期刊
ACS APPLIED MATERIALS & INTERFACES
卷 12, 期 34, 页码 37885-37895出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c10500
关键词
theranostic; mesoporous silica; brain ischemia; cell labeling; stem cell therapy
资金
- National Key R&D Program of China [2019YFA0112000]
- National Natural Science Foundation of China [81601499, 81801170, 81671699]
- Natural Science Foundation of Shanghai [18ZR1444800]
- Shanghai Rising-Star Program [19QA1410300]
- Youth Innovation Promotion Association CAS [2020255]
- Academy of Finland [328933]
The precise transplantation, long-term tracking, and maintenance of stem cells with maximizing therapeutic effect are significant challenges in stem cell-based therapy for stroke treatment. In this study, a unique core-shell labeling nanoagent was prepared by encapsulating a cobalt protoporphyrin IX (CoPP)-loaded mesoporous silica nanoparticle (CPMSN) into a I-125-conjugated/spermine-modified dextran polymer (I-125-SD) by microfluidics for mesenchymal stem cell (MSC) tracking and activity maintenance. The CPMSN core not only exhibits excellent photoacoustic (PA) imaging performance induced by the intermolecular aggregation of CoPP within the mesopores but also protects the MSCs against oxidative stress by sustained release of CoPP. Meanwhile, the addition of a I-125-SD shell can increase the uptake efficiency in MSCs without inducing cell variability and enable the single-photon-emission computed tomography (SPECT) nuclear imaging. In vivo results indicated that CPMSN@I-125-SD labeling could allow for an optimal combination of instant imaging of MSCs, with PA to guide intracerebral injection, followed by multiple time point SPECT imaging to consecutively track the cell homing. Importantly, the sustained release of CoPP from CPMSN@I-125-SD significantly increased the survival of MSCs after injection into an ischemic mouse brain and promoted neurobehavioral recovery in ischemic mice. Thus, CPMSN@I-125-SD represents a robust theranostic probe for both MSC tracking and maintaining their therapeutic effect in the treatment of brain ischemia.
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