Pulmonary Delivery of GSH-responsive 131I-labeled Albumin-Based Nanosystem for Lung Cancer with Enhanced Cerenkov-induced Photodynamic Therapy

Cerenkov radiation-induced photodynamic therapy (CR-PDT) addresses the tissue penetration limitations of traditional photodynamic therapy for deep-seated tumors. However, continuous phototoxicity in normal tissues and inefficient tumor accumulation of co-delivery of radionuclides and photosensitizer remain the main challenges to the therapy efficacy of lung cancer. Here, we developed a novel pulmonary delivered 131 I-labeled GSH-responsive chlorin e6 (Ce6)-conjugated Bovine Serum Albumin (BSA) nanoassembly ( 131 I-CBA ) for efficient and selective tumor therapy in orthotopic lung cancer. The 131 I-CBA, with a stable diameter of around 150 to 200   nm, were designed to show minimal phototoxicity in normal tissues due to the aggregation-caused quenching (ACQ). Under tumor intracellular reductive glutathione (GSH) conditions, the dissociation of nanosystem happened, restoring the quenched photoactivity of Ce6 to produce singlet oxygen. After pulmonary delivery in orthotopic lung cancer, 131 I-CBA showed high lung accumulation and great tumor inhibition capability with excellent biosafety. We believe that this pulmonary delivered 131 I-labeled GSH-responsive nanosystem could provide a promising strategy for lung cancer.