Multi-phoretic nanomotor with consistent motion direction for enhanced cancer therapy.

Nanomotors have emerged as promising candidates for the deep penetration of loaded drugs into cancer stem cells (CSCs) located within the core of tumor tissues. A crucial factor in maximizing the clinical potential of nanomotors lies in their ability to respond dynamically to various stimuli in the tumor microenvironment. By adjusting their propulsion mechanisms in response to various stimuli, nanomotors can maintain directional movement, thus improving drug distribution and therapeutic efficacy. In this study, we present the design of a pH-responsive multi-phoretic propelled Janus nanomotor, comprising a SiO@Pt core@shell nanosphere and half-wrapped acrylic acid polymers (PAA)-conjugated gold (Au) nanoparticles (JMSNs@Pt@P-Au). The JMSNs@Pt@P-Au catalyze endogenous HO into O, propelling the nanomotors into solid tumors. Within the tumor microenvironment, the contraction of PAA triggers contact between the Au and Pt layers, facilitating self-electrophoresis propulsion. Simultaneously, a local thermal gradient is generated on the Au layer under near-infrared light irradiation, propelling the nanomotor through thermophoresis. Exploiting the unique structure of JMSNs@Pt@P-Au, the driving forces generated by HO catalysis, self-electrophoresis, and thermophoresis exhibit consistent motion directions. This consistency not only provides thrust for deep penetration but also enhances their targeted therapeutic efficiency against CSCs in vivo. This combination of nanomotor-driven power sources holds significant potential for designing intelligent, active drug delivery systems for effective CSC-targeted cancer therapy. STATEMENT OF SIGNIFICANCE: Deep penetration of nanomedicine in solid tumor tissue and cells is still an important challenge that restricts the therapeutic effect. Multiple-propelled nanomotors have been confirmed to be self-propulsive that overcome the limited penetration in solid tumor. However, their effective translation toward clinical applications is limited due to the inability to alter their propelled mechanisms in response to the actual physiological environment, resulting in speed and inconsistent movement directions. In this work, we designed a multi-phoretic propelled Janus nanomotor (JMSNs@Pt@P-Au) that exhibited three propelled mechanisms in response to the changes of pH value. Noteworthy is their heightened speed and remarkable tumor tissue penetration observed in vitro and in vivo without adverse effects. Such multi-phoretic propulsion offers considerable promise for developing advanced nanomachines with a stimuli-responsive switch of propulsion modes in biomedical applications.