Multifunctional oxygen-enriching nano-theranostics for cancer-specific magnetic resonance imaging and enhanced photodynamic/ photothermal therapy

The combination of photodynamic therapy (PDT) and photothermal therapy (PTT) has attracted much interest in recent years, but non-specific distribution of photosensitizers and intrinsic tumor hypoxic microenvironment have continued to limit its therapeutic efficiency. We herein report a nano-theranostic system, denoted as Ce6-CuS/MSN@PDA@MnO₂-FA NPs, which combines PDT, PTT, magnetic resonance (MR) imaging with hypoxia-relieving and tumor-targeting functionalities. Central to this design is the use of mussel-inspired polydopamine (PDA) coating to encapsulate the chlorin e6 (Ce6) and copper sulfide nanoparticles (CuS NPs) loaded mesoporous silica nanoparticle (MSN) core. The PDA coating not only acts as pH sensitive gatekeeper to prevent the premature release of Ce6 under non-acidic tumor microenvironment (TME), but also facilitates post-functionalization so that hypoxia-relieving MnO₂ nano-sheets and tumor-targeting ligand folic acid-PEG-thiol (FA-PEG-SH) can be decorated on the outer part of the drug system. In vitro and in vivo measurements clearly demonstrated that all these functionalities worked synergistically as expected. The system, having a low dark cytotoxicity, can be effectively internalized by 4T1 cells and decrease the cell viability to 2% upon 660 nm/808 nm laser irradiation. Tumors in 4T1 tumor-bearing mice can almost be completely destroyed in 2 weeks via combined PDT/PTT. Together with the TME-sensitive MR imaging performance demonstrated, Ce6-CuS/MSN@PDA@MnO₂-FA NPs represent a multifunctional prototype which holds great potential to be developed into clinical theranostics.