Unprecedented Theranostic LaB6 Nanocubes-Mediated NIR-IIb Photodynamic Therapy to Conquer Hypoxia-Induced Chemoresistance

Tumor hypoxia and chemoresistance are long-lasting challenges in clinical cancer treatments resulting in treatment failures and low patient survival rates. Application of phototherapies to treat deep tissue-buried tumors has been hampered by the lack of near infrared photosensitizers, and consumption of tissue oxygen, worsening the tumor hypoxia problem. Herein, an unprecedented theranostic lanthanum hexaboride-based nanodrug is engineered to act as bimodal computed tomographic/magnetic resonance imaging contrast agents, absorb long near infrared (NIR) light in the biological window IIb (1500-1700 nm), generate hydroxyl radicals without using oxygen, and destroy drug-resistant NCI-H23 lung tumors completely, leading to an amazingly long average half-life of 180 days, far exceeding than those of doxorubicin-treated (21 days) and untreated mice groups (13 days). This work pioneers the field of photodynamic therapy in conquering hypoxia and chemodrug resistance problems for NIR-IIb oxygen-independent cancer treatments.