Dual-responsive nanomotors for deep tumor penetration and subcellular arrangement.

[Display omitted] • The novel rocket-like Janus-type CuS-ZIF-8-Dox JNPs were synthesized by a dual-solvent method. • The self-propelled CuS-ZIF-8-Dox JNPs penetrated deep tumor due to NIR-induced local thermal gradient. • Each component of CuS-ZIF-8-Dox JNPs showed specific optimal subcellular localization after cell internalization. The tumor tissue delivery of nanomaterials and the components' intracellular location are particularly critical for the effect of tumor treatment. However, the abominable conditions in the tumor microenvironment hinder nanomaterials' penetration, inducing the therapeutic action only on the surface of tumor tissue. And it is low-efficiency for therapy to spread nanomaterials in relatively expansive cytoplasm or organelles nonspecifically. Herein, we employed a near-infrared (NIR) light-induced self-propelled doxorubicin-loaded zeolitic imidazolate framework-8 capped copper sulfide Janus nanoparticles (CuS-ZIF-8-Dox JNPs) for deep tumor penetration and cancer therapy. The rocket-like Janus structure was rapidly synthesized by a dual-solvent method. Under NIR light irradiation, the rocket-like CuS-ZIF-8 JNPs showed directional wide-range motion. In addition, benefiting from the pH-responsive degradation of ZIF-8, various components were conveyed to the appropriate locations after cell internalization, i.e. , Dox targeted the nucleus, and CuS nanoparticles escaped from lysosomes to the cytoplasm. Taking advantage of the local thermal gradient under the NIR light irradiation and intracellular arrangement for different components, this Janus nanocomposite displayed a deep tumor penetration, and achieved NIR and pH dual-responsive photothermal-enhanced chemodynamic therapy and chemotherapy in vitro and in vivo. [ABSTRACT FROM AUTHOR]