A novel afterglow nanoreporter for monitoring cancer therapy

Abstract

Rationale: Immunogenic cell death (ICD)-associated immunogenicity evoked through reactive oxygen species (ROS) is an efficient way to fight against the immune-dysfunctional microenvironment, so as to provoke potent anti-tumor immunity. However, the unknown ROS dose during cancer therapies may induce adverse immune responses (e.g., insufficient ICD, toxicity toward normal tissues or immune system). Methods: Herein, we developed a pyrido pyrazine - thiophene based semiconducting polymer as novel near-infrared (NIR) organic afterglow nanoparticles for the real-time visualization of self-generated ROS, during photodynamic-mediated immunogenic cell death. Specifically, we introduced the strong “acceptor” (pyrido pyrazine) into thiophene based semiconducting polymer to redshift emission wavelength, and further modulate the “donor” to afford more afterglow reaction sites and reducing ΔEst, so as to enhance luminescence intensity. Results: The semiconducting polymer-based afterglow nanoparticles exhibit strong afterglow emission with longer-wavelength emission (> 800 nm), compared with the reported organic afterglow nanoparticles (e.g., MEHPPV, PFODBT or Chlorin, < 690 nm), which endows this afterglow nanoparticles with a greatly improvement of signal to noise ratio. Moreover, the photodynamic effect of this afterglow nanoparticles can induce immunogenic cell death of cancer cells and further cause immune responses in mice. Conclusions: The NIR afterglow signal presents a good relationship with ROS generation, immunogenic cell death and outcome of treatment. Therefore, it was able to provide a non-invasive tool for predicting the degree of ICD that occurs during ROS-mediated cancer therapy and may contribute to precise immunotherapy.

Combined Cancer Immunotheranostic Nanomedicines: Delivery Technologies and Therapeutic Outcomes

“…Afterglow luminescence has been widely employed for in vivo imaging, including cell tracking, biodetection, and lymph node localization with a noninvasive method. Liao et al designed novel NIR-3 organic afterglow nanoparticles based on pyrido pyrazine and thiophene for the real-time imaging of self-generated ROS during photodynamic-mediated ICD . Singlet oxygen produced from SPN (NIR-3) not only contributed to the afterglow emission process but also had the ability to induce effective ICD, which was coupled with the generation of DAMPs, increasing cancer cell antigenicity.…”

“…Additionally, with the maximal dose of the SPN­(NIR-3)-treated group compared to the control group, the level of immune-relevant cytokines in the spleen, including IL-6 and TNF-a, increased by about 3 and 4.5 times, respectively. Additionally, tumor slice immunofluorescence labeling of CRT indicated that one of the distinguishing features of ICD caused by the photodynamic impact of SPN­(NIR-3) in vivo was the translocation of CRT to the cell membrane surface …”

“…Liao et al designed novel NIR-3 organic afterglow nanoparticles based on pyrido pyrazine and thiophene for the real-time imaging of self-generated ROS during photodynamic-mediated ICD. 70 Singlet oxygen produced from SPN (NIR-3) not only contributed to the afterglow emission process but also had the ability to induce effective ICD, which was coupled with the generation of DAMPs, increasing cancer cell antigenicity. Additionally, there was a strong correlation between afterglow signals and 1O2 production, ICD levels, and cancer inhibition rates.…”

“…Additionally, tumor slice immunofluorescence labeling of CRT indicated that one of the distinguishing features of ICD caused by the photodynamic impact of SPN(NIR-3) in vivo was the translocation of CRT to the cell membrane surface. 70 …”

Organic Afterglow Nanoparticles in Bioapplications

“…When researchers carried out experiments on some organic semiconductors containing thiophene groups, it was found that they have afterglow properties, which can be self‐assembled into semiconductor polymer nanoparticles (SPNs) by nanoprecipitation with an amphiphilic triblock copolymer of surfactant. Poly[2,7‐(9,9’‐dioctylfluorene)‐alt‐4,7‐bis(thiophen‐2‐yl) benzo‐2,1,3‐thiadiazole] (PFODBT) is an organic afterglow material very well‐known and very well reported [44,45] . The thiophene group in PFODBT reacts with singlet oxygen ( 1 O 2 ) to form an unstable thiophene‐dioxetane intermediate, which is prone to cleavage and induces afterglow from other PFODBT nanoparticles through chemically initiated electron exchange luminescence (CIEEL).…”