Preliminary Structure–activity Relationship Study of Heptamethine Indocyanine Dyes for Tumor-Targeted Imaging

Guo, Qinyuan; Luo, Shenglin; Qi, Qingrong; Chen, Shi

doi:10.1142/s179354581350003x

Cited by 14 publications

(13 citation statements)

References 18 publications

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“…They exhibit to retain preferentially in a broad‐spectrum of cancer cells and accumulate at cellular mitochondria. Our structure‐activity relationship study and other reports also indicate that the heptamethine core with lipophilic cationic property is essential for mitochondrial targeting and imaging. In addition, certain cyanine dyes have been demonstrated with photosensitization effects, which are closely associated with their lipo‐hydro partition coefficients (log P ), polarizabilities, and molar absorption coefficients .…”

Section: Introductionsupporting

confidence: 78%

Mitochondria‐Targeted Small‐Molecule Fluorophores for Dual Modal Cancer Phototherapy

Luo

Tan

Fang

et al. 2016

Adv Funct Materials

Self Cite

261

202

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Mitochondria are recognized as the ideal target for cancer treatment because they play a central role in oxidative metabolism and apoptosis. In this work, a mitochondria‐targeted near‐infrared (NIR) photosensitizer (PS) for synchronous cancer photodynamic therapy (PDT) and photothermal therapy (PTT) is synthesized. This multifunctional small‐molecule PS is developed from a variety of synthesized heptamethine cyanine dyes, which are modified with various N‐alkyl side chains on the lipophilic cationic heptamethine core. It is demonstrated to preferentially accumulate in cancer cells by organic‐anion transporting polypeptide mediated active transport and retain in mitochondria by its lipophilic cationic property. As mitochondria are susceptible to hyperthermia and excessive reactive oxygen species, this new PS integrating PTT and PDT treatment exhibits highly efficient phototherapy in multiple cancer cells and animal xenograft models. Furthermore, this targeted PS with NIR imaging property also enables tumors and their margins clearly visualized, providing the potential for precisely imaging‐guided phototherapy and treatment monitoring. This is the first report that a small‐molecule PS integrates both cancer PTT and PDT treatment by targeting mitochondria, significantly increasing the photosensitization. This work may also present a practicable strategy to develop small‐molecule‐based cancer theranostic agents for simultaneous cancer targeting, imaging, and therapy.

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Section: Introductionsupporting

confidence: 78%

Mitochondria‐Targeted Small‐Molecule Fluorophores for Dual Modal Cancer Phototherapy

Luo

Tan

Fang

et al. 2016

Adv Funct Materials

Self Cite

261

202

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“…In our recent work, we have identified a class of lipophilic NIR fluorescent heptamethine cyanine dyes, which are able to preferentially accumulate into cell mitochondria and possess unique optical properties for in vivo cell tracking and biomedical imaging . Our structure–activity relationship study and other reports have indicated that the heptamethine core with lipophilic cationic property is essential for mitochondrial targeting. Based on these foregoing studies, in this work, we designed and synthesized a series of heptamethine dyes modified with various N ‐alkyl side chains around the heptamethine core, and successfully developed a new derivative, termed NIR cell protector‐61 (NIRCP‐61), which maintains the superior optical imaging properties and significantly decreases the cell contamination.…”

Section: Introductionmentioning

confidence: 65%

Development of Therapeutic Small‐Molecule Fluorophore for Cell Transplantation

Wang

Chen

Luo

et al. 2016

Adv Funct Materials

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Cell transplantation holds great promise in regenerative medicine but restricted cell survival and tracking severely limited their therapeutic efficacy. The development of multifunctional agents to simultaneously address these challenges will be very helpful in cytotherapy. Near‐infrared (NIR) imaging is being increasingly used for in vivo cell tracking, but the extensive cell contamination and potential cytotoxicity of current membrane lipophilic dyes severely limit their potentialuse in clinical applications. Here, a novel mitochondrial heptamethine dye, NIR cell protector‐61 (NIRCP‐61), is designed and synthesized via modification of N‐alkyl side chains around a heptamethine core, which maintains the superior fluorescent imaging properties and significantly decreases cell contamination. Further, NIRCP‐61 also significantly alleviates cell damage from acute oxidative stress and improves their therapeutic outcome in multiple animal models. This cytoprotective effect is mediated by evoking the intracellular antioxidant defense mechanisms of nuclear factor erythroid 2‐related factor 2 (Nrf2) and phosphoinositide 3‐kinase/protein kinase B (PI3K/Akt) pathways. NIRCP‐61 is the first NIR agent that simultaneously meets the requirements for both cell tracking and cytoprotection. Therefore, NIRCP‐61 may represent an attractive therapeutic fluorophore for cell transplantation and offers a convenient way to impel potential translation in clinical cell‐based therapies.

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“…They have been extensively explored to probe aspects of mitochondrial physiology, including mitophagy, membrane potential, pH, polarity, glutathione, cysteine, ROS, and nitroreductase activity [ 4 , 63 ]. Apparently, the heptamethine core of cyanine dyes plays a key role in mitochondrial targeting [ 63 , 64 , 65 ]. Some cyanine dyes can serve as PSs, which may be related to their molar absorption coefficients, polarizability, and lipo-hydropartition coefficients [ 66 , 67 ].…”

Section: Strategies For Mitochondria-targeted Ptmentioning

confidence: 99%

Improving the Phototherapeutic Efficiencies of Molecular and Nanoscale Materials by Targeting Mitochondria

Lin

Bao

2018

Molecules

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Mitochondria-targeted cancer phototherapy (PT), which works by delivering photoresponsive agents specifically to mitochondria, is a powerful strategy to improve the phototherapeutic efficiency of anticancer treatments. Mitochondria play an essential role in cellular apoptosis, and are relevant to the chemoresistance of cancer cells. Furthermore, mitochondria are a major player in many cellular processes and are highly sensitive to hyperthermia and reactive oxygen species. Therefore, mitochondria serve as excellent locations for organelle-targeted phototherapy. In this review, we focus on the recent advances of mitochondria-targeting materials for mitochondria-specific PT. The combination of mitochondria-targeted PT with other anticancer strategies is also summarized. In addition, we discuss both the challenges currently faced by mitochondria-based cancer PT and the promises it holds.

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Preliminary Structure–activity Relationship Study of Heptamethine Indocyanine Dyes for Tumor-Targeted Imaging

Cited by 14 publications

References 18 publications

Mitochondria‐Targeted Small‐Molecule Fluorophores for Dual Modal Cancer Phototherapy

Mitochondria‐Targeted Small‐Molecule Fluorophores for Dual Modal Cancer Phototherapy

Development of Therapeutic Small‐Molecule Fluorophore for Cell Transplantation

Improving the Phototherapeutic Efficiencies of Molecular and Nanoscale Materials by Targeting Mitochondria

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