RESUMEN
Thanks to deep penetration and high resolution, the second near-infrared window (NIR-II, 1000-1700 nm) fluorescence (FL) imaging is expected to gain favor in clinical applications, including macroscopic imaging for cancer diagnosis and microangiography for vascular-related disease diagnosis. Nevertheless, most NIR-II fluorescent probes, especially cyanine, are highly susceptible to self-quenching in the aggregated state, which severely limits their application in bioimaging. Here, the Br-modified cyanine dye F4 -Br and the amphiphilic polypeptide poly(oligo[ethylene glycol]methacrylate)-b-poly(benzyl-L-aspartic acid) (POEGMA-PBLA) are synthesized. By modulating the self-assembly of F4 -Br and POEGMA-PBLA to effectively inhibit the H-aggregation of F4 -Br in aqueous solutions, nanoprobe F4 -Br@P17 with outstanding antiquenching capability is developed. This prominent feature allows it to perform vascular microscopic imaging with high spatiotemporal resolution and assess hemodynamic characteristics. F4 -Br@P17 nanoparticles (NPs) with good stability and satisfactory biocompatibility also enable high contrast brightness for NIR-II FL imaging of tumors. Given the efficient enrichment at tumor sites and the promising photothermal conversion efficiency (43.5%), F4 -Br@P17 NPs successfully conduct photothermal therapy and exhibit superior antitumor efficiency under 1064 nm laser irradiation. These remarkable performances reveal the tremendous possibility of F4 -Br@P17 NPs for in vivo microscopic imaging and FL imaging-guided photothermal therapy in the NIR-II region.
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Nanopartículas , Neoplasias , Humanos , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Polietilenglicoles , Imagen Óptica , Péptidos , Línea Celular Tumoral , FototerapiaRESUMEN
With the continuous development of organic materials for optoelectronic devices and biological applications, J-aggregation has attracted a great deal of interest in both dye chemistry and supramolecular chemistry. Except for the characteristic red-shifted absorption and emission, such ordered head-to-tail stacked structures may be accompanied by special properties such as enhanced absorption, narrowed spectral bandwidth, improved photothermal and photodynamic properties, aggregation-induced emission enhancement (AIEE) phenomenon, and so forth. These excellent properties add great potential to J-aggregates for optical imaging and phototherapy in the near-infrared (NIR) region. Despite decades of development, the challenge of rationally designing the molecular structure to adjust intermolecular forces to induce J-aggregation of organic dyes remains significant. In this review, we discuss the formation of J-aggregates in terms of intermolecular interactions and summarize some recent studies on J-aggregation dyes for NIR imaging and phototherapy, to provide a clear direction and reference for designing J-aggregates of near-infrared organic dyes to better enable biological applications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
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Colorantes Fluorescentes , Nanopartículas , Colorantes Fluorescentes/química , Fototerapia , Imagen Óptica/métodos , Nanopartículas/químicaRESUMEN
The second near-infrared IIa window (NIR-IIa, 1300nmâ¼1400nm) enables high-resolution imaging and deep-tissue tumor treatment due to its unique low tissue scattering and autofluorescence, high temporal-spatial resolution, and deep tissue penetration. Therefore, NIR-IIa fluorescence imaging-guided phototherapy is of specific interest. However, organic dyes and their nanoparticles for NIR-IIa phototheranostics are still scarce. Here, we have synthesized a Br- and piperazine-modified cyanine dye (FN) and its nanomicelles encapsulated by an amphiphilic polypeptide with sidechains of tertiary amine (PEA). The J-aggregates of P@FN9 with 1116 nm absorption and efficient NIR-IIa fluorescence emission were formed by the self-assembly of FN and PEA. P@FN9 nanoparticles (NPs) showed good stability and high photothermal conversion efficiency (55.4%). In addition, the high spatial resolution and signal-to-background ratio (SBR) of P@FN9 were demonstrated by NIR-IIa fluorescence imaging of mouse vasculature. The P@FN9 NPs successfully performed the NIR-IIa fluorescence imaging-guided photothermal therapy, and both in vitro and in vivo experiments indicated that the P@FN9 NPs exhibited effective antitumor effects under the NIR-II (1064 nm) laser irradiation. STATEMENT OF SIGNIFICANCE.
