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Gene & Protein in Disease                                                    Cyanine and cancer therapy




            A                          B                       These species exhibit cytotoxicity with a short half-life and
                                                               low diffusion, ultimately leading to tumor cell apoptosis,
                                                               autophagy, and necrosis [227] .
                                                                 In a study by Zhang  et al., folate (FA) and Cy7-
                                                               modified chitosan (CF7) were chemically synthesized and
                                                               developed into self-assembled nanoparticles (CF7Ns) for
                                                               tumor-specific imaging and PDT. Experimental results
                                                               demonstrated that CF7Ns induced apoptosis in HeLa cells
                                                               on NIF light irradiation, thereby improving the therapeutic
            Figure  7. (A-B) Different small molecule cyanine compounds. These   [228]
            compounds can induce cancer cell apoptosis through PTT and PDT   efficacy  . CF7Ns show significant promise as tumor-
            combined therapy, thus exerting anti-tumor activity.  targeting agents [228] .
                                                                 Rizvi  et al. designed Cy5.5-coupled self-assembled
            caspase cascade reaction, leading to apoptosis of melanoma   peptide  nanoparticles  (f-SAPNs),  denoted  as  Cy5.5-
            cells. In addition, IR-817 induces G0/G1 cell cycle arrest   c RGD-KLAK . Their study revealed that Cy5.5-c could
                                                                [
                                                                          ]
            by targeting E2F/Cyclin/CDK signaling pathway without   produce ROS, disrupt mitochondrial membranes, activate
            causing apparent toxicity and side effects. Therefore, this   caspase-3 enzymes, and induce apoptosis in cancer cells [229] .
            mitochondrial-targeted therapeutic drug, IR-817, holds   PTT and photodynamic therapy primarily utilize
            promise for early diagnosis, real-time monitoring, and   NIR and nanoparticles, serving as photosensitive and
            drug treatment of tumors [224] .
                                                               photothermal agents. In PTT, gold nanoparticles produce
            5.2. Polymer nanoparticles                         heat upon activation by specific wavelengths of light,
                                                               effectively killing cancer cells. Similarly, PDT involves the
            5.2.1. Chemotherapy activity
                                                               production of ROS by gold nanoparticles to induce cancer
            Encapsulating chemotherapy drugs in nanoparticles can   cell death.
            reduce toxicity by enabling targeted delivery and controlled   Han  et al. developed Mito-Cy-Tfs, a mitochondrial-
            release [225] .
                                                               targeted fluorescence probe comprising three components:
              In a study by Zhang  et al., a novel tumor-targeting   (i)  NIF  heptamethine  cyanine  as  a  fluorescence  signal
            nanomedicine named AS1411-T-5-FU was developed to   converter; (ii) trifluoromethyl sulfonamide as a fluorescence
            enhance the therapeutic effectiveness against breast cancer.   regulator; and (iii) lipophilic triphenylphosphonium
            This nanomedicine incorporates Cy5, a fluorescent probe   cation as a mitochondrial guide. This cyanine derivative
            utilized for  labeling  DNA tetrahedrons, which improves   demonstrates apoptotic characteristics, such as alteration
            their photostability without compromising their essential   in the BAX/Bcl-2 ratio and the expression of Cyto C,
            function. AS1411-T-5-FU offers many advantages, such   cleaved-caspase-3, and cleaved-PARP [230] .
            as structural stability, biocompatibility, significant toxicity   Heptamethyl cyanine dye (HMCD) exhibits excellent
            to cancer cells, and the ability to selectively target cancer   tumor  specificity and  selectivity, capable of  inducing
            cells. The mechanism of action of AS1411-T-5-FU involves
            inducing mitochondrial apoptosis, highlighting its   apoptosis through mitochondrial damage, making it a
                                                                                                    [231]
            potential as a promising novel anti-cancer drug with potent   promising candidate for treating brain tumors  . HMCD
            efficacy and selective toxicity on breast cancer cells [226] .  dyes are used for imaging due to their optimal NIF emission
                                                               and excellent photophysical properties. Furthermore, they
            5.2.2. Photothermal activity                       hold potential as effective drug carriers for brain tumor
                                                               treatment (Figure 8).
            Nanoparticle-based phototherapies, such as PTT and PDT,
            represent promising approaches for tumor eradication.   HA-PEG-CyI (HPC) is novel therapeutic nano-carriers
            These therapies not only directly target undetectable   developed by Chi et al. Under 808 nm laser irradiation, HPC
            tumors and metastatic cancers but also hold the potential   can produce ROS and elevate the temperature, triggering
            for treating other conditions, such as melanoma, and   apoptosis and necrosis at the tumor site. HPC-induced cell
            overcoming drug resistance. In addition, they can activate   death may initiate a range of acute inflammatory reactions,
            systemic immune responses by modulating the tumor   resulting in  systemic  immune  induction and secondary
            microenvironment [227] .                           death of tumor cells, further reducing tumor recurrence [232] .
              Photodynamic therapy exerts its anti-tumor effect by   Yu et al. developed nano-ethanol loaded with IR-808
            generating ROS and free radicals through interactions   (IR-808-ES) as a novel nanoparticle-based photosensitizer
            with the plasma nano-platform of the local electric field.   for transdermal PDT/PTT of hypertrophic scars (HS).

            Volume 2 Issue 4 (2023)                         11                       https://doi.org/10.36922/gpd.2486
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