Construction of Nucleus‐Targeting Iridium Nanocrystals for Photonic Hyperthermia‐Synergized Cancer Radiotherapy

Abstract Prominent tumor‐cell nucleus targeting of radiosensitizer substantially affects the therapeutic consequence of advanced tumor radiotherapy via lethal nucleus DNA damage. Herein, ultrasmall iridium nanocrystals (Ir NCs, <5 nm) are constructed for efficient tumor‐specific photonic hyperthermia‐synergized radiotherapy. To endow the NCs with qualified cell nucleus‐targeting performance, polyethylene glycol (PEG)‐modified Ir NCs are decorated with α v β 3 integrin‐targeting cyclic arginine‐glycine‐aspartic (c(RGDyC)), designated as RGD, peptides and human immunodeficiency virus‐1 transactivator of transcription protein(TAT), respectively, facilitating the tumor‐cell‐membrane (with overexpressed α v β 3 integrin) and cell‐nucleus targeting. The formulated Ir‐RGD‐TAT (Ir‐R/T) NCs are demonstrated to accumulate inside the nucleus of tumor cells and generate effective DNA lesions upon X‐ray irradiation. Further in vivo evaluations verify the satisfactory carcinoma destruction performance against 4T1 tumor xenografts. Importantly, the intriguing photonic NIR adsorption of Ir‐R/T NCs has enabled the hyperthermia therapeutics accompanied with photoacoustic imaging modalities, achieving clinically promising biocompatible multifunctional radiosensitized nanoplatforms for effective tumor therapeutics.