Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5157590 | Carbohydrate Polymers | 2017 | 33 Pages |
Abstract
In this study, we developed bio-stimuli-responsive multi-scale hyaluronic acid (HA) nanoparticles encapsulated with polyamidoamine (PAMAM) dendrimers as the subunits. These HA/PAMAM nanoparticles of large scale (197.10 ± 3.00 nm) were stable during systematic circulation then enriched at the tumor sites; however, they were prone to be degraded by the high expressed hyaluronidase (HAase) to release inner PAMAM dendrimers and regained a small scale (5.77 ± 0.25 nm) with positive charge. After employing tumor spheroids penetration assay on A549 3D tumor spheroids for 8 h, the fluorescein isothiocyanate (FITC) labeled multi-scale HA/PAMAM-FITC nanoparticles could penetrate deeply into these tumor spheroids with the degradation of HAase. Moreover, small animal imaging technology in male nude mice bearing H22 tumor showed HA/PAMAM-FITC nanoparticles possess higher prolonged systematic circulation compared with both PAMAM-FITC nanoparticles and free FITC. In addition, after intravenous administration in mice bearing H22 tumors, methotrexate (MTX) loaded multi-scale HA/PAMAM-MTX nanoparticles exhibited a 2.68-fold greater antitumor activity.
Keywords
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Organic Chemistry
Authors
Mengmeng Huo, Wenyan Li, Arka Sen Chaudhuri, Yuchao Fan, Xiu Han, Chen Yang, Zhenghong Wu, Xiaole Qi,