Multiple hyperthermia-mediated release of TRAIL/SPION nanocomplex from thermosensitive polymeric hydrogels for combination cancer therapy

Title
Multiple hyperthermia-mediated release of TRAIL/SPION nanocomplex from thermosensitive polymeric hydrogels for combination cancer therapy
Authors
송수창장지강
Keywords
TRAIL; Controlled release; SPION; Multiple magnetic hyperthermia; Thermosensitive hydrogel
Issue Date
2017-07
Publisher
Biomaterials
Citation
VOL 132-27
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) possesses strong anti-cancer potential because of its ability to specifically kill cancer cells. However, clinical use of TRAIL is impeded by its short in vivo half-life and native TRIAL-resistant cancer cell populations. To overcome these limitations, we designed a multiple magnetic hyperthermia (MHT)-mediated TRAIL release system for combination therapy using an injectable, biodegradable and thermosensitive polymeric hydrogel. In this system, positively charged TRAIL and hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) are complexed with negatively charged poly(organophosphazene) polymers via ionic and hydrophobic interactions, respectively. Transmission electron microscopy images showed a nano-sized core-shell structure of the TRAIL/SPION polymeric nanocomplex in aqueous solution that transformed into a hydrogel at body temperature. Hyperthermia can enhance the release of TRAIL from hydrogels through temperature-sensitive hydrogel dissolution. TRAIL-resistant U-87 MG cells were killed by the combination of TRAIL and multiple hyperthermia via caspase-3 and -8 active apoptosis. The hyperthermia-enhanced cytotoxicity of TRAIL was dependent on the hyperthermia cycle number and corresponding TRAIL release. Significant in vivo tumor reduction was observed by combining 2 cycles of mild MHT and TRAIL release using a single injection of TRAIL/SPION nanocomplex hydrogels without damage to main organs. Furthermore, the therapeutic outcomes can be monitored by long-term magnetic resonance imaging.
URI
https://pubs.kist.re.kr/handle/201004/65817
ISSN
0142-9612
Appears in Collections:
KIST Publication > Article
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