Abstract:The flavonoid-based natural product genistein is a biologically active compound possessing promising anti-oxidant and anti-cancer properties. Poor pharmacokinetics along with low potency limit however the therapeutic application of genistein in cancer therapy. In order to overcome those limitations and to expand its therapeutic window of efficacy, we sought to covalently attach genistein with a heptamethine cyanine dye—IR 783—for cancer cell targeting and enhanced delivery to tumors. Herein we report the synth… Show more
“…It also exhibited cytotoxic synergism with TMZ, as co-treatment reduced the EC 50 by four-fold to 400 nM (71). Moderate toxicity has also been reported with IR-780 on the murine breast cancer 4T1 cell line (less than 30% reduction in cell viability with up to 16 mM), and IR-783 on the human MCF-7 breast cancer cell line (EC 50 of 25 mM) (58,87). Although cytotoxic activity is evident at supramicromolar concentrations, further studies are required to understand the structure-activity relationships across HMCDs.…”
“…Hence, the instantaneous reaction of HMCDs in serum is to form a non-covalent adduct with albumin. However, an ICG analogue synthesized by Tan and colleagues demonstrated high albumin binding affinity, resulting in an improved tissue accumulation and tumor selectivity through the EPR effect (58). The authors argue that the asymmetric properties of their dye, with a modified water-soluble carboxyl chain and liposoluble ester, are responsible for its ability to interact with and form complexes with albumin.…”
Section: The Role Of Albumin In the Uptake Of Hmcdsmentioning
confidence: 99%
“…The authors argue that the asymmetric properties of their dye, with a modified water-soluble carboxyl chain and liposoluble ester, are responsible for its ability to interact with and form complexes with albumin. Furthermore, the micropinocytosis inhibitor, amiloride, reportedly inhibited the uptake of the meso-Cl substituted genistein-IR-783 conjugate by 40% (58). Therefore, it is unclear whether the meso-Cl group would be required for the formation of albumin-complexes or the endocytosis of HMCDs into tumor cells.…”
Section: The Role Of Albumin In the Uptake Of Hmcdsmentioning
Effective cancer therapeutics for brain tumors must be able to cross the blood-brain barrier (BBB) to reach the tumor in adequate quantities and overcome the resistance conferred by the local tumor microenvironment. Clinically approved chemotherapeutic agents have been investigated for brain neoplasms, but despite their effectiveness in peripheral cancers, failed to show therapeutic success in brain tumors. This is largely due to their poor bioavailability and specificity towards brain tumors. A targeted delivery system might improve the efficacy of the candidate compounds by increasing the retention time in the tumor tissue, and minimizing the numerous side effects associated with the non-specific distribution of the chemotherapy agent. Heptamethine cyanine dyes (HMCDs) are a class of near-infrared fluorescence (NIRF) compounds that have recently emerged as promising agents for drug delivery. Initially explored for their use in imaging and monitoring neoplasms, their tumor-targeting properties have recently been investigated for their use as drug carrier systems. This review will explore the recent developments in the tumour-targeting properties of a specific group of NIRF cyanine dyes and the preclinical evidence for their potential as drug-delivery systems in the treatment of primary and metastatic brain tumors.
