In vivo fate tracking of degradable nanoparticles for lung gene transfer using PET and Ĉerenkov imaging.
In vivo fate tracking of degradable nanoparticles for lung gene transfer using PET and Ĉerenkov imaging.
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DOI：
10.1016/j.biomaterials.2016.04.040
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发表时间：
2016-08
期刊：
影响因子：
14
通讯作者：
Brody SL
中科院分区：
文献类型：
--
作者：
Black KC;Ibricevic A;Gunsten SP;Flores JA;Gustafson TP;Raymond JE;Samarajeewa S;Shrestha R;Felder SE;Cai T;Shen Y;Löbs AK;Zhegalova N;Sultan DH;Berezin M;Wooley KL;Liu Y;Brody SL
纳米颗粒在生物医学领域的应用越来越广泛，包括成像和治疗，然而，它们的长期命运和清除特性尚未在体内得到充分表征。经由气道的NP递送是特别具有挑战性的，因为清除可能是低效的并且肺免疫应答复杂。因此，特定的材料设计是必需的货物交付和定量，非侵入性的方法，需要表征NP药代动力学。在这里，生物相容性聚（丙烯酰胺基乙胺）-b-聚（DL-丙交酯）嵌段共聚物为基础的可降解的，阳离子的，壳交联的膝状纳米粒子（Dg-cSCKs）被用来转染质粒DNA。安装了放射性和光学信标，以监测生物分布和成像。与不可降解的对应物相比，在酸性条件下货物的优先释放提供了增强的转染效率。通过放射性标记Dg-cSCKs并使用平行正电子发射断层扫描和Čerenkov成像进行定量生物分布，将体内基因转移至肺与NP药代动力学相关。14天内的成像定量与NP从肺向胃肠道和肾脏途径移动的药代动力学一致，与预测的降解和排泄一致。这种非侵入性和准确跟踪NP命运的能力突出了将多功能性纳入颗粒设计的优势。
Nanoparticles (NPs) play expanding roles in biomedical applications including imaging and therapy, however, their long-term fate and clearance profiles have yet to be fully characterized in vivo. NP delivery via the airway is particularly challenging, as the clearance may be inefficient and lung immune responses complex. Thus, specific material design is required for cargo delivery and quantitative, noninvasive methods are needed to characterize NP pharmacokinetics. Here, biocompatible poly(acrylamidoethylamine)-b-poly(DL-lactide) block copolymer-based degradable, cationic, shell-cross-linked knedel-like NPs (Dg-cSCKs) were employed to transfect plasmid DNA. Radioactive and optical beacons were attached to monitor biodistribution and imaging. The preferential release of cargo in acidic conditions provided enhanced transfection efficiency compared to non-degradable counterparts. In vivo gene transfer to the lung was correlated with NP pharmacokinetics by radiolabeling Dg-cSCKs and performing quantitative biodistribution with parallel positron emission tomography and Čerenkov imaging. Quantitation of imaging over 14 days corresponded with the pharmacokinetics of NP movement from the lung to gastrointestinal and renal routes, consistent with predicted degradation and excretion. This ability to noninvasively and accurately track NP fate highlights the advantage of incorporating multifunctionality into particle design.