Albumin-Based Cyanine Crizotinib Conjugate Nanoparticles for NIR-II Imaging-Guided Synergistic Chemophototherapy

Abstract

Colorectal cancer (CRC) is presently the third deadliest cancer in the world. This malignant cancer usually precedes the progression of precancerous lesions, and it is challenging to distinguish its nuanced morphological changes. Molecular-based near-infrared-II (NIR-II) fluorescence imaging can effectively recognize lesion targets to improve image contrast and increase early tumor detection compared with traditional wide-light screening endoscopy. c-Met has been determined to be overexpressed in advanced stages of CRC and is considered to be a potent tumor biomarker. Herein, based on the well-targeted inhibitory effect of Crizotinib on c-Met positive tumor cells, the dye IR808 was covalently combined with the drug molecule Crizotinib, resulting in the synthesis of a NIR fluorescent probe Crizotinib-IR808 targeting c-Met positive tumor cells. Then, water-insoluble Crizotinib-IR808 was fabricated by using bovine serum albumin (BSA) nanoparticles (NPs) with excellent biocompatibility and biosafety. The prepared Crizotinib-IR808@BSA NPs showed tumor targeting capability as well as use for noninvasive biomedical vascular NIR-II imaging with intraoperative real-time NIR-II imaging to guide tumor resection. Under 808 nm laser irradiation, Crizotinib-IR808@BSA NPs exhibited synergistic chemophototherapy effects on tumors. In conclusion, this innovative imaging-mediated multifunctional combination therapy strategy with good c-Met targeting ability may provide a new approach for colorectal cancer treatment.

An Asymmetric NIR-II Organic Fluorophore with an Ultra-Large Stokes Shift for Imaging-Guided and Targeted Phototherapy

“…TBy in DCM had a maximum absorption at 638 nm, and it was worth noting that the absorption band was fairly broad ranging from 430 to 800 nm. As shown in Figure S17, the relative fluorescence quantum yield (QY) of TBy was calculated to be 0.33% in dichloromethane (with reference to ICG with a QY of 1.6% in water) with a peak absorption coefficient of 3.23 × 10 4 M –1 cm –1 . Furthermore, the excellent photostability of TBy was confirmed.…”

Multifunctional Nanoplatform for NIR-II Imaging-Guided Synergistic Oncotherapy

“…However, the shorter emission wavelength may limit its application in deep tissues. Hu et al [71] covalently synthesized Crizotinib-IR808 with the clinically used drug Crizotinib and the NIR-II fluorescent dye IR808, with a unique structure that provides c-Met targeting ability, excellent 1 O 2 generation efficiency, and high photothermal conversion efficiency. Moreover, the optical stability and water solubility of the nanomaterials were significantly improved by the embedding of bovine serum albumin, which made it easier to specifically accumulate in colorectal cancer and allowed for a clearer differentiation of blood vessels, tumors, and peripheral boundaries by NIR-II imaging (Figure 2c-f).…”

“…(a) Schematic illustration of multifunctional phototherapeutic nanoplatform FE-T NPs for single 808 nm laser-triggered NIR-II imaging-guided mitochondrial-targeting antitumor therapy; (b) Real-time FLI of 4T1 tumor-bearing mice for FE NPs and FE-T NPs signals at 0.5, 2, 5, 8, 12, 24, and 48 h post-injection [32]. Copyright 2023, John Wiley and Sons; (c) NIR-II fluorescence images (150 ms, 1000 LP) of tumor-bearing mice at different time points after injection of Crizotinib-IR808@BSA; (d) Fluorescence intensity of tumor in the mice after administration of Crizotinib-IR808@BSA;(e) Semiquantitative analysis according to the fluorescence intensity in major organs and tumors after injection of Crizotinib-IR808@BSA; (f) Series images of the entire surgical process under NIR-II imaging 24 h after Crizotinib-IR808@BSA injection (150 ms, 1000 LP)[71]. Copyright 2023, American Chemical Society.…”

Nanoassemblies of heptamethine cyanine dye-initiated poly(amino acid) enhance ROS generation for effective antitumour phototherapy

“…For example, structural modifications of the dye backbone offered opportunities to enhance the photostability and improve the optical properties, 21,22 and developing carrier systems loading the dyes helped to ameliorate the pharmacokinetics. 23,24 However, altering the backbone structure has risks to diminish the intrinsic tumour-targeting ability of these dyes, since the structure–activity relationship of the tumour-targeting ability has not been clarified yet, 25 and encapsulating the dyes into delivery systems would mask the dye-mediated tumour-targeting. Thus, strategies that can improve the optical properties and pharmacokinetics without diminishing the inherent tumour targeting capability of heptamethine cyanine dyes are required.…”