Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle

Abstract

Though immunogenic cell death (ICD) has garnered significant attention in the realm of anticancer therapies, effectively stimulating strong immune responses with minimal side effects in deepseated tumors remains challenging. Herein, we introduce a novel selfassembled near-infrared-light-activated ruthenium(II) metallacycle, Ru1105 (λ em = 1105 nm), as a first example of a Ru(II) supramolecular ICD inducer. Ru1105 synergistically potentiates immunomodulatory responses and reduces adverse effects in deep-seated tumors through multiple regulated approaches, including NIR-light excitation, increased reactive oxygen species (ROS) generation, selective targeting of tumor cells, precision organelle localization, and improved tumor penetration/ retention capabilities. Specifically, Ru1105 demonstrates excellent depth-activated ROS production (∼1 cm), strong resistance to diffusion, and anti-ROS quenching. Moreover, Ru1105 exhibits promising results in cellular uptake and ROS generation in cancer cells and multicellular tumor spheroids. Importantly, Ru1105 induces more efficient ICD in an ultralow dose (10 μM) compared to the conventional anticancer agent, oxaliplatin (300 μM). In vivo experiments further confirm Ru1105's potency as an ICD inducer, eliciting CD8 + T cell responses and depleting Foxp3 + T cells with minimal adverse effects. Our research lays the foundation for the design of secure and exceptionally potent metal-based ICD agents in immunotherapy.

A Review of Image Sensors Used in Near-Infrared and Shortwave Infrared Fluorescence Imaging

“…These factors result in high-resolution imaging at greater penetration depth than is achievable in the NIR window. Since in vivo SWIR fluorescence imaging is a relatively new field of research, only a few SWIR fluorophores were developed, including single-walled carbon nanotubes (SWNTs) [ 9 , 10 ], QDs [ 11 ], rare earth-doped nanoparticles [ 12 ], polymeric nanoparticles [ 13 ], ruthenium (II) metallacycle [ 14 , 15 ], and small-molecule water-soluble dyes [ 16 ]. However, none of these SWIR fluorescent agents have been approved for clinical applications.…”

Metal–organic framework (MOF)-based materials for pyroptosis-mediated cancer therapy

“…, immune-active) to promote antigen presentation, dendritic cell (DC) maturation, T lymphocyte activation, and infiltration, and further stimulate the systemic immune function against the tumor. 14–16 Noteworthily, the treatment with chemotherapeutic drugs ( e.g. , cisplatin, 17 doxorubicin (DOX), 18 metformin, 19 etc. )…”

An NIR Type I Photosensitizer Based on a Cyclometalated Ir(III)-Rhodamine Complex for a Photodynamic Antibacterial Effect toward Both Gram-Positive and Gram-Negative Bacteria

“…More importantly, the O 2 –· species generated via the type I process not only function as oxidants for eliminating tumor cells but also participate in superoxide dismutase-mediated catalytic cascades, generating highly cytotoxic ·OH species while simultaneously replenishing oxygen through recycling mechanisms . So far, a few groups have reported type I organic photosensitizers based on BODIPY, − Nile Blue analogs, ,, fluorescein, phthalocyanine, cyclometalated Ru­(II), cyclometalated Ir­(III), , some D–A structures, − and so on . However, it still remains a challenge to design type I PSs owing to the lack of a general design strategy. , Rhodamines exhibit many desirable attributes as PSs for PDT, such as high extinction coefficients, excellent biocompatibility, and resistance to photobleaching. − However, a type I PS based on rhodamine has been rarely reported.…”

“…So far, a few groups have reported type I organic photosensitizers based on BODIPY, − Nile Blue analogs, ,, fluorescein, phthalocyanine, cyclometalated Ru­(II), cyclometalated Ir­(III), , some D–A structures, − and so on . However, it still remains a challenge to design type I PSs owing to the lack of a general design strategy. , Rhodamines exhibit many desirable attributes as PSs for PDT, such as high extinction coefficients, excellent biocompatibility, and resistance to photobleaching. − However, a type I PS based on rhodamine has been rarely reported. Thus, it is desirable and valuable to develop new type I PSs based on rhodamine derivatives.…”