Mesopore-Induced Aggregation of Cobalt Protoporphyrin for Photoacoustic Imaging and Antioxidant Protection of Stem Cells

With the ever-accelerating development of functional materials design and fabrication, various nanomaterial-based molecular imaging platforms with improved detectability and functionality have been developed for next-generation cell tracking technologies in the field of stem cell therapy. In this work, a "mesopore-induced aggregation" strategy is developed to endow cobalt protoporphyrin IX (CoPP), one of the important metalloporphyrins, with photoacoustic (PA) imaging capability by loading it into amine-functionalized mesoporous silica nanoparticles (aMSNs). Through intermolecular aggregation in mesopores, the light absorption of CoPP can be broaden into near-infrared region, resulting in about 7.4-fold enhancement of PA response at 680 nm compared to free CoPP. Moreover, the newly designed PA contrast agent is not only safe for stem cell tracking, but also exerts sustained CoPP release for a long-term cytoprotective effect against oxidative stress. The translational potential of CoPP-loaded MSNs as a theranostic agent is demonstrated via in vivo imaging of the labeled stem cell in nude mice based on subcutaneous- and myocardial-injection approaches. This is the first demonstration of a multifunctional nanoplatform with both PA imaging-guided cell delivery and antioxidant stress cell protection functions, which provides a robust theranostic approach for future stem cell therapy.