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Gene & Protein in Disease Photothermal therapy of pentamethine cyanine

CRC incidence rate and mortality rate are among the top was the only contrast medium authorized by the U.S. Food
three in the world . Surgical treatment, radiotherapy, and and Drug Administration. Therefore, the development of
[3]
chemotherapy are the principal clinical treatment methods new photosensitizers based on the intrinsic multifunctional
of CRC . However, the common chemotherapeutic drugs, characteristics of their chemical structure, which do not
[4]
such as fluorouracil and oxaliplatin, have predictable rely on nanopolymer materials and do not need complex
hepatotoxicity [5,6] . Therefore, it is urgent to develop an chemical connections, significantly improved the potential
effective and low-toxicity drug for CRC treatment. of clinical transformation and application, and promoted
The combination of advanced optical technology and the prospects of tumor optical therapy.
tumor treatment provides non-invasive in vivo imaging In the present study, recognizing the potential of cyanine
and treatment (optical diagnosis and therapy) employing fluorophore, a unique water-soluble pentamethine cyanine-
non-ionizing radiation, which brings new understanding derivative, 1-(4-carboxybenzyl)-2,3,3-trimethylindoleninium-
and technological innovation to biomedicine, and is 5-sulfonate bromide (CY5-664), was designed and synthesized
expected to achieve precise treatment of tumors [7,8] . to investigate the photosensitive activity and to explore its
Tumor phototherapy is a method of treating cancer with potential applications as NIR photosensitizer for CRC
specific wavelength excitation photosensitizer, including diagnosis and therapy. An excellent molar extinction
photothermal therapy (PTT) and photodynamic therapy coefficient, a relatively higher quantum yield, and good
(PDT) [9,10] . PTT, based on the theory concerning the photostability are exhibited in CY5-664 aqueous solutions.
absorbed light for heat conversion, has tremendous CY5-664 inhibits cell viability and exhibits excellent PTT
potential for efficacious cancer therapy, compared activity in two types of CRC cell lines in a dose-dependent
with traditional treatment modalities such as surgery, manner under NIR laser irradiation. Moreover, it is retained
radiation therapy, and chemical therapy, due to the non- preferentially in tumors and significantly inhibits tumor
invasive therapeutic intervention and precise spatial- growth in the BALB/c nude mice xenografts bearing
temporal selectivity [11,12] . PDT is another new strategy DLD-1 cells under NIR laser irradiation with negligible
for cancer therapy, accompanied by photosensitizers and organ toxicity. Therefore, for the 1 time, we found the novel
st
laser activation. The laser energy is transferred to the small molecular derivative of cyanine CY5-664 against CRC,
surrounding oxygen by photosensitizer and highly active which may be high efficiency and low-toxicity PTT material
singlet oxygen is produced to kill cancer cells . However, for image-guided CRC therapy in clinical application.
[13]
the low oxygen content of the tumor microenvironment
limits the extensive application of oxygen-dependent 2. Materials and methods
PDT . Compared with oxygen-dependent PDT, PTT is
[14]
oxygen-independent and, therefore, may serve as a more 2.1. Chemicals and reagents
promising cancer therapy approach. PTT photosensitizer CY5-664 was synthesized according to the predetermined
effectively converts the laser energy into thermal energy synthetic route, and the synthetic routes were shown in
through absorbing energy in the near-infrared (NIR) Figure 1A. H NMR spectra were recorded on a Bruker
1
region and taking advantage of the sensitivity of cancer AMX-400 spectrometer (400 MHz; Bruker, U.S.A.).
cells toward heat to induce hyperthermia and promote Mass spectral analysis was performed using an MALDI-
cancer cell necrosis and apoptosis [15,16] . TOF mass spectrometer (Applied Biosystems/MDS Sciex,
Tremendous efforts have been made to obtain high Foster City, CA, U.S.A.). Fluorescence measurement was
efficiency and low-toxicity PTT materials. Although a performed using a Cary Eclipse spectrofluorimeter (Agilent
large number of polymeric and inorganic nanomaterials Technologies, U.S.A.) with 5 nm excitation and emission
have been studied in the application of PTT, such as slit widths. Absorption spectra were measured using a Jasco
gold nanoparticles , metal sulfide nanoparticles , V-550 spectrophotometer (JASCO International Co., Japan).
[18]
[17]
and carbon nanomaterials , there are still tremendous All reagents used for the experiments were of analytical
[19]
challenges to clinically apply these PTT materials due to the grade. HSP70 and β-actin antibodies were purchased from
complex synthetic process, the raised concerns regarding Servicebio Co. Ltd. (Wuhan, China). MTT assay kit was
biocompatibility, and the unsolved biosafety problem [16,20] . purchased from Solarbio Co. Ltd. (Beijing, China). Singlet
In contrast, NIR heptamethine cyanine fluorophore such oxygen sensor green (SOSG) detection kit was purchased
as indocyanine green (ICG) recently received increasing from Maokangbio Co. Ltd. (Shanghai, China).
attention in PTT because of excellent biocompatibility, 2.2. Cell lines and cell culture
non-immunogenicity, high fluorescence and photothermal
conversion efficiency, photostability, tumor-homing, and As previously described , human CRC cell lines such as
[23]
commercial-scale production [11,21,22] . Up to the present, ICG HCT-116 and SW480 were obtained from the cell culture

Volume 1 Issue 1 (2022) 2 https://doi.org/10.36922/gpd.v1i1.87