In‐vitro and in‐vivo evaluation of pH‐responsive polymeric micelles in a photodynamic cancer therapy model
In‐vitro and in‐vivo evaluation of pH‐responsive polymeric micelles in a photodynamic cancer therapy model
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光动力癌症治疗模型中 pH 响应聚合物胶束的体外和体内评估
DOI：
10.1211/0022357011775352
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发表时间：
2001
影响因子：
3.3
通讯作者：
J. Leroux
中科院分区：
文献类型：
--
作者：
J. Taillefer;N. Brasseur;J. E. Lier;V. Lenaerts;D. Garrec;J. Leroux
制备并表征了无规和末端烷基化N-异丙基丙烯酰胺共聚物的pH敏感聚合物胶束。采用透析法将第二代光动力学抗癌增敏剂氯化铝酞菁（AlClPc）引入胶束中。在体外对EMT-6小鼠乳腺肿瘤细胞和体内对Balb/c小鼠各后腿皮内植入的EMT-6肿瘤评价了其光动力学活性。发现pH敏感性聚合物胶束在体外表现出比对照Cremophor EL制剂更大的细胞毒性。在存在氯喹（一种弱碱，可提高酸性细胞器的内部pH值）的情况下，体外实验证明了内体/溶酶体酸度对于pH敏感性聚合物胶束充分有效的重要性。静脉注射2 μmol kg−1 AlClPc后，通过组织提取物的荧光评估生物分布。结果显示AlClPc聚合物胶束在肝、脾和肺中的积累，具有比AlClPc Cremophor EL制剂更低的肿瘤摄取。然而，聚合物胶束表现出与对照Cremophor EL制剂相似的体内活性，证明了AlClPc聚合物胶束在定位于肿瘤组织中时的更高效力。得出的结论是，聚合物胶束代表了一个很好的替代Cremophor EL制剂的疏水药物的载体化。
pH‐sensitive polymeric micelles of randomly and terminally alkylated N‐isopropylacrylamide copolymers were prepared and characterized. Aluminium chloride phthalocyanine (AlClPc), a second generation sensitizer for the photodynamic therapy of cancer, was incorporated in the micelles by dialysis. Their photodynamic activities were evaluated in‐vitro against EMT‐6 mouse mammary tumour cells and in‐vivo against EMT‐6 tumours implanted intradermally on each hind thigh of Balb/c mice. pH‐sensitive polymeric micelles were found to exhibit greater cytotoxicity in‐vitro than control Cremophor EL formulations. In the presence of chloroquine, a weak base that raises the internal pH of acidic organelles, in‐vitro experiments demonstrated the importance of endosomal/lysosomal acidity for the pH‐sensitive polymeric micelles to be fully effective. Biodistribution was assessed by fluorescence of tissue extracts after intravenous injection of 2 μmol kg−1 AlClPc. The results revealed accumulation of AlClPc polymeric micelles in the liver, spleen and lungs, with a lower tumour uptake than AlClPc Cremophor EL formulations. However, polymeric micelles exhibited similar activity in‐vivo to the control Cremophor EL formulations, demonstrating the higher potency of AlClPc polymeric micelles when localized in tumour tissue. It was concluded that polymeric micelles represent a good alternative to Cremophor EL preparations for the vectorization of hydrophobic drugs.
DOI：
10.1016/0005-2736(89)90453-7
发表时间：
1989-12-11
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
COLLINS, D;MAXFIELD, F;HUANG, L
通讯作者：
HUANG, L