Ding Yang, Zhai Kang, Pei Pei, Lin Yue, Ma Yinchu, Zhu Huixia, Shao Mingfeng, Yang Xianzhu, Tao Wei
School of Biological and Medical Engineering, Hefei University of Technology, Hefei 230009, PR China.
Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230026, PR China.
J Colloid Interface Sci. 2017 May 1;493:181-189. doi: 10.1016/j.jcis.2017.01.032. Epub 2017 Jan 11.
Exchange of the chloride ion (Cl) ligands of cisplatin with carboxylates is widely used in fabricating cisplatin loaded nanoparticles for improved cancer therapy. However, the dynamic exchange may cause premature cisplatin release and even disintegration of the nanoparticles in Cl-containing medium such as in plasma. Molecules bearing carboxylates are capable of mediating the mineralization process of calcium phosphate; therefore, it is possible to overcome the disadvantage by sequestering cisplatin in a calcium phosphate nanoparticle (CPNP).
With the hypothesis, precipitation reaction of calcium nitrate and disodium hydrogen phosphate was performed in a solution of poly(ethylene glycol)-poly(acrylic acid) block copolymers with their carboxylates partly conjugated with cisplatin. Then, structure, physicochemical properties, and bioactivity of the product were carefully investigated with multiple characterization methods.
It was revealed a pegylated, cisplatin encapsulated CPNP was prepared; and with appropriate mole ratio of cisplatin to carboxylates, the nanoparticle encapsulated cisplatin efficiently (>90%), was stable and almost entirely prevented the cisplatin release in Cl-containing medium at pH 7.4 but released them in an acidic condition, and showed moderately and greatly enhanced cytotoxicities to the lung cancer cell line A549 and its cisplatin resistance form A549R respectively in comparison with the free cisplatin.
顺铂的氯离子（Cl）配体与羧酸盐的交换被广泛用于制备负载顺铂的纳米颗粒以改善癌症治疗。然而，这种动态交换可能会导致顺铂过早释放，甚至在含氯介质（如血浆）中纳米颗粒解体。带有羧酸盐的分子能够介导磷酸钙的矿化过程；因此，有可能通过将顺铂螯合在磷酸钙纳米颗粒（CPNP）中来克服这一缺点。
基于该假设，在聚（乙二醇）-聚（丙烯酸）嵌段共聚物溶液中进行硝酸钙和磷酸氢二钠的沉淀反应，其羧酸盐部分与顺铂共轭。然后，用多种表征方法仔细研究了产物的结构、物理化学性质和生物活性。
结果表明制备了一种聚乙二醇化的、包裹顺铂的CPNP；在顺铂与羧酸盐的摩尔比合适时，纳米颗粒高效地（>90%）包裹顺铂，稳定且在pH 7.4的含氯介质中几乎完全阻止顺铂释放，但在酸性条件下释放顺铂，并且与游离顺铂相比，分别对肺癌细胞系A549及其顺铂耐药形式A549R表现出中度和显著增强的细胞毒性。
