When the nanoparticles (NP4s) are injected into mice, they accumulate at the tumor site through blood circulation (passive targeting). In addition, RGD ligands on the surface interact with receptors that are highly expressed at the tumor site for active targeting. Under NIR light irradiation, a large number of ROS are generated, leading to PEG shedding and charge reversal, enabling the conversion of NP4s into core NP2s. Since NP2 have a large number of positively charged species on the surface, they can be delivered to the mitochondria, where they kill the cancer cells via photodynamic therapy (PDT). In addition, PDT also induces the immunogenic cell death (ICD) and activates CD8+ T cells for immunotherapy.
When the nanoparticles (NP4s) are injected into mice, they accumulate at the tumor site through blood circulation (passive targeting). In addition, RGD ligands on the surface interact with receptors that are highly expressed at the tumor site for active targeting. Under NIR light irradiation, a large number of ROS are generated, leading to PEG shedding and charge reversal, enabling the conversion of NP4s into core NP2s. Since NP2 have a large number of positively charged species on the surface, they can be delivered to the mitochondria, where they kill the cancer cells via photodynamic therapy (PDT). In addition, PDT also induces the immunogenic cell death (ICD) and activates CD8+ T cells for immunotherapy.

Targeting nanomedicines to cells and organelles helps drive internalization and the delivery of active drugs but remains challenging. Now a team of researchers from the Institute of Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Central South University, Peking University People’s Hospital in China and the University of Michigan in the United States have designed and synthesized core-shell polymer nanoparticles that are triggered by near infrared (NIR) light [Wei et al., Nano Today 41 (2021) 101288, https://doi.org/10.1016/j.nantod.2021.101288].

NIR radiation can penetrate deep into tissue with minimal scattering or absorption, causing little or no damage to surrounding tissue. It is, therefore, a useful means of exciting intravenous nanoparticles for photodynamic therapy or drug release or both simultaneously. The team’s approach uses novel NIR-triggered nanoparticles synthesized from a monomer with two hydroxyl groups. Two core polymers are added, one of which generates reactive oxygen species (ROS) while the other targets the mitochondria. Finally, the polymer shell is functionalized with cell surface targeting species.

When injected into model mice with triple-negative breast cancer, the core-shell polymer nanoparticles accumulate efficiently at the tumor site, according to the researchers. When irradiated with NIR light, the core-shell nanoparticles enter cancer cells, where they target the mitochondria. NIR irradiation induces the negatively charged PEG shell layer to detach from the rest of the nanoparticle and generate ROS. The ROS generated in the mitochondria result in cell death. In addition, photodynamic therapy also induces immunogenic cell death through the release of damage-associated molecular patterns (DAMPs) from tumor cells. In combination, the core-shell polymer nanoparticles combine both photodynamic therapy and immunotherapy when triggered by NIR irradiation.

The team show that tumor-bearing mice injected with the core-shell polymer nanoparticles and triggered with NIR irradiation saw a significant reduction in tumor size, with otherwise no loss in body weight. The results indicate that the approach inhibits tumor growth without inducing significant toxicity to the rest of the organism. The survival rate of the mice was 80% after 60 days compared with the control group, which all died within 35 days.

The core-shell polymer nanoparticles appear to combine excellent tumor targeting and therapeutic effects when triggered with NIR irradiation with negligible toxicity to the whole organisam. The researchers believe their approach offers a novel means of improving combined photodynamic and immuno-therapy in the treatment of tumors.