Abstract

Lung cancer has the highest global incidence and mortality, with nonsmall cell lung cancer (NSCLC) as the predominant subtype. Traditional therapies are limited by drug resistance, systemic toxicity, and poor precision. Active ingredients from Chinese herbs offer promising alternatives. This work identified kaempferol (KAE) from Tetrastigma hemsleyanum Diels et Gilg as an anti-NSCLC agent and developed a pH/photothermal dual-responsive nanocarrier (KMPB@PL-HA) for targeted therapy. The nanocarrier uses mesoporous Prussian blue (MPB) as the photothermal core, polylysine (PLL), and ultra-active hyaluronic acid (UL-HA) as the pH-responsive shell. In the tumor microenvironment (TME), UL-HA binds to CD44 receptors overexpressed on NSCLC cells and dissociates, while PLL enhances cellular uptake via electrostatic adsorption. KAE induces mitochondrial apoptosis via p-Akt inhibition, Bax/Bcl-2 regulation, and caspase cascade activation, and downregulates VEGF and modulates TME redox homeostasis for synergistic antitumor effects. This study provides a novel chemo-photothermal synergistic strategy for NSCLC.