Emerging indocyanine green-integrated nanocarriers for multimodal cancer therapy: a review

Abstract

Nanotechnology is a branch of science dealing with the development of new types of nanomaterials by several methods. In the biomedical field, nanotechnology is widely used in the form of nanotherapeutics. Therefore, the current biomedical research pays much attention to nanotechnology for the development of efficient cancer treatment. Indocyanine green (ICG) is a near-infrared tricarbocyanine dye approved by the Food and Drug Administration (FDA) for human clinical use. ICG is a biologically safe photosensitizer and it can kill tumor cells by producing singlet oxygen species and photothermal heat upon NIR irradiation. ICG has some limitations such as easy aggregation, rapid aqueous degradation, and a short half-life. To address these limitations, ICG is further formulated with nanoparticles. Therefore, ICG is integrated with organic nanomaterials (polymers, micelles, liposomes, dendrimers and protein), inorganic nanomaterials (magnetic, gold, mesoporous, calcium, and LDH based), and hybrid nanomaterials. The combination of ICG with nanomaterials provides highly efficient therapeutic effects. Nowadays, ICG is used for various biomedical applications, especially in cancer therapeutics. In this review, we mainly focus on ICG-based combined cancer nanotherapeutics for advanced cancer treatment.

Fig. 1. Schematic illustration of ICG-based organic, inorganic, and hybrid nanocarriers.

Fig. 2. EPR: (A) passive targeting of nanoparticles, (B) active targeting of nanoparticles, and (C) triggered release of nanoparticles under tumor microenvironment conditions.

Fig. 3. (a) Schematic representation of trimodal therapy, PDT/PTT/chemotherapy, in a human breast cancer model. Reproduced with permission from ref. . Copyright 2018, Elsevier. (b) Design and function of the dual-targeted phototherapy agent indocyanine green. Reproduced with permission from ref. . Copyright 2016, American Chemical Society.

Fig. 4. (a) Schematic illustration of theranostic micelles for prolonged cancer imaging and photothermal therapy with carbocyanine dyes. Reproduced with permission from ref. . Copyright 2013, Elsevier. (b) Schematic illustration of pH-sensitive loaded retinal/ICG micelles as an all-in-one theranostic agent for multimodal imaging. Reproduced with permission from ref. . Copyright 2019, Royal Society of Chemistry.

Fig. 5. (a) Schematic illustration of DI-NGs@lipo prepared by in situ polymerization within a liposome template. (b) NIR-induced hyperthermia triggered intracellular DOX release for synergistic chemo-photothermal therapy. Reproduced with permission from ref. . Copyright 2018, American Chemical Society. (c) Self-assembly process of the ICG–PL–PEG probe. (d) Targeted modification of the ICG–PL–PEG probe. Reproduced with permission from ref. . Copyright 2011, American Chemical Society.

Fig. 6. (a) Schematic illustration of sonochemotherapy using HA-modified nanocomposites. Reproduced with permission from ref. . Copyright 2019, Royal Society of Chemistry. (b) Schematic illustration of nanogel fabrication from PPEGMA-co-PHPMA-co-PADMA copolymers and PAMAM–CD dendrimers. Reproduced with permission from ref. . Copyright 2015, Royal Society of Chemistry.

Fig. 7. Schematic illustration of (A) preparation of DOX&ICG@BSA-KALA/Apt nanoparticles and (B) the theranostic process based on DOX&ICG@BSA-KALA/Apt nanoparticles. Reproduced with permission from ref. . Copyright 2019, American Chemical Society. (C) Schematic illustration showing the outline of preparation of ICG-SF nanoparticles by the SAS process and dual-triggered cancer therapeutics. Reproduced with permission from ref. . Copyright 2018, American Chemical Society.

Fig. 8. (a) A schematic illustration of SPIO@DSPE-PEG/ICG NP preparation. (b) UV absorbance after treatment with different concentrations of SPIO@DSPE-PEG/ICG NPs with or without NIR laser irradiation. (c and d) TEM images of NPs. (e and f) Size distribution pattern of NPs. Reproduced with permission from ref. . Copyright 2013, Elsevier.

Fig. 9. (a) Schematic illustration of synthesis and function of gold nanoparticles with encapsulated ICG. Reproduced with permission from ref. . Copyright 2014, American Chemical Society. (b and c) Schematic of the synthesis and application of PS@CS@Au–Fe₃O₄–FA/ICG. Reproduced with permission from ref. . Copyright 2017, Royal Society of Chemistry.

Fig. 10. Preparation of (a) PLL–ICG/DPEG and (b) PLL–ICG/SPEG NPs using the MS templating method for PTT and PDT. (c) Cell viability in the presence of ICG, PLL–ICG/DPEG NPs, and PLL–ICG/SPEG NPs with NIR laser irradiation. (d) Comparison of PDT, PTT, and simultaneous PDT/PTT effects on cell viability. Reproduced with permission from ref. . Copyright 2019, American Chemical Society. (e) Schematic illustration of the DOX&ICG@MSN-T@poly A design, triggered drug release, anticancer process, and immunity activation mechanism. Reproduced with permission from ref. . Copyright 2019, American Chemical Society.

Fig. 11. (a) Synthetic route used to prepare PLC-ZD55-IL-24 and graphical representation of tumor volume increase without NIR irradiation. Reproduced with permission from ref. . Copyright 2016, American Chemical Society. (b) Schematic illustration of PhotoImmunoNanoTherapy utilizing ICG–CPSNP–PEG, which exerts an antitumor effect by generating dihydrosphingosine-1-phosphate (dhS1P). Reproduced with permission from ref. . Copyright 2013, American Chemical Society.

Fig. 12. Schematic representation of a multifunctional IDCB–LDH nanomedicine. (a) The hybrid nanomedicine is constructed by first coating with BSA and then orderly loading ICG, DOX/DNA prodrug, and C_PG ODN 1826. (b) IDCB–LDH with 808 nm NIR irradiation heats the tumor tissues and releases DOX at a temperature above 41 °C to kill tumor cells through efficient PTT. (c) Mature DCs activate naïve T cells in dLNs and induce potent CTLs. Reproduced with permission from ref. . Copyright 2019, American Chemical Society.

Fig. 13. Schematic illustration of the synthesis of Fe₃O₄@PLGA–PVP core–shell NCs for HER2 targeted endocytosis and breast cancer application of the nanocomposite. Reproduced with permission from ref. . Copyright 2016, American Chemical Society. (b) Schematic illustration and preparation of gadolinium oxide–gold nanocluster nanohybrids for multi-modal imaging therapy. Reproduced with permission from ref. . Copyright 2017, American Chemical Society. (c) Schematic illustration of the ICG–Au@BSA–Gd theranostic agent for PTT and PDT effects for cancer therapy. Reproduced with permission from ref. . Copyright 2017, American Chemical Society.

Karunanidhi Gowsalya

Vellingiri Yasothamani

Raju Vivek