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Cypate
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2020 · IF 3.99

TPGS and cypate gated mesoporous carbon for enhanced thermochemotherapy of tumor

Qinfu Zhao,Xian Li,Junya Lu,Yixuan Liu,Luping Sha,Donghua Di,Siling Wang

Thermo-chemotherapy could improve the therapeutic effects of single chemotherapy with the help of cytotoxic heat produced by the PTT (photothermal therapy). The photothermal conversion property of material needs to be preferentially considered in the design the drug delivery in the thermo-chemotherapy. Therefore, in this work, mesoporous carbon nanoparticles (MCN) with excellent heat generating efficiency and high surface area was designed. And the NIR absorbing dye cypate was conjugated on the surface of MCN by the cleavable disulfide bonds to hinder the premature release of doxorubicin (DOX) and enhance the photothermal properties of MCN-based delivery systems. And then TPGS was further covered on the surface of MCN by hydrophobic force to prolong circulation time and improve the biocompatibility and dispersion stability of MCN-CyT in physiological environment. The release of DOX accelerated obviously in the presence of glutathione (GSH), acidic condition and NIR irradiation, indicating that DOX/MCN-CyT exhibited redox/pH/NIR triple-triggered drug release. The anti-tumor experiment indicated that DOX/MCN-CyT showed a synergistic thermo-chemotherapy effect for cancer. Thus, the present research provides huge potential in multi-triggered drug delivery and thermochemotherapy for combination therapy.

研究领域: 生物医学工程 · 纳米医学 · 肿瘤学
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES · 2023 · IF 3

Development of a sensitive LC-MS/MS method for the quantification of theranostic agent cypate in mouse plasma and application to a pharmacokinetic study

Zheyue Bo,Wanjun Han,Haoyue Zhao,Han Liu,Ting Liang,Lanjing Li,Taotao Peng,Ying Li,Chunshan Gui

Cypate, a heptamethine cyanine dye, is a prototypic near-infrared (NIR) theranostic agent for optical imaging and photothermal therapy. In the present study, a selective, sensitive, and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitation of cypate in mouse plasma. The chromatographic separation was achieved using a short C 18 column (2.1 mm × 50 mm, 5 μm) with a run time of 5 min. The MS was operated in multiple reaction monitoring (MRM) mode via positive electrospray ionization. The ion transitions for cypate and internal standard IR-820 were m / z 626.3 → 596.3 and m / z 827.4 → 330.2, respectively. The method was linear over a concentration range of 1.0–500 ng/mL. The within-run and between-run precision was less than 14.4% with accuracy in the range of −13.4% ∼ 9.8%. The validated method was successfully applied to a pharmacokinetic study of cypate in mice following intravenous administration.

CAS / MDL: 631-61-8 64-18-6
研究领域: 分析化学 · 药理学 · 医学
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Journal of Biophotonics · 2017 ·Vol. 10 ·期 12 ·1607-1616 · IF 4.328

Cypate-mediated thermosensitive nanoliposome for tumor imaging and photothermal triggered drug release

Zhihao Han,Liwei Lv,Yi Ma,Zhaohui Wang,Yuxi Liu,Min Zhang,Siwen Li,Yueqing Gu

It is an emerging focus to explore controlled release drug delivery systems for simultaneous cancer imaging and therapy. Herein, we synthesized a photothermal sensitive multifunctional nano-liposome drug delivery system, with doxorubicin wrapped in the hydropholic layer as the therapeutical agent and cypate doped in the hydrophobic layer as the diagnostic agent. A series of in vitro and in vivo characterization demonstrated the stability of synthesized liposome, as the DL% was 9 ± 1.5 and the EE% was 82.7 ± 2.1. And the liposome achieved the functions of target-delivery, enhanced photochemical internalized drug release, and simultaneous chemotherapy and thermal therapy, indicating that this multifunctional nano-liposome is a promising drug delivery system for tumor diagnosis and targeting therapy.

