Theranostic system for ratiometric fluorescence monitoring of peptide-guided targeted drug delivery

Rozovsky, Alex; Ebaston, T. M.; Zaporozhets, Alisa; Bazylevich, Andrii; Patsenker, L. D.; Gellerman, Gary

doi:10.1039/c9ra06334j

Cited by 11 publications

(8 citation statements)

References 45 publications

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“…In this type of PDCs, the drug is attached to the carrier through a "switchable" fluorescent dye that changes its emission wavelength upon drug cleavage. Such design of drug-fluorophore PDC enables ratiometric monitoring of cytotoxic cargo release in the body during treatment (Figure 9) [213][214][215]. Another interesting approach for conjugation drug therapy involves direct fusion of two drugs into a single molecule.…”

Section: Combining Through Conjugation-implementing Antibodies Peptides and Chimeric Moleculesmentioning

confidence: 99%

Drug Combination in Cancer Treatment—From Cocktails to Conjugated Combinations

Gilad

Gellerman

Lonard

et al. 2021

Cancers

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It is well recognized today that anticancer drugs often are most effective when used in combination. However, the establishment of chemotherapy as key modality in clinical oncology began with sporadic discoveries of chemicals that showed antiproliferative properties and which as a first attempt were used as single agents. In this review we describe the development of chemotherapy from its origins as a single drug treatment with cytotoxic agents to polydrug therapy that includes targeted drugs. We discuss the limitations of the first chemotherapeutic drugs as a motivation for the establishment of combined drug treatment as standard practice in spite of concerns about frequent severe, dose limiting toxicities. Next, we introduce the development of targeted treatment as a concept for advancement within the broader field of small-molecule drug combination therapy in cancer and its accelerating progress that was boosted by recent scientific and technological progresses. Finally, we describe an alternative strategy of drug combinations using drug-conjugates for selective delivery of cytotoxic drugs to tumor cells that potentiates future improvement of drug combinations in cancer treatment. Overall, in this review we outline the development of chemotherapy from a pharmacological perspective, from its early stages to modern concepts of using targeted therapies for combinational treatment.

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Section: Combining Through Conjugation-implementing Antibodies Peptides and Chimeric Moleculesmentioning

confidence: 99%

Drug Combination in Cancer Treatment—From Cocktails to Conjugated Combinations

Gilad

Gellerman

Lonard

et al. 2021

Cancers

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“…Conjugates 13a–b displayed a noticeable enhancement in ﬂuorescence quantum yield but changes in absorption/emission peak were minimal. To implement such conception, they conjugated chlorambucil and somatostatin receptor (SSTR)–speciﬁc octreotide amide sequentially to a cyanine scaffold, though at different sites [ 34 ]. The conjugated cyanine fluorophore was in NIR emitting enol-form (λ em = 795 nm); after ester biodegradation, it was converted to red emitting ketone-form (λ em = 643 nm).…”

Section: Chemotherapymentioning

confidence: 99%

Cyanine conjugates in cancer theranostics

Yang

Zhou

Yue

et al. 2021

Bioactive Materials

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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.

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“…A more sophisticated theranostic system additionally equipped with a cancer‐specific carrier was lately reported. This TDD system comprised the long‐wavelength, dual fluorescent, switchable cyanine dye IRD bound to CLB by means of a hydrolytically cleavable ester linker (Figure ) . The octreotide amide ( OctA ) peptide, which specifically binds to SSTR‐2 and SSTR‐5 somatostatin receptors overexpressed in many human tumor cells, was used as the carrier.…”

Section: Ratiometric Dd/tdd Monitoringmentioning

confidence: 99%

Fluorescent Reporters for Drug Delivery Monitoring

Patsenker

Gellerman

2019

Israel Journal of Chemistry

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Monitoring of drug delivery is an essential technique for innovative medical treatments, including cancer therapy. Fluorescence imaging has become an important tool in tracking drug delivery and thus improving treatment efficacy. Binding fluorescent reporters to therapeutic agents paves the way to real time monitoring of drug delivery and drug distribution in vitro and in vivo. This review discusses fluorescent reporters used in drug delivery monitoring and provides an overview of recent achievements in the development of fluorescence based drug delivery systems.

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Theranostic system for ratiometric fluorescence monitoring of peptide-guided targeted drug delivery

Abstract: Novel theranostic system that first combines a cancer-targeting peptide with a long-wavelength dual fluorescent dye IRD in order to provide ratiometric monitoring of anticancer drug delivery is developed and evaluated in pancreatic cancer cell line.

Cited by 11 publications

References 45 publications

Drug Combination in Cancer Treatment—From Cocktails to Conjugated Combinations

Drug Combination in Cancer Treatment—From Cocktails to Conjugated Combinations

Cyanine conjugates in cancer theranostics

Fluorescent Reporters for Drug Delivery Monitoring

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