Targeted delivery of anticancer drugs with intravenously administered magnetic liposomes in osteosarcoma-bearing hamsters.
Targeted delivery of anticancer drugs with intravenously administered magnetic liposomes in osteosarcoma-bearing hamsters.
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DOI：
10.3892/ijo.17.2.309
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发表时间：
2000-08
影响因子：
5.2
通讯作者：
T. Kubo;Takashi Sugita;S. Shimose;Yasuaki Nitta;Yoshikazu Ikuta;T. Murakami
中科院分区：
文献类型：
--
作者：
T. Kubo;Takashi Sugita;S. Shimose;Yasuaki Nitta;Yoshikazu Ikuta;T. Murakami
虽然利用磁性响应载体主动靶向抗癌药物是治疗实体肿瘤的一种非常有吸引力的方法，但成功的结果有限。特别是，静脉注射磁性响应性载体的治疗作用迄今尚未明确确定。本研究旨在研究磁性脂质体作为抗癌药物载体，可以通过静脉给药有效地输送到实体肿瘤。采用反相蒸发法制备了阿霉素磁性脂质体(ADR磁性脂质体)，并进行了体内磁靶向实验。制备的脂质体平均粒径为146 nm。叙利亚雄性金黄地鼠右后肢接种骨肉瘤(Os515)，接种后7天进行研究。给仓鼠静脉注射磁性ADR脂质体或ADR溶液(相当于5mgADR/kg)后，在指定的时间间隔测定ADR在血浆、肿瘤、肝脏、肺、心脏和肾脏的浓度。使用植入实体肿瘤的永磁体(0.4特斯拉)在磁力作用下给药的磁性ADR脂质体在肿瘤中的最大ADR浓度比给药ADR溶液高约4倍。与后者相比，前一种给药方式引起肝脏和肺中ADR浓度的增加和心脏中ADR浓度的下降。结果表明，静脉注射磁性ADR脂质体可以有效地将ADR输送到植入磁铁的骨肉瘤以及骨肉瘤常见的转移部位--肺。我们的结果还表明，这种新的治疗方法，包括靶点磁铁植入和静脉注射磁性脂质体，可以提高实体瘤的临床化疗效果。
Although active targeting of anticancer drugs using magnetically responsive carriers is a very attractive treatment approach for solid tumors, successful results are limited. In particular, the therapeutic utility of intravenously administered magnetically responsive carriers has to date not been clearly established. The present study investigates magnetic liposomes designed to act as anticancer drug carriers, which can be effectively delivered to solid tumors via intravenous administration. Magnetic liposomes with incorporated adriamycin (magnetic ADR liposomes) were prepared by the reverse-phase evaporation method, and an in vivo study was carried out to assess the magnetic targeting of these liposomes to hamster osteosarcoma. The average diameter of liposomes thus prepared was 146 nm. Syrian male hamsters inoculated with osteosarcoma, Os515, in the right hind limb were studied 7 days after inoculation. After the hamsters had received an intravenous administration of either magnetic ADR liposomes or ADR solution (corresponding to 5 mg ADR/kg), the ADR concentrations in plasma, tumor, liver, lung, heart, and kidney were determined at designated time intervals. Administration of magnetic ADR liposomes under magnetic force using a permanent magnet (0.4 tesla) implanted in solid tumor produced an approximately 4-fold higher maximum ADR concentration in the tumor than did administration of ADR solution. The former administration modality induced an increase in ADR concentration in the liver and lung and a decrease in the heart compared with concentrations produced by the latter. The present results indicated that intravenously administered magnetic ADR liposomes can be used to effectively deliver ADR to osteosarcoma implanted with a magnet, as well as to the lung, a common site of metastases for osteosarcoma. Our results also suggest that this new treatment approach, which involves a combination of magnet implantation at the target site and intravenous administration of magnetic liposomes, can improve the clinical chemotherapy of solid tumors.