体内
纳米医学
阿霉素
化学
体外
细胞内
药物输送
癌症研究
胶体金
纳米颗粒
纳米技术
生物物理学
化疗
材料科学
生物化学
医学
内科学
生物
生物技术
作者
Zhi Li,Wenpei Li,Shaoping Jiang,Chuan Hu,Yuanyu Huang,Maxim Shevtsov,Huile Gao,Shaobo Ruan
标识
DOI:10.1016/j.cclet.2023.109150
摘要
Insufficient intratumoral retention of nanomedicines remains the major challenge for broad implementation in clinical sets. Herein, we proposed a legumain-triggered aggregable gold nanoparticle (GNP) delivery platform (GNPs-A&C). GNPs-A&C could form intratumoral or intracellular aggregates in response to the overexpressed legumain. The aggregates with size increase not only could reduce back-flow from interstitial space to peripheral bloodstream but also could restrict the cellular exocytosis, leading to enhanced intratumoral retention. In vitro studies demonstrated that GNPs-A&C possessed an excellent legumain responsiveness and the increased size was closely relevant with legumain expression. In vivo studies demonstrated GNPs-A&C possessed slower clearance rate and much higher intratumoral retention within legumain-overexpressed tumor compared to non-aggregable NPs, regardless of intravenous or intratumoral injection. More importantly, this delivery platform significantly improved the chemotherapeutic effect of doxorubicin (DOX) towards subcutaneous xenograft C6 tumor. The effectiveness of this stimulus-responsive aggregable delivery system provides a thinking for designing more intelligent size-tunable nanomedicine that can substantially improve intratumoral retention.
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