CAS / MDL: 5471-63-6 9002-93-1
研究领域: 药剂学 · 肿瘤学 · 生物医学工程
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Cypate-sensitized upconversion nanoprobes for intracellular and in-vivo ATP ratiometric detection

Wusen Zhou,Jiacheng Gong,Shan Lu,Zhuo Li,Yan Long,Xingjun Li,Renfu Li,Xiaoying Shang,Yan Liu,Datao Tu,Zhuo Chen,Xueyuan Chen

As energy currency of life, adenosine triphosphate (ATP) is highly dynamic in living organisms. It is crucial yet challenging to probe intracellular or in-vivo ATP precisely without destruction of the living biological systems. Herein, we have designed novel ATP-responsive ratiometric nanoprobes by employing upconversion nanoparticles (UCNPs) with cypate as antennas. Nuclear magnetic resonance spectroscopy was used to analyze the interfacial interactions among lanthanide nanocrystal, cypate and adenosine phosphates, disclosing the origin of detection specificity. ATP induced interruption of energy transfer pathway in cypate-sensitized UCNPs was further investigated by femtosecond transient absorption and time-resolved photoluminescence spectroscopy. The nanoprobes with dual near-infrared (NIR)-excited ratiometric UCL were successfully applied for quantification of ATP level in living cells under vegetatively growing, starving, and glycolysis-inhibiting states, respectively. Furthermore, the increase of available energy by feeding for zebrafish larvae was confirmed through monitoring the in-vivo ATP variation with the nanoprobes. Such nanoprobes showed great potential in ATP-associated biological research and clinical applications. These findings may gain deep insights into the surface science and photophysics in dye-lanthanide nanocomposites, and open new avenues for the design and bioapplications of lanthanide nanoprobes.

研究领域: 生物化学 · 纳米医学 · 分析化学
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2020 · IF 3.99

Redox/NIR dual-responsive PEG-betulinic acid/pluronic-cypate prodrug micelles for chemophotothermal therapy

Yunran Zhang,Haiping Zhou,Zhe Zhang,Yijun Zhu,Tao Wang,Liguo Yu,Hongrui Song

Betulinic acid (BA) is a new class of anticancer drug , but its relatively short half-life and poor water solubility limit its therapeutic effect and clinical application. Herein, to tackle the dilemma, BA prodrugs were prepared by conjugating BA onto the polyethylene glycol (PEG) polymer via cleavable disulfide bonds. The prodrugs exhibited high water solubility (270-fold of free BA) and a relatively high drug-loading efficiency of 14.2 %. To further endow the BA prodrugs with a photothermal therapeutic effect, the near-infrared (NIR) agent Cypate was grafted on the Pluronic triblock copolymer . The different PEG polymers and different Pluronic polymers were chosen to obtain the optimal drug loading efficiency and the photothermal generation effect. The P-SS-BA/F68-Cy prodrug micelles integrate the redox-responsive BA prodrugs and the NIR-responsive amphiphilic triblock polymer into one single nanocomposite . The release of BA was less than 20 % in pH 7.4 PBS in the absence of glutathione (GSH), whereas the release of BA was obviously accelerated in pH 5.0 PBS with 10 mM GSH. In addition, the release of BA was further accelerated under the NIR irradiation. The P-SS-BA/F68-Cy micelles showed an excellent photothermal heating effect under NIR irradiation. The prepared P-SS-BA/F68-Cy micelles showed the synergistic thermochemotherapeutic effect on tumors both in vitro and in vivo . Therefore, the present study shows the great potential of dual-triggered drug delivery and thermochemotherapy for combination therapy.

研究领域: 药学 · 肿瘤学 · 生物材料学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2026 · IF 5.6

Organic Nano-Quantum Dots of Salvianolic Acid B Modified with Photosensitive Cypate for Diagnosis and Treatment of Myocardial

Na Wang,Ye Zhang,Wen Huang,Wei Du,Chunhua Ma,YuQiang Fang,Chunyu Zeng

Salvianolic acid B (SaB) demonstrates significant cardioprotective effects against myocardial ischemia–reperfusion injury (I/R). However, its clinical application is limited by rapid metabolism and poor bioavailability. To address this, we synthesized SaB-loaded organic quantum dots (SaB@qd) via a hydrothermal method and functionalized them with the near-infrared (NIR) dye cypate (SaB@qd@Cy). Proteomic analysis of cardiac tissues from I/R model rats identified SIRT2 as a key downregulated protein. Molecular docking and cell membrane chromatography confirmed SaB as a natural SIRT2 agonist, binding specifically to the SER-263 residue. SaB@qd@Cy enhanced myocardial SaB accumulation by 3.2-fold compared to free SaB (P<0.01). In vivo, SaB@qd@Cy reduced the infarct area by 41% (compared to 28% reduction by mitochondrial-targeted CoQ10 nanoparticles) and attenuated inflammatory cytokine expression (IL-1β, TNF-α) via the SIRT2/NLRP3 pathway. Additionally, cypate enabled real-time NIR imaging of ischemic borders, with a temperature increase of 15.3±1.2°C under 808   nm laser irradiation. This study presents a novel theranostic nanoplatform that integrates natural compounds with photoresponsive quantum dots for targeted therapy and intraoperative imaging in I/R management.

