Engineering of SPECT/Photoacoustic Imaging/Antioxidative Stress Triple-Function Nanoprobe for Advanced Mesenchymal Stem Cell Therapy of Cerebral Ischemia

Abstract

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 125 I-conjugated/spermine-modified dextran polymer ( 125 I-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 125 I-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@ 125 I-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@ 125 I-SD significantly increased the survival of MSCs after injection into an ischemic mouse brain and promoted neurobehavioral recovery in ischemic mice. Thus, CPMSN@ 125 I-SD represents a robust theranostic probe for both MSC tracking and maintaining their therapeutic effect in the treatment of brain ischemia.

Progress in Mesenchymal Stem Cell Therapy for Ischemic Stroke

“…Yao et al proposed a new nanoplatform to load MSCs. This method allows us to quantitatively detect cell migration by SPECT imaging after transplantation, and it can continuously release cobalt protoporphyrin IX to protect cells from oxidative stress, thus increasing the survival of MSCs in ischemic lesions [197]. The MCAO model mice transplanted with MSCs through this method showed better neurological recovery [197].…”

Neuroinflammation Treatment via Targeted Delivery of Nanoparticles

“…Preliminary data suggests preferential uptake by microglial cells and safety in vitro. Another recent study proposes the use of theranostic nanoparticles for long-term tracking of transplanted cells coupled with antioxidant treatment following stroke (Yao et al, 2020). Mesoporous core-shellstructured nanoparticles loaded with cobalt protoporphyrin IX and conjugated to 125 I/spermine-modified dextran polymer conferred protection to transplanted mesenchymal stem cells (MSC) from oxidative stress.…”

Nanoparticles for Stem Cell Tracking and the Potential Treatment of Cardiovascular Diseases

“…(C) Single-photon emission computed tomography imaging (SPECT)/CT images of ischemic mouse brain tissue on different days (0-7 days) after intracerebral injection of the labeled BMSCs (500,000 cells). (D) Cell death assessment for MSCs after treatment with different concentrations of CPMSN@125I-SD (0-100 µg ml −1 ) and exposure to 100 µM H 2 O 2 for 24 and 48 h. (E) Bar graph showing the quantification of the number of CD 31+ cells (adapted from Yao et al, 2020). * p < 0.05; * * p < 0.01.…”

“…Furthermore, it has excellent biocompatibility and chemical inertness, thus, being able to serve as a probe for tracking cells in vivo (Huang et al, 2005;Hsiao et al, 2008). Silicon-based NPs, being simply divided into silica NPs and silicon carbide NPs, not only contain fluorescent properties but also are used as ultrasound agents (Chen and Jokerst, 2020;Yao et al, 2020). Huang et al (2005) prepared a mesoporous silica NP modified by fluorescein isothiocyanate, and the labeled MSCs could be detected by imaging to track their viability in vivo.…”