Self‐Amplified Drug Delivery with Light‐Inducible Nanocargoes to Enhance Cancer Immunotherapy

다국어 초록 (Multilingual Abstract)

Chemoimmunotherapy by systemic administration of individual regimens suffers from inconsistent pharmacokinetics profiles, low tumor specificity, and severe side effects. Despite promising nanoparticle‐based codelivery approaches in therapeutics, the pathophysiological barriers of solid tumors are a hurdle for tumor accumulation and deep penetration of the drug‐loaded nanoparticles. A light‐inducible nanocargo (LINC) for immunotherapy is reported. LINC is composed of a reduction‐responsive heterodimer of photosensitizer pheophorbide A (PPa) and indoleamine 2,3‐dioxygenase 1 (IDO‐1) inhibitor, i.e., NLG919, and a light‐activatable prodrug of oxaliplatin (OXA). LINC administrated through intravenous injection is passively accumulated at the tumor site to generate near‐infrared (NIR) fluorescence signal. Under fluorescence imaging guidance, the first‐wave of NIR laser irradiation induce reactive oxygen species (ROS) generation, trigger cleavage of the polyethylene glycol (PEG) corona, and thus promote tumor retention and deep penetration of LINC. When exposed to the second‐wave NIR laser illumination, LINC efficiently elicits the immune response and promotes intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Furthermore, NLG919 delivered by LINC reverses the immunosuppressive tumor microenvironment by suppressing IDO‐1 activity. Chemoimmunotherapy with LINC inhibit the tumor growth, lung metastasis, and tumor recurrence. The light‐inducible self‐amplification strategy for improved drug delivery and immunotherapy shows potential.
Light‐inducible prodrug nanocargoes (LINC) are reported for self‐amplified drug delivery and improved cancer immunotherapy. LINC in combination with two‐wave laser irradiation efficiently induce immunogenic cell death (ICD) and suppress the activity of indoleamine 2,3‐dioxygenase 1 (IDO‐1) of the tumor cells. Combination immunotherapy by LINC significantly inhibits tumor growth, suppresses lung metastasis, and prevents tumor recurrence by eliciting immune responses and overcoming the immunosuppressive tumor microenvironment.