The development of effective nanoplatforms is extremely necessary for cancer therapy. Herein, we prepared polydopamine (PDA) and ammonium bicarbonate (NH₄HCO₃) coated and doxorubicin (Dox) loaded hollow cerium oxide (CeO₂) NPs (PDAC NPs), which showed excellent synergistic effect for photothermal therapy, chemotherapy and chemodynamic therapy. Under near infrared laser irradiation, PDA shell could absorb the incident light and convert it into heat, which could not only kill tumor cells with hyperthermia, but also trigger the decomposition of NH₄HCO₃ into gaseous carbon dioxide and ammonia, leading to the destroy of PDA shell. The leakage of PDA further accelerated Dox release and exposed CeO₂ surface, in which Dox could enter into cell nucleus to induce chemotherapy, and CeO₂ could catalyze cellular hydrogen peroxide into hydroxyl radical to present chemodynamic therapy. In fact, PDAC NPs showed an excellent therapeutic efficacy both in vitro and in vivo. This design provides a new strategy for synergistic tumor therapy.

The particular physicochemical properties of nanomaterials are able to elicit unique biological responses. The property activity relationship is usually established for in-depth understanding of toxicity mechanisms and designing safer nanomaterials. In this study, the toxic role of specific crystallographic facets of a series of polyhedral lead sulfide (PbS) nanocrystals, including truncated octahedrons, cuboctahedrons, truncated cubes, and cubes, was investigated in human bronchial epithelial cells (BEAS-2B) and murine alveolar macrophages (RAW 264.7) cells. {100} facets were found capable of triggering facet-dependent cellular oxidative stress and heavy metal stress responses, such as glutathione depletion, lipid peroxidation, reactive oxygen species (ROS) production, heme oxygenase-1 (HO-1) and metallothionein (MT) expression, and mitochondrial dysfunction, while {111} facets remained inert under biological conditions. The {100}-facet-dependent toxicity was ascribed to {100}-facet-dependent lead dissolution, while the low lead dissolution of {111} facets was due to the strong protection afforded by poly(vinyl pyrrolidone) during synthesis. Based on this facet-toxicity relationship, a "safe-by-design" strategy was designed to prevent lead dissolution from {100} facets through the formation of atomically thin lead-chloride adlayers, resulting in safer polyhedral PbS nanocrystals.