Division of Nanomaterials and Chemistry, Hefei National Laboratory for Physical Sciences at Microscale, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, PR China.
Small. 2010 Nov 5;6(21):2436-42. doi: 10.1002/smll.201000903.
To develop a new system for site-specific targeting, superparamagnetic CaCO(3) mesocrystals with the properties of biocompatibility and biodegradability are designed and synthesized. They serve as carriers for the co-delivery of drug and gene nanoparticles via a multistage method for cancer therapy. With a porous structure, the mesocrystalline CaCO(3) particles encapsulate doxorubicin (DOX), Au-DNA, and Fe(3)O(4)@silica nanoparticles for magnetic control and therapy. As stage 1 microparticles (S1MPs), the nanoparticles-CaCO(3) system is designed to protect functional sections from degradation and phagocytosis in blood circulation. After the particle margination in vascular walls, the Au-DNA nanoparticles (stage 2 nanoparticles, S2NPs) and DOX are gradually released from S1MPs by degradation towards targeted tissues for biomedical therapy. The nanoparticles-CaCO(3) system exhibits high efficiency of intracellular delivery, especially in nuclear invasion. The successful expression of reporter gene and intracellular transport of DOX in vitro suggest potential as a co-delivery system for drug and gene therapy. In a mouse tumor model, the system with particle margination and two-step strategy affords the protection of functional nanoparticles and drug from clearance and inactivation by enzymes and proteins in vivo. The targeted delivery of S2NPs into tumors by this system is tenfold more efficient than that of the nanoparticles themselves. The drug is observed to be widely distributed in tumor slices. Thus, this platform exhibits an efficient approach in the targeted delivery of therapeutic nanoparticles and molecules via a multistage strategy, and can be used as a potential system in co-delivery of multiple agents for biomedical imaging and therapy.
为了开发一种新的靶向定位系统，设计并合成了具有生物相容性和可生物降解性的超顺磁 CaCO(3) 介晶。它们作为药物和基因纳米颗粒共递运载体，通过多阶段方法用于癌症治疗。介晶 CaCO(3) 颗粒具有多孔结构，可包封阿霉素（DOX）、Au-DNA 和 Fe(3)O(4)@硅纳米颗粒，用于磁控制和治疗。作为第一阶段微颗粒（S1MPs），该纳米颗粒-CaCO(3) 系统旨在保护功能部分免受血液循环中降解和吞噬的影响。在粒子在血管壁边缘沉积后，Au-DNA 纳米颗粒（第二阶段纳米颗粒，S2NPs）和 DOX 逐渐从 S1MPs 中通过降解释放到靶向组织，用于生物医学治疗。纳米颗粒-CaCO(3) 系统表现出高效的细胞内递药能力，特别是在核内入侵方面。体外报告基因的成功表达和 DOX 的细胞内转运表明，它具有作为药物和基因共递药系统的潜力。在小鼠肿瘤模型中，具有粒子边缘沉积和两步策略的系统可保护功能纳米颗粒和药物免受体内酶和蛋白质的清除和失活。通过该系统，S2NPs 靶向递送到肿瘤的效率比纳米颗粒本身高十倍。药物在肿瘤切片中广泛分布。因此，该平台通过多阶段策略展示了一种高效的治疗性纳米颗粒和分子靶向递药方法，可作为用于生物医学成像和治疗的多药物共递药的潜在系统。