CAS / MDL: 25322-68-3 95837-47-1
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Polymer Chemistry · 2014 ·Vol. 5 ·期 11 ·3707-3718 · IF 5.368

Redox-responsive core cross-linked micelles based on cypate and cisplatin prodrugs-conjugated block copolymers for synergistic photothermal–chemotherapy of cancer

Yu Han,Junjie Li,Minghui Zan,Shizhong Luo,Zhishen Ge,Shiyong Liu

Responsive cross-linked block copolymer micelles which have emerged as promising drug delivery systems showed high stability and on-demand drug release. The combination therapy of cancer can be achieved via co-delivery of varying therapeutic molecules in one system. Here, we developed a redox-responsive core cross-linked (CCL) micelle conjugated with cypate and cisplatin prodrugs within the cores for synergistic photothermal and chemotherapy. The block copolymer, poly[(2-(2-methoxyethoxy)ethyl methacrylate)-co-(N-methacryloxy succinimide)]-block-poly(N-(2-hydroxypropyl) methacrylamide) (P(MEO2MA-co-MASI)-b-PHPMA), was synthesized via reversible addition–fragment chain transfer (RAFT) polymerization. After partial amidation reaction of succinimide with 3-azidopropylamine, the alkynyl-functionalized cypate and Pt(IV) complex were conjugated via click reaction. The CCL micelles were fabricated by core cross-linking at 37 °C in aqueous solution using cystamine as the cross-linker. P(Pt-Cy-MEO2MA)-b-PHPMA CCL micelles showed redox-responsive cross-linker cleavage and cisplatin drug release in the presence of reductants. The conjugated cypate moieties in the cores of CCL micelles resulted in photothermal temperature increase and reactive oxygen species (ROS) generation under 805 nm near infrared (NIR) laser irradiation. The cytotoxicity of CCL micelles was investigated with and without NIR irradiation. A significant synergistic effect of photothermal therapy and chemotherapy was demonstrated against cisplatin-resistant human lung cancer cells A549R under NIR irradiation.

研究领域: 癌症治疗 · 药物递送系统 · 高分子化学 · 纳米医学
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MOLECULAR PHARMACEUTICS · 2024 · IF 4.5

Self-Delivery Nanomedicines Reverse Thermal Resistance to Enhance Tumor Mild-Temperature Photothermal Therapy

Jinmei Lai,Qunying Shi,Yongqi Xie,Yinyin Zhu,Shiyu Liang,Yi Chen,Jiali Yuan,Lihan Liu

Tumoral thermal defense mechanisms considerably attenuate the therapeutic outcomes of mild-temperature photothermal therapy (PTT). Thus, developing a simple, efficient, and universal therapeutic strategy to sensitize mild-temperature PTT is desirable. Herein, we report self-delivery nanomedicines ACy NPs comprising a near-infrared (NIR) photothermal agent (Cypate), mitochondrial oxidative phosphorylation inhibitor (ATO), and distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE–PEG2000), which have a high drug-loading efficiency that can reverse tumoral thermal resistance, thereby increasing mild-temperature PTT efficacy. ACy NPs achieved targeted tumor accumulation and performed NIR fluorescence imaging capability in vivo to guide tumor PTT for optimized therapeutic outcomes. The released ATO reduced intracellular ATP levels to downregulate multiple heat shock proteins (including HSP70 and HSP90) before PTT, which reversed the thermal resistance of tumor cells, contributing to the excellent results of mild-temperature PTT in vitro and in vivo. Therefore, this study provides a simple, biosafe, advanced, and universal heat shock protein-blocking strategy for tumor PTT.

CAS / MDL: 41532-84-7
研究领域: 纳米技术 · 肿瘤学 · 治疗诊断学 · 生物医学工程
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