Development of a Selective Tumor-Targeted Drug Delivery System: Hydroxypropyl-Acrylamide Polymer-Conjugated Pirarubicin (P-THP) for Pediatric Solid Tumors.
Development of a Selective Tumor-Targeted Drug Delivery System: Hydroxypropyl-Acrylamide Polymer-Conjugated Pirarubicin (P-THP) for Pediatric Solid Tumors.
复制标题
DOI：
10.3390/cancers13153698
复制
发表时间：
2021-07-23
期刊：
影响因子：
5.2
通讯作者：
Maeda H
中科院分区：
文献类型：
--
作者：
Makimoto A;Fang J;Maeda H
羟丙基丙烯酰胺聚合物偶联吡拉西坦（P-THP）是一种新型的聚合物偶联抗癌药物，理论上通过增强的渗透性和保留（EPR）效应具有高度的肿瘤特异性分布。虽然蒽环类药物在大多数儿科实体瘤的治疗中非常重要，但P-THP可能在新诊断和难治性/复发性儿科癌症中作为常规蒽环类药物的毒性较小且更有效的替代品。大多数儿童癌症对化疗高度敏感，细胞毒性化疗一直是治疗的主要手段。蒽环类药物对大多数类型的儿童癌症非常有效，如神经母细胞瘤、肝母细胞瘤、肾母细胞瘤、横纹肌肉瘤、尤文肉瘤等。然而，急性和慢性心脏毒性，蒽环类药物使用的主要缺点之一，限制了它们的实用性和有效性。羟丙基丙烯酰胺聚合物偶联的吡拉西坦（P-THP），其通过增强的渗透性和保留（EPR）效应高度选择性地靶向肿瘤组织，并且其次将活性吡拉西坦分子快速释放到肿瘤周围的酸性环境中。虽然，后者很少发生在正常组织周围的非酸性环境中。这种机制有可能最大限度地减少急性和慢性毒性，包括心脏毒性，以及通过与活性分子的肿瘤靶向积累和可能的剂量递增的协同作用，最大限度地提高化疗的疗效。在给定的方案中，简单地用P-THP代替阿霉素可以改善蒽环类药物敏感的儿科癌症的结局，而不良反应的风险很小，如心脏毒性。由于癌症是一种动态疾病，在其病程期间显示出肿瘤内异质性，因此有必要继续平行开发细胞毒性剂和分子靶向剂，以找到可能更有效的治疗方法。
Hydroxypropyl acrylamide polymer-conjugated pirarubicin (P-THP), an innovative polymer-conjugated anticancer agent, theoretically has highly tumor-specific distribution via the enhanced permeability and retention (EPR) effect. While anthracyclines are extremely important in the treatment of most pediatric solid tumors, P-THP may serve as a less toxic and more effective substitute for conventional anthracyclines in both newly diagnosed and refractory/recurrent pediatric cancers. Most pediatric cancers are highly chemo-sensitive, and cytotoxic chemotherapy has always been the mainstay of treatment. Anthracyclines are highly effective against most types of childhood cancer, such as neuroblastoma, hepatoblastoma, nephroblastoma, rhabdomyosarcoma, Ewing sarcoma, and so forth. However, acute and chronic cardiotoxicity, one of the major disadvantages of anthracycline use, limits their utility and effectiveness. Hydroxypropyl acrylamide polymer-conjugated pirarubicin (P-THP), which targets tumor tissue highly selectively via the enhanced permeability and retention (EPR) effect, and secondarily releases active pirarubicin molecules quickly into the acidic environment surrounding the tumor. Although, the latter rarely occurs in the non-acidic environment surrounding normal tissue. This mechanism has the potential to minimize acute and chronic toxicities, including cardiotoxicity, as well as maximize the efficacy of chemotherapy through synergy with tumor-targeting accumulation of the active molecules and possible dose-escalation. Simply replacing doxorubicin with P-THP in a given regimen can improve outcomes in anthracycline-sensitive pediatric cancers with little risk of adverse effects, such as cardiotoxicity. As cancer is a dynamic disease showing intra-tumoral heterogeneity during its course, continued parallel development of cytotoxic agents and molecular targeting agents is necessary to find potentially more effective treatments.
登录
查看更多内容
影响因子：
10.8
作者：
Germain, Matthieu;Caputo, Fanny;Schmid, Ruth
通讯作者：
Schmid, Ruth
影响因子：
45.3
作者：
Getz, Kelly D.;Sung, Lillian;Aplenc, Richard
通讯作者：
Aplenc, Richard
影响因子：
5.4
作者：
Kudláčová J;Kotrchová L;Kostka L;Randárová E;Filipová M;Janoušková O;Fang J;Etrych T
通讯作者：
Etrych T
影响因子：
--
作者：
Gu, Xi;Jia, Shi;Zhang, Wen-Hai
通讯作者：
Zhang, Wen-Hai
影响因子：
45.3
作者：
Granowetter, Linda;Womer, Richard;Grier, Holcombe E.
通讯作者：
Grier, Holcombe E.