Until now, treatment of refractory tumors and uncontrolled metastasis by cancer immunotherapy has not yet achieved satisfactory therapeutic results due to the insufficient in vivo immune response. Here, we proposed the construction of a therapeutic cancer nanovaccine Fe@OVA-IR820 with ferroptosis-inducing and photothermal properties for boosting cancer immunotherapy. Fe3+ ions were chelated inside the exogenous antigen ovalbumin (OVA) by biomineralization to form the nanovaccine, to which the photosensitizer IR820 was loaded by electrostatic incorporation. After intratumoral injection, in situ immunogenic cell death (ICD) was triggered as a result of Fe3+-dependent ferroptosis. Endogenous neoantigens and damage-associated molecular patterns (DAMPs) were released because of ICD and worked synergically with the exogenous OVA to provoke the immune response, which was further amplified by the photothermal effect after near-infrared irradiation. The enhanced recruitment and infiltration of T cells were observed and resulted in the suppression of the primary tumor. The therapeutic regiment that combined Fe@OVA-IR820 nanovaccine with cytotoxic T lymphocyte-associated protein 4 (CTLA-4) checkpoint blockade significantly boosted anti-cancer immunity and inhibited the growth of distal simulated metastases. Therefore, we proposed Fe@OVA-IR820 nanovaccine combined checkpoint blockade as a potential therapeutic strategy for melanoma treatment.
Metal-doped iron oxide nanoparticles have attracted increasing attention for their Fenton reaction ability, which converts H 2 O 2 to cytotoxic reactive oxygen species (ROS) and is recently utilized as ferroptosis activator in pancreatic cancer therapy. However, low intracellular H 2 O 2 level hinders ferroptosis effect and leads to unsatisfactory efficacy. Herein, a transferrin coated and tumor homing peptide decorated bimetallic magnetic nanoparticles copper-doped iron oxide nanosystems embedded with photothermal agent IR820 and iron ions (denoted as PCTIFL) is constructed for synergistic treatment for pancreatic cancer by combining ferroptosis and photothermal/photodynamic therapy (PTT/PDT) under 808 nm laser irradiation. Benefiting from the homologous targeting property of LyP-1, the nanosystems can be precisely delivered and gradually accumulate at tumor site. For the synergistic therapy, IR820 generates ROS via photodynamic effect and enables cancer cell temperature elevation via PTT effect upon 808 nm laser irradiation on the one hand and metal ions such as Fe 2+ , Fe 3+ and Cu 2+ catalyze H 2 O 2 into ROS and finally triggered ferroptosis on the other hand. Moreover, PCTIFL nanosystems can be applied in pancreatic cancer diagnosis for their MRI/NIR dual imaging function. Overall, this work not only presents a promising strategy for augmenting the ferroptosis induced by iron oxide, but also a fantastic paradigm for pancreatic cancer diagnosis and synergistic therapy.
A diagnosis and therapeutic strategy for gastric cancer is developed herein by combining thermosensitive liposomal (TSL)-based photothermal/photodynamics therapy (PTT/PDT) with chemotherapy and adjuvant immunotherapy. IR820, a photothermal agent, paclitaxel (PTX), an antitumor drug, and imiquimod (R837), a Toll-like-receptor-7 agonist, are coencapsulated into a TSL drug delivery system. These formed PTX-R837-IR820@TSL complexes exhibit excellent optical properties, good dispersibility, and stability. Under NIR light irradiation, the measurement of singlet oxygen production and thermal efficiency indicate promising potential of PTX-R837-IR820@TSL complexes for PTT and PDT. Confocal microscopy and small animal NIR imaging demonstrate tumor targeting ability of the liposomal complexes to gastric cancer cells. In vitro cell viability assays and in vivo animal experiments show prominent antitumor efficiency of PTX-R837-IR820@TSL complexes upon NIR light irradiation. This excellent therapeutic efficacy is attributed to the simultaneous chemotherapy and PTT/PDT. Furthermore, the liposomal complexes under NIR irradiation would ablate tumors to generate a pool of tumor-associated antigens, which is able to promote strong antitumor immune responses in the presence of those R837-containing liposomal complexes acted as adjuvant. These results indicate that the multifunctional liposomal complexes could realize a remarkable synergistic therapeutic outcome in gastric carcinoma.
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