Reactive Oxygen Correlated Chemiluminescent Imaging of a Semiconducting Polymer Nanoplatform for Monitoring Chemodynamic Therapy.

In chemodynamic therapy (CDT), real-time monitoring of reactive oxygen species (ROS) production is critical to reducing the nonspecific damage during CDT and feasibly evaluating the therapeutic response. However, CDT agents that can emit ROS-related signals are rare. Herein, we synthesize a semiconducting polymer nanoplatform (SPN) that can not only produce highly toxic ROS to kill cancer cells but also emit ROS-correlated chemiluminescent signals. Notably, the efficacy of both chemiluminescence and CDT can be significantly enhanced by hemin doping (∼10-fold enhancement for luminescent intensity). Such ROS-dependent chemiluminescence of SPN allows ROS generation within a tumor to be optically monitored during the CDT process. Importantly, SPN establishes an excellent correlation of chemiluminescence intensities with cancer inhibition rates in vitro and in vivo. Thus, our nanoplatform represents the first intelligent strategy that enables chemiluminescence-imaging-monitored CDT, which holds potential in assessing therapeutic responsivity and predicting treatment outcomes in early stages.

Cyclic Amplification of the Afterglow Luminescent Nanoreporter Enables the Prediction of Anti-cancer Efficiency.

We developed a cyclic amplification method for an organic afterglow nanoreporter for the real-time visualization of self-generated reactive oxygen species (ROS). We promoted semiconducting polymer nanoparticles (PFODBT) as a candidate for emitting near-infrared afterglow luminescence. Introduction of a chemiluminescent substrate (CPPO) into PFODBT (PFODBT@CPPO) resulted in a significant enhancement of afterglow intensity through the dual cyclic amplification pathway involving singlet oxygen (1 O2 ). 1 O2 produced by PFODBT@CPPO induced cancer cell necrosis and promoted the release of damage-related molecular patterns, thereby evoking immunogenic cell death (ICD)-associated immune responses through ROS-based oxidative stress. The afterglow luminescent signals of the nanoreporter were well correlated with light-driven 1 O2 generation and anti-cancer efficiency. This imaging strategy provides a non-invasive tool for predicting the therapeutic outcome that occurs during ROS-mediated cancer therapy.

A two-photon fluorescence self-reporting black phosphorus nanoprobe for the in situ monitoring of therapy response.

The in situ and real-time supervision of reactive oxygen species (ROS) generated during photodynamic therapy (PDT) is of great significance for lessening nonspecific damage and guiding personalized therapy. However, photosensitizers frequently fail to deliver successful treatment accompanying the ROS-related imaging signals produced, impeding simple treatment outcome predictions and therapeutic schedule adjustments. Here, we report a two-photon fluorescence self-reporting strategy for the in situ and real-time monitoring of treatment response via a novel black phosphorus-based two-photon nanoprobe (TPBP). TPBP effectively generated singlet oxygen (1O2) under near-infrared laser irradiation for PDT, and 1O2 stimulated a two-photon molecule to emit fluorescence signals for feedback of 1O2 generation, which facilitated the regulation of treatment parameters to achieve precise and personalized medicine in deep tissue.

In vivo therapeutic response monitoring by a self-reporting upconverting covalent organic framework nanoplatform.

The real-time and in situ monitoring of reactive oxygen species (ROS) generation is critical for minimizing the nonspecific damage derived from the high doses of ROS required during the photodynamic therapy (PDT) process. However, phototherapeutic agents that can generate ROS-related imaging signals during PDT are rare, hampering the facile prediction of the future therapeutic outcome. Herein, we develop an upconverting covalent organic framework (COF) nanoplatform via a core-mediated strategy and further functionalized it with a singlet oxygen reporter for the efficient near-infrared activated and in situ self-reporting of PDT. In this work, the COF photodynamic efficacy is greatly improved (12.5 times that of irregular COFs) via tailoring the size. Furthermore, this nanoplatform is able to not only produce singlet oxygen for PDT, but it can also emit singlet oxygen-correlated luminescence, allowing the real-time and in situ monitoring of the therapeutic process for cancer cells or solid tumors in vivo via near-infrared luminescence imaging. Thus, our core-mediated synthetic and size-tailored strategy endows the upconverting COF nanoplatform with promising abilities for high-efficacy, deep-tissue, precise photodynamic treatment.