Gold mineralized “hybrid nanozyme bomb” for NIR-II triggered tumor effective permeation and cocktail therapy

Lung cancer is one of the most common malignant tumors with the fastest increase in the incidence rate and mortality. Even after maximum tumor resection assistance with a radiotherapy and chemotherapy combination, the recurrence of non-small cell lung cancer is still inevitable. In addition, low targeting efficiency and poor permeability of drug Deliv. systems strongly affect the therapeutic efficiency of anti-cancer drugs on non-small cell lung cancer. Here we designed a gemcitabine (GEM) loaded arginine-glycine-aspartic acid-cysteine (RGDc)-modified gold mineralization “hybrid nanozyme bomb” (RGTG) to overcome those obstacles. RGDc modification improved the active targeting of liposomes to the tumor tissues with the second near-infrared (NIR-II)-triggered gold-shell disruption and GEM release. The collapsed gold-shell particles with a smaller size could penetrate the tumor solid barrier and act as photothermal therapy (PTT) agents to improve PTT therapy and starvation therapy via generating gluconic acid and reactive oxygen species (ROS). Moreover, the resting reversal effect of gold particles on tumor fibroblasts can achieve accelerating tumor penetration of gold particles and GEM. Compared to monotherapy, RGTG showed significant improvement in tumor inhibition, with a tumor volume reduction of 83% compared to the control group, which provides a promising tumor treatment platform for non-small cell lung cancer (NSCLC).