Citation: Zhi Li, Wenpei Li, Shaoping Jiang, Chuan Hu, Yuanyu Huang, Maxim Shevtsov, Huile Gao, Shaobo Ruan. Legumain-triggered aggregable gold nanoparticles for enhanced intratumoral retention[J]. Chinese Chemical Letters, ;2024, 35(7): 109150. doi: 10.1016/j.cclet.2023.109150 shu

Legumain-triggered aggregable gold nanoparticles for enhanced intratumoral retention

Zhi Li ^a ,
Wenpei Li ^a ,
Shaoping Jiang ^a ,
Chuan Hu ^b ,
Yuanyu Huang ^a ,
Maxim Shevtsov ^c ,
Huile Gao ^{b, *,} ,
Shaobo Ruan ^{a, *,}

a.
Advanced Research Institute of Multidisciplinary Sciences, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
b.
Key Laboratory of Drug Targeting and Drug Delivery System, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
c.
Institute of Cytology of Russian Academy of Sciences (RAS), St. Petersburg 194064, Russia

gaohuile@scu.edu.cn

ruanshaobo@bit.edu.cn

Received Date: 24 July 2023
Revised Date: 22 September 2023
Accepted Date: 24 September 2023
Available Online: 26 September 2023

Figures(4)

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.
- Legumain,
- Size-tunable,
- Enhanced retention,
- Stimulus-responsive,
- Nanomedicine
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