Near-infrared light triggered in situ release of CO for enhanced therapy of glioblastoma.

BACKGROUND: Photodynamic therapy (PDT) features high biocompatibility and high spatiotemporal selectivity, showing a great potential in glioblastoma (GBM) treatment. However, its application was restricted by the poor therapeutic efficacy and side effect. RESULTS: In this study, a therapeutic nanoplatform (UCNPs@Ce6/3HBQ@CM) with combination of PDT and CO therapy was constructed, in which a photoCORM and a photosensitizer were loaded onto the surface of upconversion nanoparticles (UCNPs) functioning as photon transducer. Benefitting from NIR excitation and multicolor emission of UCNPs, the penetration depth of excitation light is enhanced and meanwhile simultaneous generation of CO and ROS in tumor site can be achieved. The as-prepared nanocomposite possessed an elevated therapeutic efficiency with the assistance of CO through influencing mitochondrial respiration and depleting ATP, accompanying with the reduced inflammatory responses. By wrapping a homologous cell membrane, the nanocomposite can target GBM and accumulate in the tumor site, affording a powerful tool for precise and efficient treatment of GBM. CONCLUSION: This therapeutic nanoplatform UCNPs@Ce6/3HBQ@CM, which combines PDT and CO therapy enables precise and efficient treatment of refractory glioblastoma.

Loading Drugs in Natural Phospholipid Bilayers of Cell Membrane Shells to Construct Biomimetic Nanocomposites for Enhanced Tumor Therapy.

Drug-based oncotherapy is seriously challenged by insufficient drug accumulation at tumor sites, mainly resulting from low drug loading efficiency and poor tumor-targeting ability of drug carriers. We herein proposed a "one-stone, two-bird" strategy to circumvent both obstacles, utilizing the source cancer cell membrane (CM) as a dual-function carrier to simultaneously achieve sufficient drug loading and homologous tumor targeting. Combining the use of TPGS (d-α-tocopherol polyethylene glycol 1000 succinate) to inhibit the drug efflux process of drug-resistant tumor, we constructed core-shell-structured nanocomposites CMGNPs consisting of ICG (indocyanine green)/DOX (doxorubicin)-loaded, TPGS/OA (oleic acid)-stabilized upconversion nanoparticles as the core and ICG-loaded MCF7/ADR CMs as the shell, for combined chemo/phototherapy of MCF7/ADR tumor. The employment of phospholipid bilayers of CMs as natural pockets for extra drug loading while preserving the homologous targeting ability greatly enhanced drug concentration at tumor sites, endowing CMGNPs with excellent therapeutic efficacy. Our effort provides a versatile approach for facilitating drug delivery in diverse therapeutic systems.