Carbon nanocages-based nanozyme as an endogenous H2O2-activated oxygenerator for real-time bimodal imaging and enhanced phototherapy of esophageal cancer
Intelligent phototherapy of theranostic nanosystems that can be activated by tumor microenvironment possesses higher sensitivity and specificity. However, hypoxia and low drug accumulation in tumors greatly limit its clinical application. Herein, we designed a cage-like carbon-manganese nanozyme, which could effectively relieve tumor hypoxia and deliver numerous photosensitizers (PSs) to the tumor site, for real-time imaging and enhanced phototherapy of esophageal cancer. Specifically, bovine serum albumin (BSA) was used as a template and reducing agent for preparing BSA-MnO2 nanozyme, then BMIOC nanosystem was successfully synthesized by crosslinking BSA-MnO2 on the surface of IR820-loaded carboxylated carbon nanocages (OCNCs). Abundant PSs were successfully delivered to tumor sites via hollow OCNCs, and the final loading rate of IR820 reached 42.8%. The intratumor BMIOC nanosystem can be initiated by tumor microenvironment to switch on its magnetic resonance (MR) imaging signal, photothermal therapy (PTT) and photodynamic therapy (PDT) function. Notably, the BSA-MnO2 nanozyme, with intrinsic catalase (CAT) -like activity, catalyzed endogenous H2O2 for oxygen generation to surmount tumor hypoxia and enhance PDT, thereby leading to more efficient therapeutic effects in combination with OCNCs-elevated PTT. Besides, the H2O2-activated and acid-enhanced properties enable our nanosystem to be specific to tumors, protecting normal tissues from damage. By integrating high drug loading capacity, hypoxia regulation function, enlarged phototherapy effect, and bimodal imaging into a nanozyme-mediated nanoreactor, this work realizes “one for all” and represents a promising clinical translation for efficient esophageal cancer theranostics.