cypate and Neoplasms

Topics: Cell Line, Tumor; Humans; Nanoparticles; Neoplasms; Peptides; Precision Medicine; Tumor Microenvironment

Defect-engineered porphyrinic MOF nanoparticles were fabricated with an in situ one-pot protocol using cypate as the co-ligand and modulator. This multifunctional nanoplatform integrated the photothermal and multimodal imaging properties of cypate with the photodynamic effects of porphyrins, thus achieving targeted multimodal cancer phototheranostics after folic acid modification.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Folic Acid; Humans; Indoles; Metal-Organic Frameworks; Mice; Nanoparticles; Neoplasms; Neoplasms, Experimental; Optical Imaging; Photochemotherapy; Photosensitizing Agents; Porphyrins; Propionates; Reactive Oxygen Species; Theranostic Nanomedicine

Synergistic thermo-chemotherapy based multiple stimuli-responsive drug delivery systems have achieved significant improvement of cancer curative effects compared with single modality treatment. Nevertheless, the efficacy of thermo-chemotherapy is often reduced in drug-resistant tumors and the therapy method is unexpectedly associated with potential toxicity by utilizing poorly degradable materials. Here, we report a simple approach to encapsulate three drug payloads into multi-sensitive and degradable nanospheres (SDC@NS) to achieve anticancer effects. SDC@NS comprise a photothermal agent (cypate), an anticancer agent (doxorubicin), and a nitric oxide donor (SNAP) to achieve controllable drugs release in high concentration glutathione or under near-infrared light (NIR) irradiation. Hyperthermia from NIR-mediated cypate can accelerate cancer cell apoptosis in vitro and tumor tissue ablation in vivo. Furthermore, our results also confirmed that the nitric oxide-based SDC@NS showed significant cytotoxicity compared to the nitric oxide absent group (denoted as DC@NS) and an enhanced chemotherapy effect in vivo. The photothermal effect and payloads can synchronously realize cancer therapy and provide a new insight into the enhanced synergistic therapeutic effect.

Topics: Animals; Apoptosis; Combined Modality Therapy; Doxorubicin; Drug Delivery Systems; Drug Liberation; Humans; Hyperthermia, Induced; Indoles; Infrared Rays; LLC-PK1 Cells; MCF-7 Cells; Mice, Inbred C57BL; Nanospheres; Neoplasms; Nitric Oxide; Propionates; Swine; Xenograft Model Antitumor Assays

From the conception of atom economy to develop multifunctional nanomaterials, it is important to construct nanomaterials by maximizing functional units while minimizing unnecessary components. Noteworthy, metal-organic framework (MOF) nanoparticles are excellent examples to meet this idea. Current approaches for multifunctional MOFs are mainly based on encapsulation of functional molecules or multistep modification; however, high risk for leakage and burst release and time-consuming and complicated organic synthesis limit their applications. Here, we report a one-pot approach to build the defect structure of a metal organic framework with near-infrared dye (cypate), which is based on the interaction between Fe

Topics: Animals; Cell Line, Tumor; Cell Survival; Fluorescent Dyes; Humans; Indoles; Infrared Rays; Male; Metal-Organic Frameworks; Mice; Mice, Inbred BALB C; Mice, Nude; Multimodal Imaging; Nanoparticles; Neoplasms; Phototherapy; Propionates; Reactive Oxygen Species; Spectroscopy, Near-Infrared; Tissue Distribution; Transplantation, Heterologous

Near-infrared (NIR) imaging is a promising technique for use as a noninvasive and sensitive diagnostic tool. Although the NIR fluorescently labeled glucose analog glucosamine (cypate-glucosamine) has applications in preclinical imaging, the transport pathways and fate of this probe in tissues remain unaddressed. Here, we have synthesized and characterized cypate and cypate-glucosamine conjugate (cy-2-glu), and investigated the probable transport pathways of these probes in vitro and in vivo. We compared uptake of the probes in the presence and absence of excess d-glucose, "saturated cypate" and palmitic acid in two normal-cancer cell line pairs: lung cancer (A549)-normal (MRC9) and prostate cancer (DU145)-normal (BPH). Breast cancer (MDA-MB-231) and liver cancer (HepG2) cell lines were also examined. Results support use of the glucose transport pathway by cy-2-glu and fatty acid transport pathway by cypate. Mass spectrometry data on the in vitro extracts revealed deamidation of cy-2-glu in prostate and liver cells, suggesting release of glucosamine. In vivo biodistribution studies in mice engrafted with breast tumors showed a distinct accumulation of cy-2-glu in liver and tumors, and to a lesser extent in kidneys and spleen. A negligible accumulation of cypate alone in tumors was observed. Analysis of urine extracts revealed renal excretion of the cy-2-glu probe in the form of free cypate, indicating deamidation of cy-2-glu in tissues. Thus, investigation of the metabolic pathways used by NIR probes such as cy-2-glu advances their use in the detection and monitoring of tumor progression in preclinical animal studies.

