Increasing Photothermal Efficacy by Simultaneous Intra‐ and Intermolecular Fluorescence Quenching

Abstract

Recently, using in situ self-assembly-induced fluorescence quenching (i.e., intermolecular quenching denoted herein) of a photothermal agent (PTA) to enhance its photothermal efficiency has proven to be a successful photothermal therapy (PTT) strategy. But to the best of current knowledge, using simultaneous intra-and intermolecular fluorescence quenching of a PTA to additionally increase its photothermal efficacy has not been reported. Herein, employing a click condensation reaction and a rationally designed PTA Biotin-Cystamine-Cys-Lys(Cypate)-CBT (1), a "smart" strategy is developed of intracellular simultaneous intra-and intermolecular fluorescence quenching and applied it to largely increase the photothermal efficacy of the agent both in vitro and in vivo. After being internalized by biotin receptor-overexpressing cancer cells, 1 is reduced by intracellular glutathione to initiate a CBT-Cys condensation reaction (intramolecular quenching) and self-assembly (intermolecular quenching) to form the nanoparticles 1-NPs (simultaneous intra-and intermolecular fluorescence quenching). Experimental results indicate that 1-NPs have higher fluorescence quenching efficiency than the control PTAs [Thiazole-Lys(Cypate)-Benzothiazole] 2 (1-Dimer, intramolecular quenching), and nanoparticles of Cystamine-Cys(Fmoc)-Lys(Cypate)-CBT (1-Fmoc-NPs, intermolecular quenching). It is envisioned that, by replacing the biotin group on 1 with other targeting warheads, the "smart" strategy is ready to increase the photothermal therapeutic efficiency of their corresponding diseases.

Recent advances in selective photothermal therapy of tumor

“…The concentration difference between normal tissue and tumor tissue can be generated, and the temperature of the tumor site can be selectively increased [ 15 ]. The ideal solution is to give PTAs a self-regulating photothermal conversion capability, which means that PTAs have a weak photothermal conversion ability in normal tissue but a strong photothermal conversion ability at the tumor site [ 13 , 14 , 16 ]. Theoretically, the temperature of the tumor site can be selectively increased, with minimal or no damage to normal cells.…”

Furin‐Instructed Intracellular Gold Nanoparticle Aggregation for Tumor Photothermal Therapy

“…Next, we checked the photothermal conversion efficiency (η) of AuNP@1 + GSH + Furin, AuNP@1‐Scr + GSH + Furin, and AuNP by measuring their heating and cooling curves using previously reported methods (Figure S21, Supporting Information). [ 31 ] The calculated η value of AuNP@1 + GSH + Furin was 3.02%, higher than those of both AuNP@1‐Scr + GSH + Furin (η = 2.99%) and AuNP (η = 1.39%). Above results well confirmed that furin‐instructed aggregation of AuNP@1 enhanced the photothermal properties of gold nanoparticles.…”

Biological functions of supramolecular assemblies of small molecules in the cellular environment

“…Moreover, SASMs, being generated by a specific enzymatic reaction, are also able to interact with multiple targets or to disrupt multiple pathways in cancer cells, 43 which makes SASMs attractive molecular entities for killing cancer cells effectively, reducing side effects, and minimizing MDR in cancer therapy. 44,45 …”