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.