Medical Applications and Advancement of Near Infrared Photosensitive Indocyanine Green Molecules

Abstract

Indocyanine green (ICG) is an important kind of near infrared (NIR) photosensitive molecules for PTT/PDT therapy as well as imaging. When exposed to NIR light, ICG can produce reactive oxygen species (ROS), which can kill cancer cells and pathogenic bacteria. Moreover, the absorbed light can also be converted into heat by ICG molecules to eliminate cancer cells. In addition, it performs exceptionally well in optical imaging-guided tumor therapy and antimicrobial therapy due to its deeper tissue penetration and low photobleaching properties in the near-infrared region compared to other dyes. In order to solve the problems of water and optical stability and multi-function problem of ICG molecules, composite nanomaterials based on ICG have been designed and widely used, especially in the fields of tumors and sterilization. So far, ICG molecules and their composite materials have become one of the most famous infrared sensitive materials. However, there have been no corresponding review articles focused on ICG molecules. In this review, the molecular structure and properties of ICG, composite material design, and near-infrared light- triggered anti-tumor, and antibacterial, and clinical applications are reviewed in detail, which of great significance for related research.

Keywords: ICG; antibacterial treatment; composite nanoparticles; light therapy; tumor treatment.

Figure 3

(A) Schematic of ZSZIT nanosystem with high loading ICG for combined H₂S amplified phototherapy/chemotherapy [14]. (B) Nanoplatform with big cavity and porous network structure for optimal phototherapy/chemotherapy synergy and high drug loading [15]. (C) Schematic illustrating the synergistic use of the cancer cell membrane-encapsulated bionic agent DIHPm16 and DOX/ICG co-delivery [16]. (D) Nanoplatform (ICG-PtMGs@HGd) that targets tumor hypoxia limitation in order to improve ICG photodynamics and cause cell death [18]. (E) Nanoplatform carrying GOX/Metal Polyphenol Network (MPN) for continuous oxygen generation and alteration of bacterial infection site PH to enhance synergistic phototherapeutic/chemodynamic effects involving ICG [19]. (F) PDT/PTT combination therapy with Fe-DOX@Gd-MOF-ICG [20].

Figure 4

(A,B) Connecting ICG’s micelles [24,26]. (C) Assembly of ICG and PEG-PLL-PLLeu [28].

Figure 5

(A) Ocular detection and treatment using the photothermal/fluorescent/photoacoustic imaging capabilities of the FDA-approved contrast agent ICG [29]. (B) Oxygen-carrying capacity of perfluorooctane bromide enhances aPDT treatment with PA/FL imaging lead-in [30]. (C) Liposome-encapsulated ultra-bright fluorophores display 38.7 times brighter NIR-II than free ICG and last up to 30 min for cerebrovascular imaging [32]. (D) ICG, DOX, and conjugated gadolinium chelates are released synergistically as a result of photothermal stimulation of thermosensitive liposomal phase transition [33]. (E) ICG transmits energy to activate Ce6, which then consumes oxygen and creates a hypoxic state that triggers the anticancer medication TPZ action [34]. (F) Novel nanoparticles consisting of thermosensitive liposomes, ICG and CuS NPs [35].

Figure 9

(A) A dual anti-tumor pathway nanosystem in which ROS damage the endoplasmic reticulum and induce a large release of calcium ions from the endoplasmic reticulum to stimulate other subcellular organelles such as mitochondria [31]. (B) Single phototherapy session in NIR by combining two photosensitizers [59]. (C) ICG-derived fluorophores excreted by the renal tubules [60]. (D) Schematic diagram of phototherapy after arrangement of ICG molecules into J-aggregates [63]. (E) Schematic diagram of the formation of biocompatible ICGNiosomes (ICGNios) that keep ICG molecules from being degraded in thicker tissues while maintaining strong fluorescence intensity [66]. (F) Schematic of the construction of a new PA contrast agent using ICG [67].

Figure 10

(A) Gold nanosystems for periodontitis and bacterial biofilms carrying ICG and nitrogen oxides [77]. (B,C) Upconversion nanosystem for dual gas therapy to modulate inflammation and enhance the photodynamic effect of ICG [78]. (D) Antimicrobial system of ICG-generated ROS disrupts bacterial membranes allowing gallium to penetrate the membrane causing disorders of iron metabolism [83]. (E) Therapeutic system for generating high-heat MoS₂ nanosheets loaded with photothermal agents and antimicrobial Ag⁺ [84]. (F) Schematic of glutathione-depleting and hyperthermia-damaging biofilm [85].

Figure 1

ICG Nanocomposite and its Applications.

Figure 2

Chemical structure of ICG [4].

Figure 6

(A) Acid and GSH degradation release DOX and ICG from polymeric micelles [36]. (B) ICG covalently bound high loading micelles [37]. (C) ICG-bound and GA-loaded polymeric micelles for local chemotherapy–photothermal synergistic therapy of breast cancer [38]. (D) Mechanism of PPH@5Fu@ICG for GC [39]. (E) Preparation of ICG-HA-PTX and imaging-guided photothermal effect [40]. (F) Synthesis and structure of ITM [41].

Figure 7

(A) Bioimaging-guided interventional photothermal therapy [44]. (B) Anti-tumor diagram of TNYL-ICG-HAuNS [45]. (C) PNMAuDIs treatment for breast cancer metastasis [46]. (D) Nanomaterials MLI-AuNCs for inhibiting recurrence of aggressive melanoma. inhibit melanoma-associated antigens, resulting in the inhibition of DC maturation and IFN-γ, and thus inhibit the recurrence of aggressive melanoma [47]. (E) Preparation of DOX/ICG@Biotin-PEG-AuNC-PCM for chemotherapy/photodynamic therapy [48]. (F) Gold-nano bipyramidal nanootheranostics for imaging and phototherapy [49].

Figure 8

(A,B) Nanosystem consisting of a calcium carbonate carrier as a delivery ICG [52,53]. (C) Combination therapy system of MnO₂-assisted ICG to enhance photodynamic effect and suppression of immune checkpoint PD-L1 by siRNA [54]. (D) Nanoplatform for apoptosis induced by thermal effects and cytotoxicity generated by ICG molecules and drug activity of tumor-associated macrophages [55].

Figure 11

Near-infrared fluorescence imaging of healthy and affected limbs [86].