Ultrasmall gold nanosatellite-bearing transformable hybrid nanoparticles for deep tumor penetration

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Title
Ultrasmall gold nanosatellite-bearing transformable hybrid nanoparticles for deep tumor penetration
Author(s)
Soyoung Son; Veerasikku G. Deepagan; Sol Shin; Hyewon Ko; Jiwoong Min; Wooram Um; Jueun Jeon; Seunglee Kwon; Eun Sook Lee; Minal Suh; Doo Sung Lee; Jae Hyung Park
Publication Date
2018-10
Journal
Acta Biomaterialia, v.79, no., pp.294 - 305
Publisher
ELSEVIER SCI LTD
Abstract
Since delivering drugs to an entire tumoral region leads to high therapeutic efficacy and good prognosis, achieving deep tumoral penetration of drugs is a major issue in cancer treatment. In this regard, conventional nanomedicines (>50 nm) have shown limitations in cancer therapy, primarily attributed to the heterogeneous distribution of drugs because of the physiological barrier of the tumor interstitial space. To address this issue, we prepared transformable hybrid nanoparticles (TNPs) consisting of a pHresponsive nanocarrier (PEG-PBAE) and doxorubicin (DOX)-conjugated ultrasmall (<3 nm) gold nanoparticles (nanosatellites). It has been shown that PEG-PBAE can serve as a reservoir for nanosatellites and release them in mildly acidic conditions (pH 6.5), mimicking the tumor microenvironment. When DOXloaded TNPs (DOX-TNPs) were intravenously injected into tumor-bearing mice, they successfully accumulated and dissociated at the extracellular level of the tumor, leading to the disclosure of nanosatellites and free DOX. While the free DOX accumulated in tumor tissue near blood vessels, the deeply diffused nanosatellites were taken up by the tumor cell, followed by the release of DOX via cleavage of pHresponsive ester linkages in the nanosatellites at the intracellular level. Consequently, the DOX-TNPs effectively suppressed tumor growth through improved tumor penetration of DOX, suggesting their promising potential as a cancer nanomedicine. (c)2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
URI
https://pr.ibs.re.kr/handle/8788114/5427
ISSN
1742-7061
Appears in Collections:
Center for Neuroscience Imaging Research (뇌과학 이미징 연구단) > Journal Papers (저널논문)
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