School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, PR China.
State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, Shandong Province, PR China; School of Pharmacy, Binzhou Medical University, Yantai, PR China.
J Control Release. 2016 Jun 28;232:161-74. doi: 10.1016/j.jconrel.2016.04.015. Epub 2016 Apr 14.
Dendrosomes are new tumor targeted drug delivery systems to improve safety and therapeutic effects of antitumor agents. In this study we designed and synthesized magnetically and pH dual responsive dendrosomes with magnetic nanoparticles and folate-targeted dendrimers encapsulated in long-circulating pH sensitive liposomes. Cellular uptake and tissue penetration were assessed on cell lines and tumor spheroids respectively. Xenograft mice were used to study tumor accumulation. The dendrosomes were stable at pH7.4, but responsively released their content at acidic pH. In slightly acid environments, the hybrid vectors showed similar cytotoxicity and cellular uptake to the free folate-dendrimers conjugate due to rapid release. The dendrosomes showed a greater cellular uptake by HeLa cells (FA receptor positive) due to the conjugation with folic acid (FA). In multicellular tumor spheroid tests, a slightly acidic environment and the application of magnet both promoted the permeation efficiency of the hybrid vectors. In the xenograft mice model both in vivo images and tissue distribution assessment indicated that the dendrosomes had higher peak intensity and a longer residence time. Through the synergistic effects of magnetic responsiveness and both passive and active targeting properties, the multi-functional dendrosomes were demonstrated to have great potential as a promising anticancer drug delivery platform.
树突状囊泡是一种新的肿瘤靶向药物传递系统，旨在提高抗肿瘤药物的安全性和治疗效果。在这项研究中，我们设计并合成了具有磁响应和 pH 响应的树突状囊泡，其中包封了磁性纳米颗粒和叶酸靶向树枝状大分子于长循环 pH 敏感脂质体中。分别在细胞系和肿瘤球体上评估了细胞摄取和组织穿透能力。利用异种移植小鼠研究了肿瘤积累。树突状囊泡在 pH7.4 下稳定，但在酸性 pH 下会响应性地释放其内容物。在略酸性环境下，由于快速释放，杂交载体与游离叶酸-树枝状大分子缀合物表现出相似的细胞毒性和细胞摄取。由于与叶酸（FA）的缀合，树突状囊泡对 HeLa 细胞（FA 受体阳性）具有更高的细胞摄取率。在多细胞肿瘤球体试验中，略酸性环境和磁场的应用均促进了杂交载体的渗透效率。在异种移植小鼠模型中，体内成像和组织分布评估均表明，树突状囊泡具有更高的峰值强度和更长的滞留时间。通过磁响应性以及被动和主动靶向特性的协同作用，多功能树突状囊泡具有作为有前途的抗癌药物传递平台的巨大潜力。