Topics: A549 Cells; Animals; Cell Line, Tumor; Disease Progression; Fluorescent Dyes; Glucosamine; Glucose; Hep G2 Cells; Humans; Indoles; Metabolic Networks and Pathways; Mice; Mice, Nude; Neoplasms; Pilot Projects; Propionates; Spectroscopy, Near-Infrared; Tissue Distribution

Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), is a promising noninvasive strategy in the treatment of cancers due to its highly localized specificity to tumors and minimal side effects to normal tissues. However, single phototherapy often causes tumor recurrence which hinders its clinical applications. Therefore, developing a NIR-guided dendritic nanoplatform for improving the phototherapy effect and reducing the recurrence of tumors by synergistic chemotherapy and phototherapy is essential.. A fluorescent targeting ligand, insisting of ICG derivative cypate and a tumor penetration peptide iRGD (CRGDKGPDC), was covalently combined with PAMAM dendrimer to prepare a single agent-based dendritic theranostic nanoplatform iRGD-cypate-PAMAM-DTX (RCPD).. Compared with free cypate, the resulted RCPD could generate enhanced singlet oxygen species while maintaining its fluorescence intensity and heat generation ability when subjected to NIR irradiation. Furthermore, our in vitro and in vivo therapeutic studies demonstrated that compared with phototherapy or chemotherapy alone, the combinatorial chemo-photo treatment of RCPD with the local exposure of NIR light can significantly improve anti-tumor efficiency and reduce the risk of recurrence of tumors.. The multifunctional theranostic platform (RCPD) could be used as a promising method for NIR fluorescence image-guided combinatorial treatment of tumor cancers.

Topics: Animals; Antineoplastic Agents; Cell Proliferation; Combined Modality Therapy; Dendrimers; Docetaxel; Endocytosis; Fluorescence; Hep G2 Cells; Hot Temperature; Humans; Indoles; Infrared Rays; Mice, Nude; Nanoparticles; Neoplasms; Oligopeptides; Photochemotherapy; Phototherapy; Propionates; Reactive Oxygen Species; Theranostic Nanomedicine

Tumor hypoxia strikingly restricts photodynamic therapy (PDT) efficacy and limits its clinical applications in cancer therapy. The ideal strategy to address this issue is to develop oxygen-independent PDT systems. Herein, the rationally designed tumor pH-responsive polymeric micelles are devised to realize oxygen-independent combined PDT and photothermal therapy (PTT) under near-infrared light (NIR) irradiation. The triblock copolymer, poly(ethylene glycol)-b-poly(ε-caprolactone)-b-poly(2-(piperidin-1-yl)ethyl methacrylate) (PEG-b-PCL-b- PPEMA), was prepared to co-encapsulate cypate and singlet oxygen donor (diphenylanthracene endoperoxide, DPAE) via self-assembly to obtain the micellar delivery system (C/O@N-Micelle). C/O@N-Micelle showed remarkable tumor accumulation and improved cellular internalization (2.1 times) as the pH value was changed from 7.4 during blood circulation to 6.8 in tumor tissues. The micelles could produce a potent hyperthermia for PTT of cypate under 808 nm NIR irradiation, which simultaneously induced thermal cycloreversion of DPAE generating abundant singlet oxygen for PDT without participation of tumor oxygen. Finally, the photothermally triggered PDT and PTT combination achieved efficient tumor ablation without remarkable systemic toxicity in an oxygen-independent manner. This work represents an efficient strategy for oxygen-independent combined PDT and PTT of cancers under NIR irradiation through co-encapsulation of cypate and DPAE into tumor pH-responsive polymeric micelles.

Topics: Animals; Anthracenes; Cell Line, Tumor; Combined Modality Therapy; Delayed-Action Preparations; Drug Delivery Systems; Female; Hydrogen-Ion Concentration; Hyperthermia, Induced; Indoles; Lactones; Mice, Inbred BALB C; Micelles; Neoplasms; Photochemotherapy; Photosensitizing Agents; Phototherapy; Polyethylene Glycols; Polymethacrylic Acids; Propionates; Singlet Oxygen; Tumor Hypoxia

Chemotherapeutic drugs frequently encounter multiple drug resistance in the field of cancer therapy. The strategy has been explored with limited success for the ablation of drug-resistant tumor via intravenous administration. In this work, the rationally designed light-triggered nanoparticles with multipronged physicochemical and biological features are developed to overcome cisplatin resistance via the assembly of Pt(IV) prodrug and cyanine dye (Cypate) within the copolymer for efficient ablation of cisplatin-resistant tumor. The micelles exhibit good photostability, sustained release, preferable tumor accumulation, and enhanced cellular uptake with reduced efflux on both A549 cells and resistant A549R cells. Moreover, near-infrared light not only triggers the photothermal effect of the micelles for remarkable photothermal cytotoxicity, but also leads to the intracellular translocation of the micelles and reduction-activable Pt(IV) prodrug into cytoplasm through the lysosomal disruption, as well as the remarkable inhibition on the expression of a drug-efflux transporter, multidrug resistance-associated protein 1 (MRP1) for further reversal of drug resistance of A549R cells. Consequently, the multipronged effects of light-triggered micelles cause synergistic cytotoxicity against both A549 cells and A549R cells, and thus efficient ablation of cisplatin-resistant tumor without regrowth. The multipronged features of light-triggered micelles represent a versatile synergistic approach for the ablation of resistant tumor in the field of cancer therapy.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cisplatin; Delayed-Action Preparations; Drug Resistance, Neoplasm; Female; Fluorescent Dyes; Humans; Indoles; Light; Mice; Mice, Inbred BALB C; Mice, Nude; Micelles; Nanoparticles; Neoplasms; Platinum; Prodrugs; Propionates

A new near-infrared fluorescent compound containing two cyclic RGD motifs, cypate-[c(RGDfK)](2) (1), was synthesized based on a carbocyanine fluorophore bearing two carboxylic acid groups (cypate) for integrin α(v)β(3)-targeting. Compared with its monovalent counterpart cypate-c(RGDfK) (2), 1 exhibited remarkable improvements in integrin α(v)β(3) binding affinity and tumor uptake in nude mice of A549. The results suggest that cypate-linked divalent ligands can serve as an important molecular platform for exploring receptor-targeted optical imaging and treatment of various diseases.

Topics: Animals; Carbocyanines; Cell Line, Tumor; Fluorescent Dyes; Humans; Integrin alphaVbeta3; Mice; Mice, Nude; Neoplasms; Oligopeptides; Optical Imaging