Bio-stimuli-responsive multi-scale hyaluronic acid nanoparticles for deepened tumor penetration and enhanced therapy. (1st September 2017)

• Record Type: Journal Article
• Authors: Huo, Mengmeng; Li, Wenyan; Chaudhuri, Arka Sen; Fan, Yuchao; Han, Xiu; Yang, Chen; Wu, Zhenghong; Qi, Xiaole
• Is Part Of: Carbohydrate polymers. Volume 171(2017)
• Page Start: 173
• Page End: 182
• Publication Date: 2017-09-01
• Subjects: 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (PubChem CID: 2723939) -- Adipicdihydrazide (PubChem CID: 66117) -- Fluorescein isothiocyanate (PubChem CID: 18730) -- Methotrexate (PubChem CID: 126941) -- Sodium hyaluronate (PubChem CID: 3084049); Multi-scale nanoparticles -- Deepened tumor penetration -- PAMAM dendrimers -- Hyaluronic acid -- Hyaluronidase; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2017.05.017
• Languages: English
• ISSNs: 0144-8617

Abstract

Highlights: Multi-scale HA nanoparticles encapsulated with PAMAM dendrimers were developed. The fine bio-stimuli-responsive properties of HA/PAMAM nanoparticles was verified. The in vitro tumor spheroids deeply penetration of HA/PAMAM-FITC was confirmed. HA/PAMAM-FITC showed prolonged systematic circulation in mice bearing H22 tumor. HA/PAMAM-MTX demonstrated higher antitumor activity in H22 sarcoma mice. 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.