TY - JOUR
T1 - Engineering of SPECT/Photoacoustic Imaging/Antioxidative Stress Triple-Function Nanoprobe for Advanced Mesenchymal Stem Cell Therapy of Cerebral Ischemia
AU - Yao, Minghua
AU - Shi, Xiaojing
AU - Zuo, Changjing
AU - Ma, Ming
AU - Zhang, Lu
AU - Zhang, Hongbo
AU - Li, Xin
AU - Yang, Guo-Yuan
AU - Tang, Yaohui
AU - Wu, Rong
PY - 2020/8/26
Y1 - 2020/8/26
N2 - 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 125I-conjugated/spermine-modified dextran polymer (125I-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 125I-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@125I-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@125I-SD significantly increased the survival of MSCs after injection into an ischemic mouse brain and promoted neurobehavioral recovery in ischemic mice. Thus, CPMSN@125I-SD represents a robust theranostic probe for both MSC tracking and maintaining their therapeutic effect in the treatment of brain ischemia.
AB - 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 125I-conjugated/spermine-modified dextran polymer (125I-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 125I-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@125I-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@125I-SD significantly increased the survival of MSCs after injection into an ischemic mouse brain and promoted neurobehavioral recovery in ischemic mice. Thus, CPMSN@125I-SD represents a robust theranostic probe for both MSC tracking and maintaining their therapeutic effect in the treatment of brain ischemia.
U2 - 10.1021/acsami.0c10500
DO - 10.1021/acsami.0c10500
M3 - Article
VL - 12
SP - 37885
EP - 37895
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
SN - 1944-8244
IS - 34
ER -