Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas 66506, United States.
National Wildlife Research Center, USDA APHIS WS, Fort Collins, Colorado 80521, United States.
Mol Pharm. 2024 Feb 5;21(2):970-981. doi: 10.1021/acs.molpharmaceut.3c01080. Epub 2024 Jan 11.
Biodistribution tracks compounds or molecules of interest in vivo to understand a compound's anticipated efficacy and safety. Nanoparticles deliver nucleic acid and drug payloads and enhance tumor permeability due to multiple properties such as high surface area to volume ratio, surface functionalization, and modifications. Studying the in vivo biodistribution of nanoparticles documents the effectiveness and safety of nanoparticles and facilitates a more application-driven approach for nanoparticle development that allows for more successful translation into clinical use. In this study, we present a relatively simple method to determine the biodistribution of magnetic iron nanoparticles in mice. In vitro, cells take up branched amphiphilic peptide-coated magnetic nanobeads (BAPc-MNBs) like their counterparts, i.e., branched amphiphilic peptide capsules (BAPCs) with a hollow water-filled core. Both BAPc-MNBs and BAPCs have widespread applications as a nanodelivery system. We evaluated the BAPc-MNBs tissue distribution in wild-type mice injected intravenously (i.v.), intraperitoneally (i.p.), or orally gavaged to understand the biological interactions and to further the development of branched amphiphilic peptide-based nanoparticles. The magnetic nanoparticles allowed collection of the BAPc-MNBs from multiple organs by magnetic bead sorting, followed by a high-throughput screening for iron content. When injected i.v., nanoparticles were distributed widely to various organs before elimination from the system via the intestines in feces. The spleen accumulated the highest amount of BAPc-MNBs in mice administered NPs via i.v. and i.p. but not via oral gavage. Taken together, these data demonstrate that the magnetic sorting not only allowed quantification of the BAPc-MNBs but also identified the distribution of BAPc-MNBs after distinct administration methods.
生物分布追踪体内感兴趣的化合物或分子,以了解化合物的预期疗效和安全性。纳米粒子通过多种特性(如高表面积与体积比、表面功能化和修饰)来递送核酸和药物有效载荷,并增强肿瘤通透性。研究纳米粒子的体内生物分布可记录纳米粒子的有效性和安全性,并促进更具应用驱动的纳米粒子开发方法,从而更成功地将其转化为临床应用。在这项研究中,我们提出了一种相对简单的方法来确定小鼠体内磁性铁纳米粒子的生物分布。在体外,细胞摄取支链两亲肽包覆的磁性纳米珠(BAPc-MNBs),就像它们的对应物,即具有空心水填充核的支链两亲肽胶囊(BAPCs)一样。BAPc-MNBs 和 BAPCs 都广泛用作纳米递药系统。我们评估了静脉内(i.v.)、腹膜内(i.p.)或口服注射到野生型小鼠体内的 BAPc-MNBs 的组织分布,以了解生物相互作用,并进一步开发基于支链两亲肽的纳米粒子。磁性纳米粒子允许通过磁珠分选从多个器官中收集 BAPc-MNBs,然后进行高通量筛选以检测铁含量。当静脉内注射时,纳米粒子广泛分布于各种器官,然后通过肠道从系统中以粪便形式排出。与通过 i.v. 和 i.p. 给药相比,通过口服给予 NPs 的小鼠脾脏中积累了最高量的 BAPc-MNBs。总之,这些数据表明,磁性分选不仅允许定量 BAPc-MNBs,还可以确定不同给药方法后 BAPc-MNBs 的分布。
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