Herein, a functional class of microenvironment-associated nanomaterials is reported for improving the second near-infrared (NIR-II) imaging and photothermal therapeutic effect on intracranial tumors via a spontaneous membrane-adsorption approach. Specific peptides, photothermal agents, and biological alkylating agents were designed to endow the nanogels with high targeting specificity, photothermal properties, and pharmacological effects. Importantly, the frozen scanning electron microscopy technology (cryo-SEM) was utilized to observe the self-association of nanomaterials on tumor cells.