Rational design and exploitation of nanomaterials with superior treatment properties for suitable indications is a way out to relieve cost constraint of therapy and solve the unsatisfactory efficacy for cancer patients. In this work, we propose a greatly facile approach to produce heterogeneous Pd-Au nanorods (Pd-Au NRs) that solve the current bottleneck problems of photothermal thermal therapy (PTT) as well as completely eliminate tumors in animal models without toxic side effects. Depositing Pd clusters on both tips of Au NRs offers Pd-Au NRs three novel functions, i.e., the extension of the absorption into NIR-II region, the activation of prodrug of 5-fluorouracil (5-Fu) via the bioorthogonal reaction, and the peroxidase-mimic activity to produce ·OH. The heterogeneous nanorods showed a high and stable photothermal conversion efficiency (52.07%) in a safer NIR-II irradiation region (1,064 nm), which not only eliminate most of tumor cells at only one dose of the irradiation for 5 min but also improve the in situ conversion of 5-fluoro-1-propargyluracil and H₂O₂ into active 5-Fu and ·OH to eradicate residual tumors for inhibiting tumor metastasis. This dual catalytic activity-synergistic mechanism of PTT demonstrates the importance of material design in solving current bottleneck problem of tumor therapy.

Studies on the influence of one critical parameter (e.g., size), targeting a specific disease, while keeping other factors unchanged, are important for improving understanding and application of the molecular design of biomedical nanomaterials. In this study, we used doxorubicin (Dox)-conjugated gold nanoparticles (GNPs) to investigate the effects of the size of the gold core (10, 20, or 60 nm) on the performance of their conjugates. We found that all three conjugates differed slightly in their physicochemical properties, facilitating a direct and accurate assessment of the size effects of GNP-Dox conjugates on their in vitro and in vivo performance. The cytological properties (the cell penetration rate and efficiency, as well as the cytotoxicity) and antitumor performance (the intratumoral penetration, treatment efficacy, and biodistribution) were highly correlated to the size of the inorganic core. Among all test groups, although the conjugate with a 60-nm gold core had the highest drug loading and release efficiency, the conjugate with a 10-nm gold core displayed the best antitumor efficacy toward the liver cancer models. This was because it showed the deepest tumor permeability and the highest tumor cell-killing ability of Dox transported by the relatively small GNPs. This study provides important evidence for better understanding the effect of size on in vitro and in vivo properties of potential therapeutic nanosystems and their structure design.