An Activatable Near‐Infrared Afterglow Theranostic Prodrug with Self‐Sustainable Magnification Effect of Immunogenic Cell Death

Abstract

Herein, we report an activatable near-infrared (NIR) afterglow theranostic prodrug that circumvents high background noise interference caused by external light excitation. The prodrug can release hydroxycamptothecin (HCPT) in response to the high intratumoral peroxynitrite level associated with immunogenic cell death (ICD), and synchronously activate afterglow signal to monitor the drug release process and cold-tohot tumor transformation. The prodrug itself is an ICD inducer achieved by photodynamic therapy (PDT). PDT initiates ICD and recruits first-arrived neutrophils to secrete peroxynitrite to trigger HCPT release. Intriguingly, we demonstrate that HCPT can significantly amplify PDT-mediated ICD process. The prodrug thus shows a self-sustainable ICD magnification effect by establishing an "ICD-HCPT release-amplified ICD" cycling loop. In vivo studies demonstrate that the prodrug can eradicate existing tumors and prevent further tumor recurrence through antitumor immune response.

Microneedle Device Delivering Aggregation-Induced Emission Photosensitizers for Enhanced Metronomic Photodynamic Therapy of Cancer

“…The inability of immune cells to effectively enter inside the tumor may also be one of the reasons for the ineffectiveness of anti-PD-L1. PDT can effectively promote the infiltration of immune cells in tumor tissues, , therefore, in the M-mPDT group, immune cells were found inside the tumor tissues. More importantly, the combination of M-mPDT and anti-PD-L1 not only boosted the number of CD4 + and CD8 + cells but also effectively promoted tumor infiltration of these immune cells.…”

Immunogenic Cell Death in Hematological Malignancy Therapy

“…Additionally, near-infrared afterglow theranostics can be used not only for surgical treatment but also to mediate tumor death by inducing sustained amplification of ICD. [94,95] The induction of ICD having been discussed, assays for ICD can be summarized as having three main strategies (Figure 2): to assess excitation of DAMPs signaling and associated stressors in dying cells, to assess the activation of APCs and their function in mediating cross-reactivity in vivo and in vitro, and to assess the ability of dying cells to mount an adaptive immune response in an immunocompetent homologous host. [5] ICD has been well described in solid tumors.…”

“…Additionally, near‐infrared afterglow theranostics can be used not only for surgical treatment but also to mediate tumor death by inducing sustained amplification of ICD. [ 94,95 ]…”

Synthesis of nitrogen mustard-based fluorophores for cell imaging and cytotoxicity studies

“…They can be used not only for real-time imaging but also as a therapeutic agent. [ 8 ] However, many treatment agents turn to lack effective luminescent units generating valid fluorescence. Although there are many fluorescent molecules emerging continuously, the stokes shift turn to be small and the emission wavelength is generally short.…”