Smart IR780 Theranostic Nanocarrier for Tumor-Specific Therapy: Hyperthermia-Mediated Bubble-Generating and Folate-Targeted Liposomes
Smart IR780 Theranostic Nanocarrier for Tumor-Specific Therapy: Hyperthermia-Mediated Bubble-Generating and Folate-Targeted Liposomes
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DOI：
10.1021/acsami.5b06552
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发表时间：
2015-09-23
影响因子：
9.5
通讯作者：
Li, Nan
中科院分区：
文献类型：
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作者：
Guo, Fang;Yu, Meng;Li, Nan
化疗的治疗效果受到剂量限制性毒性的阻碍，并且只有当肿瘤细胞受到最大药物暴露时才是最佳的。本研究旨在设计一种结合靶向配体（叶酸）和光热剂（IR 780）的双功能温敏性泡状脂质体（BTSL），以实现增强的治疗和诊断功能。该药物载体被提议由于FA特异性结合而靶向肿瘤细胞，随后由于通过经受近红外（近IR）激光照射分解封装的碳酸氢铵（NH 4 HCO 3）（产生CO2气泡）而触发药物释放，从而在脂质双层中产生可渗透缺陷，从而快速释放药物。体外温度触发释药研究表明，BTSL系统对热触发敏感，导致在高温下快速释药。对于体外细胞摄取实验，在人表皮样癌细胞（KB细胞）和人肺癌细胞（A549细胞）上观察到不同的结果，这是由于它们对FA受体的不同（阳性或阴性）反应。体内生物分布和抗肿瘤研究表明，IR 780-BTSL-FA能特异性靶向KB肿瘤细胞，循环时间较游离药物延长。在药效学实验中，IR 780-BTSL-FA能有效抑制裸鼠肿瘤生长，对正常组织器官无明显毒副作用。本研究结果表明，构建的智能治疗统计纳米载体IR 780-BTSL-FA可能有助于建立肿瘤选择性和有效的化疗。
The therapeutic effectiveness of chemotherapy was hampered by dose-limiting toxicity and was optimal only when tumor cells were subjected to a maximum drug exposure. The purpose of this work was to design a dual-functional thermosensitive bubble-generating liposome (BTSL) combined with conjugated targeted ligand (folate, FA) and photothermal agent (IR780), to realize enhanced therapeutic and diagnostic functions. This drug carrier was proposed to target tumor cells owing to FA-specific binding, followed by triggering drug release due to the decomposition of encapsulated ammonium bicarbonate (NH4HCO3) (generated CO2 bubbles) by being subjected to near-infrared (near-IR) laser irradiation, creating permeable defects in the lipid bilayer that rapidly release drug. In vitro temperature-triggered release study indicated the BTSL system was sensitive to heat triggering, resulting in rapid drug release under hyperthermia. For in vitro cellular uptake experiments, different results were observed on human epidermoid carcinoma cells (KB cells) and human lung cancer cells (A549 cells) due to their different (positive or negative) response to FA receptor. Furthermore, in vivo biodistribution analysis and antitumor study indicated IR780-BTSL-FA could specifically target KB tumor cells, exhibiting longer circulation time than free drug. In the pharmacodynamics experiments, IR780-BTSL-FA efficiently inhibited tumor growth in nude mice with no evident side effect to normal tissues and organs. Results of this study demonstrated that the constructed smart theranosttic nanocarrier IR780-BTSL-FA might contribute to establishment of tumor-selective and effective chemotherapy.