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

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 αv β3 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 αv β3 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.