The dense extracellular matrix and high interstitial pressure affect the diffusion of nanodrug in tumor tissue, resulting in a small range of action of the active components in nanodrug, thereby affecting its anticancer efficacy. In order to enhance the diffusion ability of nanodrug, a dual-bubble/photothermal-driven nanomissile (HA@MnO@TA/Fe/ICG/TPZ, HMTAFIT) was designed through "four in one" anti-tumor strategy. Harnessing the capabilities of hyaluronic acid, a biomacromolecule, the nanomotor transforms into a nanomissile, targeting cancer cells with precision. The oxygen generated by the reaction of manganese dioxide with hydrogen peroxide and the local temperature rise of indocyanine green under near-infrared light endow HMTAFIT with the ability of bubble/photothermal dual-driven, and the outermost layer of modified hyaluronic acid incubates the targeting properties of HMTAFIT which could avoid damage to normal cells. The bubble/photothermal-dual-driven increases motion speed of HMTAFIT by 13.8 μm/s, and the enhanced "four in one" anti-tumor strategy effectively improved the anticancer efficacy. The precision-guided nanomissile boasts the capability to eliminate deep-seated cancer cells and overcome multidrug resistance via optimized diffusion and a cutting-edge "four-in-one" approach.
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