Positive Chemotaxis of CREKA-Modified Ceria@Polydopamine Biomimetic Nanoswimmers for Enhanced Penetration and Chemo-photothermal Tumor Therapy

Tumor interstitial pressure represents the greatest barrieragainstdrug diffusion into the depth of the tumor. Biometric nanomotors highlightthe possibility of enhanced deep penetration and improve cellularuptake. However, control of their directionality remains difficultto achieve. Herein, we report cysteine-arginine-glutamic acid-lysine-alanine(CREKA)-modified ceria@ polydopamine nanobowls as tumormicroenvironment-fueled nanoscale motors for positive chemotaxis intothe tumor depth or toward tumor cells. Upon laser irradiation, thisnanoswimmer rapidly depletes the tumor microenvironment-specific hydrogenperoxide (H2O2) in the nanobowl, contributingto a self-generated gradient and subsequently propulsion (9.5 & mu;m/sat 46 & DEG;C). Moreover, the asymmetrical modification of CREKA onnanobowls could automatically reconfigure the motion direction towardtumor depth or tumor cells in response to receptor-ligand interaction,leading to a deep penetration (70 & mu;m in multicellular spheroids)and enhanced antitumor effects over conventional nanomedicine-inducedchemo-photothermal therapy (tumor growth inhibition rate: 84.2% versus56.9%). Thus, controlling the direction of nanomotors holds considerablepotential for improved antitumor responses, especially in solid tumorswith high tumor interstitial pressure.