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Gene & Protein in Disease Cyanine and cancer therapy

ends or in the middle of the conjugated chain. Cyanines subsequently induces apoptosis or cell cycle arrest in
exhibit excellent properties, such as fluorescence features, cancer cells.
including high molar absorbance, narrow absorption
and emission bands, and compatibility with UV/VIS and 5.1.1. Chemotherapy activity
near-infrared (NIR) regions [185-187] . Common cyanine dyes Chemotherapy stands out as a significant approach in
used for biomolecule labeling, such as DNA and proteins, cancer treatment, and small molecule cyanine derivatives
include Cy3 (Figure 4A), Cy5 (Figure 4B), and Cy7 can contribute to this therapeutic strategy. Mitochondria,
(Figure 4C). These dyes can induce apoptosis in cancer cells being pivotal subcellular organelles, serve as crucial targets
by producing ROS or high temperatures, thereby exerting for drug delivery, exerting a crucial effect in apoptosis.
an anti-tumor effect. Cyanine structures find widespread Therefore, inducing apoptosis through mitochondrial
applications and can contribute to the anti-tumor effect by damage presents a viable avenue for tumor treatment.
inducing apoptosis in cancer cells.
Cyanine chromophores (Cy7-Cl), a derivative of
Photosensitive therapy presents a promising approach heptamethine cyanine dyes developed and synthesized
for tumor treatment, including photodynamic therapy by our research groups, demonstrate anti-tumor effects
(PDT) and PTT [188] . PDT, in particular, is a highly effective through its chemotherapy activity (Figure 5A). On
cancer treatment strategy due to its minimally invasive localization to mitochondria, Cy7-Cl induces mitochondrial
nature, effective targeted destruction of tumor cells, and the dysfunction, influencing the expression of BAX and Bcl-2
significant induction of systemic anti-tumor immunity [189] . through AMPK signaling. This process leads to a reduction
This innovative method utilizes photosensitive drugs in mitochondrial membrane potential and ATP content.
in combination with laser activation to target tumors. Furthermore, Cy7-Cl affects the release of free Cyt C from
Photosensitizing drugs deliver energy to ambient oxygen, mitochondria to the cytoplasm, thereby increasing ROS
leading to the production of ROS, which exert toxicity and content and stimulating the activity of cleaved-caspase 3,
induce cell death [190] . Compared to traditional therapy, ultimately inducing apoptosis in CRC cells.
PDT offers advantages such as enhanced targeting, effective Mitochondria are central organelles in the intrinsic
treatment outcomes, and reduced side effects [191,192] . apoptosis pathway of 2,2’- and 4,4’- cyanines (Figure 5B).
Notably, PDT-induced apoptosis has been reported to Kadigamuwa et al. have demonstrated that these compounds
release signaling molecules that trigger immune cell death, can accumulate in mitochondria at high concentrations,
which is crucial for combating metastatic tumors and resulting in mitochondrial membrane depolarization, ROS
preventing recurrence [193] .
production, and apoptosis of cancer cells [194] .
5.1. Small molecule cyanine derivatives Yang et al. found that D112 (Figure 5C) induces
Small molecule cyanine derivatives play an essential role caspase activation, mitochondrial depolarization,
in tumor therapy. They can exert an anti-tumor effect phosphatidylserine externalization, and Cyto C release,
by accumulating within mitochondria, leading to the consequently activating caspase-9 and eventually
depolarization of the mitochondrial membrane. This inducing cell apoptosis. High doses of D112 trigger the
accumulation triggers the production of ROS, which mitochondrial apoptosis pathway, while low doses induce
apoptosis and cell cycle arrest dependent on mitochondrial
dysfunction. These results suggest that D112 is a potential
A B
small molecule warranting further investigation [195] .
Patil et al. synthesized cyanine-based 3-methoxy pyrrole
and other cyanine derivatives, including 7n (Figure 5D)
and 7p (Figure 5E), which localize to the mitochondria
of HeLa cells and induce cell damage. These small
C molecules interfere with anti-apoptosis (Bcl-2/Bcl-xl) and
pro-apoptosis (BAX) proteins, produce ROS, arrest the
cell cycle in the G0/G1 phase, activate caspase-3/9, and
ultimately induce apoptosis of cervical cancer cells .
[46]
Chitooligosaccharides (COS) found in shrimp and crab
shells exhibit promising anti-tumor activity and hold potential
Figure 4. (A-C) Cyanine derivatives with different chain lengths. They are as adjuvant therapy alongside other chemotherapy drugs [196] .
essential in tumor treatment and labeling. COS-Cy7, synthesized by Zhai et al., has demonstrated

Volume 2 Issue 4 (2023) 8 https://doi.org/10.36922/gpd.2486