Wang Yifeng, Wang Jine, Yang Yang, Sun Yi, Yuan Yuan, Li Yulin, Liu Changsheng
The State Key Laboratory of Bioreactor Engineering and Key Laboratory for Ultrafine Materials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China.
The State Key Laboratory of Bioreactor Engineering and Key Laboratory for Ultrafine Materials of Ministry of Education, Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China; Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China.
Colloids Surf B Biointerfaces. 2017 May 1;153:272-279. doi: 10.1016/j.colsurfb.2017.02.033. Epub 2017 Feb 27.
Although layer-by-layer assembly using anionic and cationic polymer has been a popular way to develop core-shell nanoparticles, the strong electrostatic interactions may limit shell degradability, thus hampering their application as a platform for controlled therapeutic delivery. In this study, we demonstrate a simple approach to developing mesoporous nanohybrids via a process of pre-drug loading (using doxorubicin (DOX) as a model drug) into mesoporous silica nanoparticles (MSN), followed by surface functionalization with a kind of cationic oligomer (low molecular weight polyethylene imine, LPEI) and in situ crosslinking by degradable N,N'-bis(acryloyl)cystamine (BAC). The presence of LPEI shell affords the nanohybrids with charge-reversal ability, which means that the acidic tumor extracellular microenvironment can transform the negative surface charge at neutral conditions into positive-charged ones. The nanohybrids displayed a pH- and redox-dual sensitivity in DOX release under conditions that mimic intracellular reductive conditions and acidic tumor microenvironments. The nanohybrids can be effectively internalized into A549 cells (a carcinomic human alveolar basal epithelial cell line), resulting in a high DOX intracellular accumulation and an improved anticancer cytotoxicity when compared with free DOX, suggesting their high potential as a new platform for therapeutic delivery.
尽管使用阴离子和阳离子聚合物进行层层组装一直是开发核壳纳米颗粒的常用方法，但强烈的静电相互作用可能会限制壳的降解性，从而阻碍它们作为可控治疗递送平台的应用。在本研究中，我们展示了一种开发介孔纳米杂化物的简单方法，该方法通过将前药（使用阿霉素（DOX）作为模型药物）负载到介孔二氧化硅纳米颗粒（MSN）中，随后用一种阳离子低聚物（低分子量聚乙烯亚胺，LPEI）进行表面功能化，并通过可降解的N,N'-双（丙烯酰基）胱胺（BAC）进行原位交联。LPEI壳的存在赋予纳米杂化物电荷反转能力，这意味着酸性肿瘤细胞外微环境可以将中性条件下的负表面电荷转变为正电荷。在模拟细胞内还原条件和酸性肿瘤微环境的条件下，纳米杂化物在阿霉素释放方面表现出pH和氧化还原双重敏感性。纳米杂化物可以有效地内化到A549细胞（一种人肺泡基底上皮癌细胞系）中，与游离阿霉素相比，导致细胞内阿霉素的高积累和抗癌细胞毒性的提高，表明它们作为治疗递送新平台具有很高的潜力。
