Stable intermolecular charge-transfer nanocrystals as efficient immunogenic cell death adjuvants for photoimmunotherapy against trophoblastic and recurrent tumors

Organic photothermal agents (PTAs) with high-performance near-infrared properties hold great promise for precision phototherapy and bioimaging. The development of efficient PTAs depends mainly on advancements in molecular synthesis. However, synthetic approaches for organic PTAs typically involve tedious processes and the consumption of noble metal catalysts, which could leave residues affecting the products' biosafety. In the past few years, a handful of charge transfer complex (CTC) PTAs have been reported. Unfortunately, typical CTCs disintegrate into their donor and acceptor components in water because of their stronger hydrogen bonds with water. To address this issue, facile and synthesis-free super-stable interfacial charge-transfer nanocrystals (H-CTC NPs) have been reported for increasing immunogenic cell death and efficient photoimmunotherapy against tumor recurrence. Water-dispersible H-CTC NPs between pyrene-4,5,9,10-tetrone (PT, acceptor) and indolo[2,3-alpha]carbazole (IC, donor) were prepared with strong intermolecular hydrogen bonds. With this approach, H-CTC NPs are the first examples of stable CTC NPs in water, achieving record-high stability with preferable photothermal conversion efficiency. H-CTC NPs typically cause immunogenic cell death (ICD) and photothermal tumor ablation in vivo. Moreover, distal recurrent tumors are inhibited through the immune synergism between ICD and immune checkpoint therapy. This work developed superstable CTC nanocrystals and explored new pathways for high-performance photoimmunotherapy against recurrent tumors.

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