Thermo and pH Dual‐Responsive Nanoparticles for Anti‐Cancer Drug Delivery
Thermo and pH Dual‐Responsive Nanoparticles for Anti‐Cancer Drug Delivery
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DOI：
10.1002/adma.200601817
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发表时间：
2007-10
影响因子：
29.4
通讯作者：
Leyang Zhang;Rui Guo;Mi Yang;Xiqun Jiang;Baorui Liu
中科院分区：
文献类型：
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作者：
Leyang Zhang;Rui Guo;Mi Yang;Xiqun Jiang;Baorui Liu
刺激响应性药物载体的出现为新一代比传统药物更智能、更有效的抗癌药物传递系统打开了大门。[1-6]某些恶性肿瘤可同时在肿瘤部位周围引起两种刺激。一种是局部温度轻微升高[7]，另一种是细胞外pH值轻微降低（6.8-7.2）。[8]因此，适当设计的对温度和pH双重响应的纳米载体可能能够智能地区分正常组织和病理组织，从而实现更好的靶向效率和治疗效果。事实上，制备双重响应药物载体的努力已经进行了一段时间。Kim的小组在温度和pH双重响应聚合物递送系统上做了一些开创性的工作，用于胰岛素的靶向口服递送。[9]近年来，双响应系统正逐渐扩展到抗癌药物的输送。例如，Soppimath等人制备了由三聚体P（N -异丙基丙烯酰胺-共- N，N -二甲基芳基酰胺-共-10-十一碳烯酸）（P（NIPAAm-共-DMAAm-共-UA））制成的pH触发的热响应纳米颗粒。[2]他们发现，弱酸性环境（pH6.6）可以在体温下引起纳米颗粒聚集，并引发负载抗癌药物阿霉素（DOX）的释放。不幸的是，载药量相当低（2.7%），这限制了它们的实际用途。Kang等人基于NIPAAm、DMAAm和pH敏感性调聚物磺胺甲氧哒嗪的共聚物制造了负载DOX的热和pH响应性纳米颗粒。[三
The emergence of stimuli-responsive drug carriers has opened the door to a new generation of anti-cancer drug delivery systems that are more intelligent and more effective than those conventional ones. [1–6] Certain malignancies can cause two stimuli around tumor site at the same time. One is a slight local temperature increase [7] and the other is a minor decrease in extracellular pH (6.8–7.2). [8] Thus, properly designed nanocarriers that are dual-responsive to both temperature and pH may be able to intelligently distinguish between normal and pathological tissues, achieving better targeting efficiency and treatment efficacy. Indeed, efforts for the preparation of dual-responsive drug carriers have been made for some time. Kim’s group did some pioneering work on the temperature and pH dual-responsive polymeric delivery system for targeted oral delivery of insulin. [9] Recently, dual-responsive systems are gradually being extended to anti-cancer drug delivery. For example, Soppimath et al. prepared pH-triggered thermo responsive nanoparticles made of terpo-lymer P( N -isopropylacrylamide- co - N , N -dimethylarylamide- co -10-undecenoic acid) (P(NIPAAm-co -DMAAm- co -UA)). [2] They found that weak acidic environment (pH6.6) could cause nanoparticle aggregation at body temperature and trigger the release of the loaded anti-cancer drug doxorubicin (DOX). Unfortunately, the drug loading capacity was quite low (2.7%), which limits their practical usefulness. Kang et al. fabricated DOX-loaded thermo and pH responsive nanoparticles based on copolymers of NIPAAm, DMAAm and a pH sensitive telomer sulfamethoxypyridazine. [3