Upconversion photodynamic therapy (UC‐PDT), which integrates upconversion nanoparticles (UCNPs) with photosensitizers (PSs), presents a promising advancement in the field of phototherapy. However, despite the extensive studies focused on the design and synthesis of UCNPs, there is a paucity of systematic research on the mechanisms underlying the synergistic upconversion photodynamic effects. Here we have synthesized upconversion core@dotted‐shell nanoparticles (CDSNPs) and covalently tethered them with two distinct PSs, thereby constructing a dual‐PS UC‐PDT system with high synergistic photodynamic performance. To unravel the mechanism underlying the synergism, we employed a combination of quantum mechanical calculations and ultrafast time‐resolved spectroscopy techniques. The results indicate that rare earth oxides play a pivotal role in enhancing the intersystem crossing processes of PSs through modulating their excited electronic states. Additionally, Förster resonance energy transfer between two distinct PSs contributes to the amplification of triplet state populations, thus further enhancing the photodynamic effect. In vitro experiments demonstrate that the prepared CDSNPs based dual‐PS system exhibits excellent biocompatibility with normal cells and exceptional synergistic photodynamic efficacy against tumor cells upon near‐infrared excitation. This research contributes theoretical insights into the design and application of multi‐photosensitizer UC‐PDT systems, laying the groundwork for more efficient preclinical implementations in the future.

We report a novel multi-functional nanoarchitecture of Gd₂O₃:Dy³⁺ shell on silica core that enables unique multi-color living cell imaging and remarkable in vivo magnetic resonance imaging.

Multifunctional nanoprobes, due to their unique nanocomposite structures, have prominent advantages that combine multimodal imaging of a tumor with photothermal therapy. However, they remain a challenge for constructing nanostructures via conventional approaches due to the peculiar environmental sensitivity of each component. Here, we report the design and synthesis of Gd-based nanoparticle-tailored gold nanorods with distinctive core–shell and dumbbell nanoarchitectures (NAs) by a specific synthesis technology. The prepared NAs possess a tunable particle size of 80–120 nm in length and 50–90 nm in diameter, which are suitable for cellular uptake and passive targeting of a tumor. The formation of two distinct heterostructures and their underlying mechanism were studied through systematic investigations on the controllable synthesis process. The as-prepared nanoprobes possess an ultrahigh longitudinal relaxivity (r₁) of 22.69 s⁻¹ mM⁻¹ and thus a significant magnetic resonance imaging signal enhancement has been observed in mice tumors. The NAs, especially the dumbbell type, show a vivid two-photon cell imaging and a remarkable photothermal conversion efficiency owing to their superior longitudinal surface plasmon resonance. Both in vitro cytotoxicity and in vivo immunotoxicity assays give substantial evidence of excellent biocompatibility attained in the NAs. The development of multifunctional targeting nanoprobes in this study could provide guidance for tailored design and controllable synthesis of heterostructured nanocomposites utilized for multimodal imaging and photothermal therapy of cancer.

With ongoing advancements in photothermal therapy, achieving efficient tumor cell eradication while minimizing damage to healthy tissues necessitates a highly effective and non-invasive real-time temperature monitoring technique for human tissues. Herein, we report a near-infrared (NIR)-II optical temperature sensing nanoprobe featuring rare-earth-doped gadolinium oxide nanocrystals (RENCs) attached to the dumbbell mesoporous silica-coated gold nanorods (AuNRs). The composite nanoprobe presents an intense absorption in the NIR region, and NIR-II photoluminescence (PL) increases by 97.2 to 102-fold compared to pure RENCs upon 980 nm irradiation. The localized electric field generated through surface plasmon resonance effects of AuNRs demonstrated a dumbbell-shaped distribution that aligns with the structure of nanoprobes, maximizing the PL enhancement of RENCs. Moreover, the NIR-II emissions are changed with the rising temperature, with an exceptional relative sensitivity of 7.25% K⁻¹ at 338 K based on PL lifetime, indicating the nanoprobe is highly potential for optical temperature sensing.