Radionuclides transform chemotherapeutics into phototherapeutics for precise treatment of disseminated cancer.
Radionuclides transform chemotherapeutics into phototherapeutics for precise treatment of disseminated cancer.
复制标题
放射性核素将化学治疗剂转化为光疗法，以精确治疗传播癌症。
DOI：
10.1038/s41467-017-02758-9
复制
发表时间：
2018-01-18
影响因子：
16.6
通讯作者：
Achilefu S
中科院分区：
文献类型：
--
作者：
Kotagiri N;Cooper ML;Rettig M;Egbulefu C;Prior J;Cui G;Karmakar P;Zhou M;Yang X;Sudlow G;Marsala L;Chanswangphuwana C;Lu L;Habimana-Griffin L;Shokeen M;Xu X;Weilbaecher K;Tomasson M;Lanza G;DiPersio JF;Achilefu S
大多数癌症患者死于播散性疾病，因为传统的全身治疗缺乏对其体内毒性作用的时空控制，特别是在复杂的环境中，如祖干细胞所在的骨髓中。在这里，我们展示了使用放射性药物的光活化药物治疗播散性癌症。在弥散性多发性骨髓瘤细胞中，正交靶向策略和接触促进纳米胶束技术实现了二茂钛和放射性标记的氟脱氧葡萄糖的高选择性递送和共定位。对癌细胞的选择性消融对驻留的干细胞没有明显的脱靶毒性。基因组学、蛋白质组学和多模态成像分析显示，CD49d（纳米胶束的二聚体蛋白靶点之一）的下调导致了小簇癌细胞的治疗耐药。使用人血清白蛋白-二茂钛制剂对高度转移性乳腺癌模型进行类似治疗，可显著抑制肿瘤生长。这一策略扩大了光疗治疗以前无法治疗的转移性疾病的应用。大多数系统性癌症治疗缺乏时空控制。在这里，作者展示了放射性药物在播散性癌细胞中靶向激活一种光敏药物，作为转移性疾病的潜在体内治疗方法，降低了脱靶毒性。
Most cancer patients succumb to disseminated disease because conventional systemic therapies lack spatiotemporal control of their toxic effects in vivo, particularly in a complicated milieu such as bone marrow where progenitor stem cells reside. Here, we demonstrate the treatment of disseminated cancer by photoactivatable drugs using radiopharmaceuticals. An orthogonal-targeting strategy and a contact-facilitated nanomicelle technology enabled highly selective delivery and co-localization of titanocene and radiolabelled fluorodeoxyglucose in disseminated multiple myeloma cells. Selective ablation of the cancer cells was achieved without significant off-target toxicity to the resident stem cells. Genomic, proteomic and multimodal imaging analyses revealed that the downregulation of CD49d, one of the dimeric protein targets of the nanomicelles, caused therapy resistance in small clusters of cancer cells. Similar treatment of a highly metastatic breast cancer model using human serum albumin-titanocene formulation significantly inhibited cancer growth. This strategy expands the use of phototherapy for treating previously inaccessible metastatic disease. Most of the systemic cancer therapies lack spatiotemporal control. Here, the authors show targeted activation of a light-sensitive drug by radiopharmaceuticals in disseminated cancer cells as potential in vivo treatment of metastatic diseases with reduced off-target toxicity.
登录
查看更多内容
影响因子：
10.8
作者：
Kim, Jiyoung;Santos, Olavo Amorim;Park, Ji-Ho
通讯作者：
Park, Ji-Ho
影响因子：
5
作者：
Bredella, MA;Steinbach, L;Hawkins, R
通讯作者：
Hawkins, R
影响因子：
0.3
作者：
Kroger, N;Kleeberg, UR;Hossfeld, DK
通讯作者：
Hossfeld, DK
影响因子：
78.8
作者：
Pantel, Klaus;Alix-Panabieres, Catherine;Riethdorf, Sabine
通讯作者：
Riethdorf, Sabine
使用负载 Chlorin e6 的中空介孔二氧化硅纳米颗粒进行切伦科夫辐射诱导光动力疗法。
影响因子：
9.5
作者：
Kamkaew, Anyanee;Cheng, Liang;Goel, Shreya;Valdovinos, Hector F.;Barnhart, Todd E.;Liu, Zhuang;Cai, Weibo
通讯作者：
Cai, Weibo