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Nanopartículas , Neoplasias , Animales , Ratones , Piperazina , Fototerapia , Imagen Óptica , Nanopartículas/uso terapéutico , Colorantes , Neoplasias/terapia , Péptidos/farmacología , Línea Celular TumoralRESUMEN
For photothermal therapy (PTT), the improved targeting can decrease the dosage and promote the therapeutic function of photothermal agents, which would effectively improve the antitumor effect. The tumor microenvironment (TME) and cells are targets in designing intelligent and responsive theranostics. However, most of these schemes have been limited to the traditional visible and first near-infrared (NIR-I) regions, eager to expand to the second near-infrared (NIR-II) window. We designed and synthesized a polyethylene glycol conjugated and disulfide-modified macromolecule fluorophore (MPSS). MPSS could self-assemble into core-shell micelles in an aqueous solution (MPSS-NPS), while the small molecule probes were in a high aggregation arrangement inside the nanoparticle. The pronounced aggregation quenching (ACQ) effect caused them to the "sleeping" state. After entering the tumor cells, the disulfide bonds in MPSS-NPS broke in response to a high concentration of glutathione (GSH) in TME, and the molecule probes were released. The highly aggregated state was effectively alleviated, resulting in distinct absorption enhancement in the near-infrared region. Therefore, the fluorescence signal was recovered, and the photothermal performance was triggered. In vitro and in vivo studies reveal that the Nano-system is efficient for the smart NIR-II fluorescence imaging-guided PTT, even at a low dosage and density of irradiation.
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Nanopartículas , Neoplasias , Línea Celular Tumoral , Disulfuros , Colorantes Fluorescentes/química , Glutatión , Humanos , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Fototerapia , Nanomedicina Teranóstica/métodos , Microambiente TumoralRESUMEN
A novel NIR-II small-molecule D-A type organic fluorophore conjugation of triphenylamine, thiophene, and benzo[c,d] indol groups (TPA-Et) with strong electron-donating and accepting groups has been synthesized. The dye shows a significant Stokes shift for efficient fluorescence in the NIR-II region and high photothermal performance. The TPA-Et was then encapsulated by an amphiphilic copolymer P(OEGMA)20-P(Asp)14, and micelles (P@TP) has been prepared with outstanding NIR-II imaging performance, excellent photothermal conversion efficiency (52.5%) under 808 nm laser irradiation, and good photostability. Fluorescence imaging experiments have consistently shown that P@TP can image tiny blood vessels in mice, enrich effectively in the tumor region, and maintain a relatively stable NIR-II fluorescence signal in the tumor area for a long time up to 60 h. In vivo photothermal therapy has a highly significant anticancer effect without tumor recurrence, demonstrating the apparent advantages of P@TP as a NIR nanotheranostic platform in NIR-II imaging-guided photothermal therapy.
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Nanopartículas , Neoplasias , Animales , Electrones , Colorantes Fluorescentes/química , Ratones , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Péptidos , Fototerapia , Nanomedicina Teranóstica/métodosRESUMEN
Most NIR-II fluorescent dyes, especially polymethine cyanine, face the inevitable self-quenching phenomenon in an aqueous solution. This unacceptable property has severely limited their application in high-resolution biological imaging. Here, a NIR-II macromolecular probe (MPAE) is synthesized through the structure modification of molecule probe and the covalent coupling of an amphiphilic polypeptide, which presents considerable biocompatibility and negligible systemic side effect. The molecule probe's stereo structure and the polymer's conjugation could effectively prevent the π-π stacking, thereby exhibiting excellent quenching resistance in aqueous solutions (absolute QY = 0.178%). This remarkable feature endows it with deeper tissue penetration than the clinically used indocyanine green (ICG) and high contrast brightness at the tumor site for the NIR-II fluorescence imaging. Based on the effective accumulation of tumor sites and considerable photothermal conversion efficiency (40.07%), the MPAE-NPS presents superior antitumor efficiency on breast tumor-bearing mice under the 1064 nm irradiation without rebound or recurrence. All these outstanding performances reveal the great promise of MPAE-NPS in Nano-drug delivery and imaging-assisted photothermal therapy in the NIR-II window.
