Hybrid nanopotentiators with dual cascade amplification for glioma combined interventional therapy.

Glioma is an aggressive malignant brain tumor with a very poor prognosis for survival. The poor tumor targeting efficiency and tumor microenvironment penetration barrier also as troubles inhibited the effective glioma chemotherapy. Here, we design a core-shell structure cascade amplified hybrid catalytic nanopotentiators CFpAD with DM1 encapsulated to overcome the glioma therapeutic obstacles. NIR laser-based BBB penetrating enhances the tumor accumulation of CFpAD. When CFpAD, as the cascade amplified drug, is treated on the cancer cells, the bomb-like CFpAD releases gold nanoparticles as glucose oxidase (GOx) and ferric oxide nanoparticles (FNPs) as peroxides (POx) after blasting, producing ROS via a cascade amplification for tumor cell apoptosis. Gold nanoparticles can rest CAFs and reduce ECM secretion, achieving deep penetration of CFpAD. Moreover, CFpAD also cuts off the nutritional supply of the tumor, reduces the pH value, and releases free radicals to destroy the cancer. The glioma cell viability was significantly decreased through DNA damage and ROS aggregation due to the DM1-based chemotherapy synergistically combined with interventional photothermal therapy (IPTT) and radiotherapy (RT). This domino cascade amplified loop, combined with starvation therapy with IPTT and RT, has good tumor penetration and outstanding antitumor efficacy, and is a promising glioma treatment system. Schematic illustration of a combined interventional therapy strategy for enhancing glioma penetration and CFpAD anti-tumor efficacy through cascade amplification. (A) Preparation of FNCp, FpA, and CFpAD. (B) The blood-brain barrier is temporarily opened with IPTT. (C) Hybrid nanopotentiators reduce interstitial fluid pressure through CAF quiescence and increase the permeability of therapeutic agents. (D) Hybrid nanopotentiators consume glucose to reduce tumor pH, produce oxygen to improve tumor hypoxia, and generate ROS to inhibit tumor proliferation. [Display omitted] • Dual cascade amplified hybrid nanopotentiators are designed for glioma. • Hybrid nanopotentiators can not only enhance the deep penetration of nanoparticle, but also enhance its catalytic ability. • Nanopotentiators have effective antitumor activity. [ABSTRACT FROM AUTHOR]