Matrix Density Engineering of Hydrogel Nanoparticles with Simulation-Guided Synthesis for Tuning Drug Release and Cellular Uptake.
Matrix Density Engineering of Hydrogel Nanoparticles with Simulation-Guided Synthesis for Tuning Drug Release and Cellular Uptake.
复制标题
水凝胶纳米粒子的基质密度工程与模拟引导合成用于调节药物释放和细胞摄取。
DOI：
10.1021/acsomega.7b00590
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发表时间：
2017
期刊：
影响因子：
4.1
通讯作者：
Kopelman,Raoul
中科院分区：
文献类型：
--
作者：
Shirakura,Teppei;Smith,Christof;Hopkins,ThomasJohnJames;KooLee,Yong-Eun;Lazaridis,Filippos;Argyrakis,Panos;Kopelman,Raoul
使用基于纳米颗粒（NP）的抗肿瘤药物载体已经成为一种新兴的策略，用于选择性地将药物递送至肿瘤区域，从而减少与高全身剂量的抗肿瘤药物相关的副作用。精确控制药物负载和释放是至关重要的，以使NP的治疗指数最大化。在这里，我们提出了一种简单的方法，通过改变胺或羧基官能化的水凝胶纳米颗粒的聚合物基质密度，合成具有可调药物释放的纳米颗粒，同时保持其负载能力。我们发现，具有松散基质的NP释放更多的顺铂，速率高达33倍。此外，羧基官能化的NP负载更多的顺铂，并以比胺官能化的NP更快的速率释放它。我们进行了详细的Monte Carlo计算机模拟，阐明了基质密度和药物释放动力学之间的关系。我们发现，作为时间的函数的药物释放的模拟模型和实验结果之间的良好协议。此外，我们比较了胺官能化的NP和羧基官能化的NP之间的细胞摄取，因为NP的更高的细胞摄取导致改善的顺铂递送。胺官能化的NP可以将比羧基官能化的NP多3.5倍的顺铂递送到细胞中。胺官能化的NP和羧基官能化的NP两者的细胞毒性功效显示与顺铂释放曲线的强相关性，并且后者显示与NP基质密度的强相关性。
The use of a nanoparticle (NP)-based antitumor drug carrier has been an emerging strategy for selectively delivering the drugs to the tumor area and, thus, reducing the side effects that are associated with a high systemic dose of antitumor drugs. Precise control of drug loading and release is critical so as to maximize the therapeutic index of the NPs. Here, we propose a simple method of synthesizing NPs with tunable drug release while maintaining their loading ability, by varying the polymer matrix density of amine- or carboxyl-functionalized hydrogel NPs. We find that the NPs with a loose matrix released more cisplatin, with up to a 33 times faster rate. Also, carboxyl-functionalized NPs loaded more cisplatin and released it at a faster rate than amine-functionalized NPs. We performed detailed Monte Carlo computer simulations that elucidate the relation between the matrix density and drug release kinetics. We found good agreement between the simulation model and the experimental results for drug release as a function of time. Also, we compared the cellular uptake between amine-functionalized NPs and carboxyl-functionalized NPs, as a higher cellular uptake of NPs leads to improved cisplatin delivery. The amine-functionalized NPs can deliver 3.5 times more cisplatin into cells than the carboxyl-functionalized NPs. The cytotoxic efficacy of both the amine-functionalized NPs and the carboxyl-functionalized NPs showed a strong correlation with the cisplatin release profile, and the latter showed a strong correlation with the NP matrix density.