Reactive Glycolysis Metabolite‐Activatable Nanotheranostics for NIR‐II Fluorescence Imaging‐Guided Phototherapy of Cancer

Abstract

Second near‐infrared (NIR‐II) fluorescence imaging with deep tissue‐penetration ability holds remarkable potential for cancer diagnosis. However, clinical translation of NIR‐II fluorescence imaging‐based cancer treatment is severely restricted by the low signal‐to‐background ratio due to insufficient tumor specificity of fluorophores. In this study, it is hypothesized that methylglyoxal (MGO), an intermediate metabolite of tumor glycolysis could be used as a potent biomarker for triggering NIR‐II fluorescence imaging‐guided cancer theranostic. For proof‐of‐concept, first a MGO‐activatable NIR‐II fluorescence probe is developed, and then MGO‐responsive “dual lock‐and‐key” nanotheranostics by integrating the NIR‐II fluorophore and a photodynamic prodrug (i.e., hexyl 5‐aminolevulinic acid hydrochloride (HAL)) into one nanoparticle is engineered. The nanotheranostic can be specifically activated with tumorous MGO for NIR‐II fluorescence imaging‐guided combinatory cancer therapy. Upon 808 nm laser irradiation, the activated NIR‐II fluorophore can generate tunable photothermal effect to trigger HAL release. Subsequently, HAL is converted to protoporphyrin IX inside the tumor cells for 655 nm laser irradiation‐induced photodynamic therapy. It is demonstrated that the NIR‐II fluorescence nanotheranostics is highly specifically activated in the tumor and efficiently suppressed 4T1 breast tumor growth in mouse model. The NIR‐II fluorescence imaging‐based nanotheranostic might imply novel insight into reactive metabolite‐activatable precise therapy of tumor.

Self-Assembly of Small Organic Molecules into Luminophores for Cancer Theranostic Applications

“…Under the NIR-II laser irradiation, this strategy achieved NIR-II fluorescence/photoacoustic dual-modal imaging-guided photothermal therapy (PTT) and photonic thermodynamic therapy (PTDT), enabling precise diagnosis and effective suppression of tumors with negligible side effects. In a recent study, Xu and coworkers designed a methylglyoxal (MGO)-activatable NIR-II fluorescence probe, which was co-encapsulated with an endogenous photodynamic prodrug into lipid nanoplatforms for NIR-II fluorescence imaging-guided cancer phototheranostics ( Figure 4 c,d) [ 74 ]. Under different light conditions, it activated fluorescence imaging and targeted mitochondria to produce ROS.…”

“…Copyright 2021 John Wiley and Sons. Adapted with permission from [ 74 ]. Copyright 2022 John Wiley and Sons.…”

Phase-change materials-based platforms for biomedicine

“…These hydrophobic TRIDENT PCMs encapsulated with a broad-spectrum antibiotic (imipenem, IMP) and IR780 and subsequently coated with lecithin and DSPE-PEG 2000 not only resulted in the NIR-assisted melting of the nanotransporter but also damaged the membrane facilitating the permeation, as well as interfering in the cell wall biosynthesis and enable bacterial death (Figure 2C) (Qing et al, 2019). In this regard, several PCMs-based on LA and SA, as well as oleic acid, were fabricated for nanotheranostics with the ability of hyperthermia-triggered spatiotemporally tunable drug release (Cai et al, 2021;Lai et al, 2022).…”

Dual-targeting prodrug nanotheranostics for NIR-Ⅱ fluorescence imaging-guided photo-immunotherapy of glioblastoma

“…Phototherapy, in particular, photothermal therapy (PTT) has been demonstrated to ablate the tumor cells by inducing hyperthermia effect 22 , 23 , 24 . For instance, inorganic nanomaterials or organic molecules with photo-absorbance in the near-infrared (NIR) window have been investigated for PTT in vitro and in vivo 25 , 26 , 27 , 28 , 29 . Apart from photothermal ablation of the tumor cells, PTT has recently been demonstrated to elicit antitumor immunity by releasing antigen at the tumor site and recruiting the tumor-infiltrating CTLs 30 .…”