carbocyanines and Skin-Neoplasms

Near-infrared dyes, particularly cyanine dyes, have shown great potential in biomedical imaging due to their deep tissue penetration, high resolution, and minimal tissue autofluorescence/scattering. These dyes can be adjusted in terms of absorption and emission wavelengths by modifying their chemical structures. The current issues with cyanine dyes include aggregation-induced quenching, poor photostability, and short

Topics: Albumins; Carbocyanines; Chlorides; Fluorescent Dyes; Humans; Optical Imaging; Skin Neoplasms

The developing zebrafish is an emerging tool in nanomedicine, allowing non-invasive live imaging of the whole animal at higher resolution than is possible in the more commonly used mouse models. In addition, several transgenic fish lines are available endowed with selected cell types expressing fluorescent proteins; this allows nanoparticles to be visualized together with host cells.. Here, we introduce the zebrafish neural tube as a robust injection site for cancer cells, excellently suited for high resolution imaging. We use light and electron microscopy to evaluate cancer growth and to follow the fate of intravenously injected nanoparticles.. Fluorescently labelled mouse melanoma B16 cells, when injected into this structure proliferated rapidly and stimulated angiogenesis of new vessels. In addition, macrophages, but not neutrophils, selectively accumulated in the tumour region. When injected intravenously, nanoparticles made of Cy5-labelled poly(ethylene glycol)-block-poly(2-(diisopropyl amino) ethyl methacrylate) (PEG-PDPA) selectively accumulated in the neural tube cancer region and were seen in individual cancer cells and tumour associated macrophages. Moreover, when doxorubicin was released from PEG-PDPA, in a pH dependant manner, these nanoparticles could strongly reduce toxicity and improve the treatment outcome compared to the free drug in zebrafish xenotransplanted with mouse melanoma B16 or human derived melanoma cells.. The zebrafish has the potential of becoming an important intermediate step, before the mouse model, for testing nanomedicines against patient-derived cancer cells.. We received funding from the Norwegian research council and the Norwegian cancer society.

Topics: Administration, Intravenous; Animals; Carbocyanines; Cell Line, Tumor; Doxorubicin; Humans; Macrophages; Melanoma, Experimental; Mice; Microscopy, Electron; Nanoparticles; Neoplasm Transplantation; Neural Tube; Neutrophils; Polyethylene Glycols; Polymethacrylic Acids; Skin Neoplasms; Treatment Outcome; Zebrafish

A new type of photodynamic therapy (PDT) agents using upconversion nanoparticles (UCNPs) with incorporated photosensitizers as the inner core and an erythrocyte membrane (RM) decorated with dual targeting moieties as the cloak is developed. Owing to the endogenous nature of RM, the RM-coating endows the PDT agents with perfect biocompatibility and stealth ability to escape from the entrapment by the reticulo-endothelial system (RES). More importantly, owing to the unique nature of erythrocyte as an oxygen carrier in the blood, the RM outer layer of the agents unequivocally facilitates the permeation of ground-state molecular oxygen ((3)O2) and the singlet oxygen ((1)O2) as compared to the previously developed PDT agents with other types of coating. Another salient feature of the as-prepared PDT platform is the decoration of RM with dual targeting moieties for selective recognition of cancer cells and mitochondrial targeting, respectively. The synergistic effect of RM coating and dual-targeting of such feature-packed agents are investigated in tumor-bearing mice and the improved PDT therapeutic efficacy is confirmed, which is the first paradigm where RM-coated NIR-triggered nanovectors with programmed delivery ability is applied in PDT of tumor in vivo.

Topics: Animals; Biomimetic Materials; Carbocyanines; Cell Line, Tumor; Disease Models, Animal; Erythrocyte Membrane; Infrared Rays; Melanoma; Mice; Microscopy, Confocal; Nanoparticles; Photochemotherapy; Photosensitizing Agents; Singlet Oxygen; Skin Neoplasms; Spectroscopy, Near-Infrared; Survival Rate

Hyaluronan (HA), a naturally occurring high Mw (HMw) glycosaminoglycan, has been shown to play crucial roles in cell growth, embryonic development, healing processes, inflammation, and tumor development and progression. Low Mw (LMw, <10 kDa) HA has been reported to provoke inflammatory responses, such as induction of cytokines, chemokines, reactive nitrogen species and growth factors. Herein, we prepared and characterized two types of HA coated (LMw and HMw) lipid-based targeted and stabilized nanoparticles (tsNPs) and tested their binding to tumor cells expressing the HA receptor (CD44), systemic immunotoxicity, and biodistribution in tumor bearing mice. In vitro, the Mw of the surface anchored HA had a significant influence on the affinity towards CD44 on B16F10 murine melanoma cells. LMw HA-tsNPs exhibited weak binding, while binding of tsNPs coated with HMw HA was characterized by high binding. Both types of tsNPs had no measured effect on cytokine induction in vivo following intravenous administration to healthy C57BL/6 mice suggesting no immune activation. HMw HA-tsNPs showed enhanced circulation time and tumor targeting specificity, mainly by accumulating in the tumor and its vicinity compared with LMw HA-tsNPs. Finally, we show that methotrexate (MTX), a drug commonly used in cancer chemotherapy, entrapped in HMw HA-tsNPs slowly diffused from the particles with a half-life of 13.75 days, and improved the therapeutic outcome in a murine B16F10 melanoma model compared with NPs suggesting an active cellular targeting beyond the Enhanced Permeability and Retention (EPR) effect. Taken together, these findings have major implications for the use of high molecular weight HA in nanomedicine as a selective and safe active cellular targeting moiety.

Topics: Animals; Antimetabolites, Antineoplastic; Carbocyanines; Cell Line, Tumor; Cytokines; Drug Carriers; Female; Half-Life; Hyaluronan Receptors; Hyaluronic Acid; Lipids; Methotrexate; Mice; Mice, Inbred C57BL; Molecular Weight; Nanomedicine; Nanoparticles; Protein Binding; Skin Neoplasms; Tissue Distribution

Angioleiomyoma is frequently painful and the cause of the pain is unknown. The purpose of this study was to compare the mast cell population and innervation of painful and painless angioleiomyomas. Twenty-four cases of angioleiomyoma were examined; 16 painful and 8 painless cases. Pinacyanol erythrosinate and antibodies to protein gene product (PGP) 9.5 were used to demonstrate mast cells and nerves respectively. PGP 9.5-immunoreactive nerve fibres were found in most of the painful (13/16 cases) and painless lesions (5/8). Mast cells were not seen in half of the painful lesions but were seen in most of the painless lesions (7/8). The median mast cell density was 1.1 cells/mm2 for the painful lesions and 21.9 cells/mm2 for the painless lesions (P = 0.048, Mann-Whitney test). The lower mast cell density in the painful lesions may reflect increased mast cell degranulation. It is proposed that neural and vascular events, similar to those occurring in the triple response to mild cutaneous injury, may produce pain in angioleiomyoma and other painful skin tumours.

Topics: Carbocyanines; Erythrosine; Hemangioma; Humans; Immunoenzyme Techniques; Leiomyoma; Mast Cells; Nerve Fibers; Pain; Skin Neoplasms; Thiolester Hydrolases; Ubiquitin Thiolesterase