles either as single drug or in combination with HBO in a mouse metastatic colorectal cancer model. At or below the maximum tolerated dose, SMA-pirarubicin remarkably reduced metastatic tumor nodules and it was far more effective than free pirarubicin. The data also suggests a potential benefit of combined therapy of HBO with micellar anthracyclins.