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Nanopartículas , Terapia Fototérmica , Animales , Línea Celular Tumoral , Colorantes Fluorescentes , Verde de Indocianina , Ratones , Imagen Óptica , FototerapiaRESUMEN
Buckwheat is one of the five main allergenic foods (eggs, milk, wheat, buckwheat, and peanuts). Oleosin is an important type of allergen in some allergic foods. However, although most diagnostic nut and seed extracts are defatted, some patients with food allergies may have false negative diagnostic results of oleosin in vitro. Recently, we found that the serum of buckwheat allergic patients responded strongly to an 18 kDa protein. Mass spectrometry analysis showed it is the oleosin protein family. We further purified and evaluated the allergenicity of this buckwheat oleosin-type allergen, which is involved in the formation of buckwheat oil bodies. The tartary buckwheat oleosin allergen was named Fag t 6, according to the WHO/IUIS Allergen Nomenclature Subcommittee criteria. The DNA sequence of tartary buckwheat oleosin was cloned. Dot blot and enzyme-linked immunosorbent assay (ELISA) showed half of the 20 buckwheat allergic patients' serum had strong reactivity with purified buckwheat Fag t 6. Circular dichroism experiment analysis of its thermal stability showed a Tm of 64.65 ± 0.65 °C. A buckwheat allergy showed possible cross-reaction with a wheat allergy. In summary, this study not only increases our understanding of buckwheat allergies and oil-soluble allergens in general, it may also be used to improve diagnostic tests for buckwheat allergies in the future.
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Fagopyrum , Hipersensibilidad a los Alimentos , Hipersensibilidad al Trigo , Alérgenos , Humanos , Proteínas de Plantas/genética , SemillasRESUMEN
UNLABELLED: The increasing incidence of hepatocellular carcinoma (HCC) is of great concern not only in the United States but throughout the world. Although sorafenib, a multikinase inhibitor with antiangiogenic and antiproliferative effects, currently sets the new standard for advanced HCC, tumor response rates are usually quite low. An understanding of the underlying mechanisms for sorafenib resistance is critical if outcomes are to be improved. In this study we tested the hypothesis that hypoxia caused by the antiangiogenic effects of sustained sorafenib therapy could induce sorafenib resistance as a cytoprotective adaptive response, thereby limiting sorafenib efficiency. We found that HCCs, clinically resistant to sorafenib, exhibit increased intratumor hypoxia compared with HCCs before treatment or HCCs sensitive to sorafenib. Hypoxia protected HCC cells against sorafenib and hypoxia-inducible factor 1 (HIF-1α) was required for the process. HCC cells acquired increased P-gp expression, enhanced glycolytic metabolism, and increased nuclear factor kappa B (NF-κB) activity under hypoxia. EF24, a molecule having structural similarity to curcumin, could synergistically enhance the antitumor effects of sorafenib and overcome sorafenib resistance through inhibiting HIF-1α by sequestering it in cytoplasm and promoting degradation by way of up-regulating Von Hippel-Lindau tumor suppressor (VHL). Furthermore, we found that sustained sorafenib therapy led to increased intratumor hypoxia, which was associated with sorafenib sensitivity in HCC subcutaneous mice tumor models. The combination of EF24 and sorafenib showed synergistically effects against metastasis both in vivo and in vitro. Synergistic tumor growth inhibition effects were also observed in subcutaneous and orthotopic hepatic tumors. CONCLUSION: Hypoxia induced by sustained sorafenib treatment confers sorafenib resistance to HCC through HIF-1α and NF-κB activation. EF24 overcomes sorafenib resistance through VHL-dependent HIF-1α degradation and NF-κB inactivation. EF24 in combination with sorafenib represents a promising strategy for HCC.