Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 32, Issue 36, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202204666
Keywords
beta-glucan; Dectin-1; microfluidics; myocardial reperfusions; NLRP3 inflammasomes
Categories
Funding
- National Key RD Program
- National Natural Science Foundation of China [2017YFA0504504, 22025702, 91853203, 82021003]
- Fundamental Research Funds for the Central Universities of China [20720190101, 20720200008]
- Program of Introducing Talents of Discipline to Universities [B06016]
- National Science Foundation for Distinguished Young Scholar of China [8212500418]
- Academy of Finland [317042, 340129, 331151]
- Orion Research Foundation
- Sigrid Juselius Foundation
- UMCG Research Funds
- Magnus Ehrnrooth Foundation
- Olvi Foundation [2020032]
- Vare children cancer Foundation
- Finnish-Norwegian medical Foundation
- Tor, joe and Pentti Borg Foundation
- Ida Montin Foundation
- Waldemar Von Frenckell Foundation
- Biorender in art design
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This study presents a method for preparing ligand-free targeted nanoparticles (NPs) for the heart, and demonstrates their potential for improving cardiac ischemic/reperfusion (I/R) injury.
Nanoparticle (NP)-based intravenous administration represents the most convenient cardiac targeting delivery routine, yet, there are still therapeutic issues due to the lack of targeting efficiency and specificity. Active targeting methods using functionalization of ligands onto the NPs' surface may be limited by trivial modification procedures and reduced targeting yield in vivo. Here, a microfluidics assisted single step, green synthesis method is introduced for producing targeting ligands free heart homing NPs in a tailored manner. The generated beta-glucan-based NPs exhibit precise and efficient targeting capability toward Dectin-1(+) monocytes/macrophages, which are confirmed as main pathogenesis mediators for cardiac ischemic/reperfusion (I/R) injury, with a sequentially enhanced cardiac NP accumulation, and this targeting strategy is exclusively suitable for cardiac I/R but not for other cardiovascular diseases, as confirmed both in murine and human model. Comparing to FDA-approved nano-micelles formulation, beta-glucan NPs loaded with NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome inhibitor (CY-09) exhibit better efficiency in ameliorating myocardial injury and heart failure induced by surgically induced I/R. These findings indicate a simple production of targeting-ligand free NPs, and demonstrate their potential therapeutic applications for preclinical I/R-induced cardiac injury amelioration.
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