Imaging-Guided and Light-Triggered Chemo-/Photodynamic/Photothermal Therapy Based on Gd (III) Chelated Mesoporous Silica Hybrid Spheres

Exploring a combined anticancer therapeutic strategy to overcome the limitations of a single mode and pursue higher therapeutic efficiency is highly promising in both fundamental and clinical investigations. Herein, a theranostic nanoplatform based on mesoporous silica, which is functionalized by hybrid nanosphere photosensitizer Chlorin e6 (Ce6), photothermal agent carbon dots (CDs), and imaging agent Gd (III) ions has been rationally designed and fabricated. A thermo/pH-coupling sensitive polymer (P(NIPAm-co-MAA)) coated on a composite acted as a key “gatekeeper” to control drug release at the appropriate time and location. Upon light irradiation, two-mode synergistic therapeutic effect of photodynamic and photothermal therapy can be achieved by photoactive Ce6 and CDs. Meanwhile, the CDs loaded in the channels of mesoporous silica hybrid spheres can also play a role in handling the “gatekeeper” polymer to control the drug release process. Combined with the thermo/pH-sensitive drug release-induced controllable chemotherapy, this platform shows synergistic therapeutic efficacy better than any single/dual therapy, which is confirmed with evidence from in vivo and in vitro assays. Considering the chelated Gd3+ simultaneously introduced magnetic resonance imaging (MRI) and computed tomography (CT) properties, this multifunctional platform should have excellent potential in the imaging-guided cancer therapy field.