Environmentally responsive multistage gas/enzyme/NIR-driven chemotactic transport nanorockets for single wavelength procedural combination therapy

The high viscosity and deep-seated conditions of tumor tissues have led to the ineffective delivery of anti-cancer drugs. In order to improve the anti-tumor efficacy, we have developed a multistage gas/ enzyme/Near-infrared light driven nanorocket (HA@MnCuGOD@MSN@DIN) for the procedural combination of photodynamic therapy, photothermal therapy, starvation therapy, chemodynamic therapy, and chemotherapy. The nanorocket is multistage driven to achieve deep penetration of tumor tissue under the conditions of high glucose concentration, acidic microenvironment, and local high temperature. Specifically, the first stage is CO2 gas-driven, using enhanced diffusion from gases release by the acidresponse of MnCO3, while Fenton-like reaction of the released Mn(II) with H2O2 can achieve chemodynamic therapy; the second stage is enzyme-driven which is realized by efficient enzymatic reaction of glucose oxidase and glucose; the last stage is CO2/NH3 gas-driven produced by NH4HCO3 at NIR 808 nm or in an acid environment. With the multistage gas/enzyme-driven, the movement speed was increased from 11 mm/s to 30 mm/s, and the excellent deep puncture ability combined with procedural combination therapy effectively improves the anticancer efficacy. The application of multistage gas/enzyme/NIRdriven chemotactic transport nanorockets opens a new chapter in the field of deeply penetrating cancer treatment through procedural combination therapy.