“…It also exhibited cytotoxic synergism with TMZ, as co-treatment reduced the EC 50 by four-fold to 400 nM (71). Moderate toxicity has also been reported with IR-780 on the murine breast cancer 4T1 cell line (less than 30% reduction in cell viability with up to 16 mM), and IR-783 on the human MCF-7 breast cancer cell line (EC 50 of 25 mM) (58,87). Although cytotoxic activity is evident at supramicromolar concentrations, further studies are required to understand the structure-activity relationships across HMCDs.…”
“…Hence, the instantaneous reaction of HMCDs in serum is to form a non-covalent adduct with albumin. However, an ICG analogue synthesized by Tan and colleagues demonstrated high albumin binding affinity, resulting in an improved tissue accumulation and tumor selectivity through the EPR effect (58). The authors argue that the asymmetric properties of their dye, with a modified water-soluble carboxyl chain and liposoluble ester, are responsible for its ability to interact with and form complexes with albumin.…”
Section: The Role Of Albumin In the Uptake Of Hmcdsmentioning
confidence: 99%
“…The authors argue that the asymmetric properties of their dye, with a modified water-soluble carboxyl chain and liposoluble ester, are responsible for its ability to interact with and form complexes with albumin. Furthermore, the micropinocytosis inhibitor, amiloride, reportedly inhibited the uptake of the meso-Cl substituted genistein-IR-783 conjugate by 40% (58). Therefore, it is unclear whether the meso-Cl group would be required for the formation of albumin-complexes or the endocytosis of HMCDs into tumor cells.…”
Section: The Role Of Albumin In the Uptake Of Hmcdsmentioning
Effective cancer therapeutics for brain tumors must be able to cross the blood-brain barrier (BBB) to reach the tumor in adequate quantities and overcome the resistance conferred by the local tumor microenvironment. Clinically approved chemotherapeutic agents have been investigated for brain neoplasms, but despite their effectiveness in peripheral cancers, failed to show therapeutic success in brain tumors. This is largely due to their poor bioavailability and specificity towards brain tumors. A targeted delivery system might improve the efficacy of the candidate compounds by increasing the retention time in the tumor tissue, and minimizing the numerous side effects associated with the non-specific distribution of the chemotherapy agent. Heptamethine cyanine dyes (HMCDs) are a class of near-infrared fluorescence (NIRF) compounds that have recently emerged as promising agents for drug delivery. Initially explored for their use in imaging and monitoring neoplasms, their tumor-targeting properties have recently been investigated for their use as drug carrier systems. This review will explore the recent developments in the tumour-targeting properties of a specific group of NIRF cyanine dyes and the preclinical evidence for their potential as drug-delivery systems in the treatment of primary and metastatic brain tumors.
“…In a similar approach, nitrogen mustard containing a phenolic hydroxyl group was conjugated to IR-808 ( 3 ) for tumor-targeting delivery [ 22 ]. On the other hand, the increased reactivity of phenolic hydroxyl group also allows direct conjugation with meso -Cl under intense conditions, e.g., the formation of genistein-IR783 conjugate ( 4 ) under NaH/DMF [ 23 ]. Fig.…”
Cyanine is a meritorious fluorogenic core for the construction of fluorescent probes and its phototherapeutic potential has been enthusiastically explored as well. Alternatively, the covalent conjugation of cyanine with other potent therapeutic agents not only boosts its therapeutic efficacy but also broadens its therapeutic modality. Herein, we summarize miscellaneous cyanine–therapeutic agent conjugates in cancer theranostics from literature published between 2014 and 2020. The application scenarios of such theranostic cyanine conjugates covered common cancer therapeutic modalities, including chemotherapy, phototherapy and targeted therapy. Besides, cyanine conjugates that serve as nanocarriers for drug delivery are introduced as well. In an additional section, we analyze the potential of these conjugates for clinical translation. Overall, this review is aimed to stimulate research interest in exploring unattempted therapeutic agents and novel conjugation strategies and hopefully, accelerate clinical translation in this field.
“…The design and build-up of organic-based chromophores exhibiting tailored electronic and optical features has become an active research field over the past decade. Among different applications, particular interest has been focused on optoelectronics (e.g., dye sensitized solar cells, photo- and chemical-switching systems, organic light emitting devices) [ 1 , 2 , 3 , 4 , 5 ], organic electronics, such as organic semiconductors [ 6 , 7 , 8 , 9 ], imaging technologies (e.g., electrophotography, thermal printing, and ink-jet printing) [ 10 ], and biomedicine (e.g., fluorescent sensors and anticancer treatments or photodynamic therapy) [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”
A new red hair-inspired 1,4-benzothiazine-based scaffold is disclosed herein, built upon a modular D-π-A architecture via condensation of the easily accessible 3-phenyl-2H-1,4-benzothiazine with indole-3-carboxaldehyde. The compound was obtained in around 50% yields and was characterized by complete spectroscopic analysis. The new benzothiazine-based cyanine displayed a characteristic reversible acidichromic behavior with a marked bathochromic shift upon acidification. The chromophore resisted at least fifteen hydrochloric acid/sodium hydroxide cycles without appreciable alterations. The expedient and scalable synthetic procedure together with the pH sensitive chromophoric properties would make the new compound an attractive prototype for novel modular chromophore for pH-sensing and other applications.
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