Photothermal/ Photodynamic therapy (PTT/ PDT), a viable therapeutic substitute for conventional radiation and chemotherapy, is acknowledged as a tumor-specific treatment paradigm with less therapeutic resistance compared to other approaches. This study demonstrates a unique multifunctional property-enriched nanostructured system that combines counter-folic acid (FA) and the fluorescent dye indocyanine green (ICG) with manganese-doped gold-loaded hydroxyapatite (Au-Mn-HAp). The synthesized Au-Mn-HAp nanoparticles, which are formed like nanorods, enable conjugation of FA/ICG dye with improved in vivo circulation retention time. The drug free Photothermal Photodynamic therapy mediated cancer treatment prevents collateral damages to non-cancerous cells. The doped Mn enables the release of Mn2+ ions which triggered the generation of toxic hydroxyl radicals (-OH) via Fenton or Fenton-like reactions to breakdown H2O2 in the tumor sites. The loaded Au nanoparticle generates hotspots due to plasmonic behavior while irradiated with laser lights. Herein, ICG and FA was selected for targeted fluorescence imaging guided photothermal therapy. HAp performs as a nano-carrier with large surface area to conjugate enhanced FA/ICG on its surface without any toxicity due to its natural biocompatible behavior. The PTT performance of synthesized nanostructured system exhibits improved potential with ~55°C temperature elevation while irradiated at 0.70 W/cm2 laser power. PDT activity was studied with MDA-MB-231 breast cancer cell line, which shows cytotoxicity due to the generated reactive oxygen species (ROS). When administered intravenously (tail vain) in a BALB/c nude mouse model, FA/ICG conjugated Au-Mn-HAp nanoparticles demonstrate significant tumor specific targeting and abalation property without any tumor recurrence. The synthesized nanostructured system was well suited to serve as a promising photo-therapeutic agent for imaging guided cancer treatment.

Near Infrared light-responsive Au loaded Mn doped HAp-based injectable nanoplatform for imaging-guided cancer therapy

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ACS Spring 2023

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