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Despite burgeoning development of nanoplatform made in the past few years, it remains a challenge to produce drug nanocarrier that enables requested on/off drug release. Thus, this study aimed to develop an ideal near-infrared light-triggered smart nanocarrier for targeted imaging-guided treatment of cancer that tactfully integrated photothermal therapy with chemotherapy to accurately control drug release time and dosage. Methods: This delivery system was composed of Ag2S QD coating with dendritic mesoporous silica (DMSN), which acted as nanocarrier of doxorubicin localized inside pores. To provide the nanocarrier with controlled release capability, a polypeptide-engineered that structure was reversible to photothermal effect of Ag2S QD, was covalently grafted to the external surface of drug-loaded DMSN. Results: This nanocarrier with the size of 40~60 nm had satisfactory biocompatibility and photothermal conversion efficiency up to 28.35%. Due to acidity-triggered charge reversal of polypeptide, which significantly extended circulation time and improved targeting ability, fluorescence and photoacoustic signals were still obvious at tumor site post-24 h by tail vein injection and chemo-photothermal synergistic therapy obviously enhanced antitumor efficacy. Mild PTT with multiple short-term exposures not only reduced the side effect of overdose drug but also avoided skin damage caused by long-term irradiation. Conclusion: By adjusting irradiation time and on/off cycle, multiple small amount local drug release reduced the side effect of overdose drug and skin damage. This novel approach provided an ideal near-infrared light-triggered nanocarrier with accurate control of area, time, and especially dosage.

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Ag2S quantum dots have received extensive attention as theranostic agents for second near-infrared (NIR-II) fluorescence and photoacoustic dual-mode imaging, and photothermal therapy. However, it is still greatly challenging to synthesize Ag2S quantum dots using aqueous synthesis. In this study, genetically engineered polypeptide-capped Ag2S quantum dots were successfully synthesized. Three cysteines were integrated to the C-terminal and N-terminal of RGDPC10A to enhance the stability and brightness of the synthesized Ag2S quantum dots. The RGDPC10A-capped Ag2S quantum dots exhibited excellent stability, outstanding resistance to photobleaching, and a superior quantum yield of up to 3.78% in the NIR-II biological window. The in vitro and in vivo results showed that the RGDPC10A-capped Ag2S quantum dots possessed typical NIR-II fluorescence, photoacoustic imaging, and photothermal therapeutic effectiveness against tumors. Moreover, the results of toxicity assays suggested that the RGDPC10A-capped Ag2S quantum dots have negligible long-term toxicity. These findings open up the possibility for synthesizing theranostic agents by using this aqueous method.

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By integrating the characteristics of each therapy modality and material chemistry, a multitherapy modality is put forward: tumor starvation triggered synergism with sensitized chemotherapy. Following starvation-induced amplification of pathological abnormalities in tumors, chemotherapy is arranged to be locally activated and accurately reinforced to perfect multitherapy synergism from spatial and temporal perspectives. To this end, glucose oxidase (GOD) and a hypoxic prodrug of tirapazamine (TPZ) are loaded in acidity-decomposable calcium carbonate (CaCO3 ) nanoparticles concurrently tethered by hyaluronic acid. This hybrid nanotherapeutic shows a strong tendency to accumulate in tumors postinjection due to the cooperation between passive and active targeting mechanisms. The GOD-driven oxidation reaction deprives tumors of glucose for starvation therapy and concomitantly induces tumorous abnormality amplifications including elevated acidity and exacerbated hypoxia. Programmatically, the acidity amplification causes CaCO3 decomposition, offering not only spatial control over the liberation of embedded TPZ just within tumors but also the temporal control over timely chemotherapy initiation to match the occurrence of hypoxia amplification and thus benefiting perfect synergism between starvation therapy and chemotherapy.

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BACKGROUND: Ag2S has the characteristics of conventional quantum dot such as broad excitation spectrum, narrow emission spectrum, long fluorescence lifetime, strong anti-bleaching ability, and other optical properties. Moreover, since its fluorescence emission is located in the NIR-II region, has stronger penetrating ability for tissue. Ag2S quantum dot has strong absorption during the visible and NIR regions, it has good photothermal and photoacoustic response under certain wavelength excitation. RESULTS: 200 nm aqueous probe Ag2S@DSPE-PEG2000-FA (Ag2S@DP-FA) with good dispersibility and stability was prepared by coating hydrophobic Ag2S with the mixture of folic acid (FA) modified DSPE-PEG2000 (DP) and other polymers, it was found the probe had good fluorescent, photoacoustic and photothermal responses, and a low cell cytotoxicity at 50 µg/mL Ag concentration. Blood biochemical analysis, liver enzyme and tissue histopathological test showed that no significant influence was observed on blood and organs within 15 days after injection of the probe. In vivo and in vitro fluorescence and photoacoustic imaging of the probe further demonstrated that the Ag2S@DP-FA probe had good active targeting ability for tumor. In vivo and in vitro photothermal therapy experiments confirmed that the probe also had good ability of killing tumor by photothermal. CONCLUSIONS: Ag2S@DP-FA was a safe, integrated diagnosis and treatment probe with multi-mode imaging, photothermal therapy and active targeting ability, which had a great application prospect in the early diagnosis and treatment of tumor.

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In this study, an oil-soluble Ag2S quantum dot (QD) was synthesized through thermal decomposition using the single-source precursor method, and Pluronic F127 (PF127), a triblock copolymer functionalized with folic acid (FA), was deposited on the surface of the QD, then a water-soluble PF127-FA@Ag2S nanoprobe with targeting ability was fabricated. The as-prepared PF127-FA@Ag2S exhibited spheroidal morphology and high dispersibility, with average diameters of 115 ± 20.7 nm (as observed by transmission electron microscopy). No obvious toxicity of the PF127-FA@Ag2S nanoprobe was found in standard 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and colony-formation assay, indicating good biocompatibility and safety. The resulting PF127-FA@Ag2S exhibited excellent stability between 4 °C-40 °C. Additionally, the capacity of the tumor cell-targeting high contrast enhanced photoacoustic imaging of PF127-FA@Ag2S was verified in comparison with A547 and HeLa cells. In other words, the excellent properties of PF127-FA@Ag2S show great potential in further research for targeting and photoacoustic imaging.

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The accurate treatment of tumors with the help of multimodality imaging is of great significance. Herein, a novel multifunctional probe combining active targeted fluorescent imaging (FL)/photoacoustic imaging (PA) and chemo-photothermal therapy for tumors has been designed. Targeting molecule folate (FA) modified graphene oxide (GO) was used to coat core-shell silver sulfide@mesoporous silica (QD@Si) while antitumoral doxorubicin (DOX) was loaded in mesoporous channels by electrostatic adhesion, and a delivery system (QD@Si-D/GO-FA) for active targeted dual-mode imaging and synergistic chemo-photothermal for tumors was successfully obtained. Experiments showed the cell survival rate was 76.3 ± 4.6% when the probe concentration reached 0.5 mg mL-1, and demonstrated that the probe had good biocompatibility. In vivo and in vitro results indicated that this probe could be used for active targeted FL/PA for tumors with overexpressed FA receptors. The temperature of the tumor rose to 63.5 °C under laser irradiation, and the tumor could be killed more effectively after combination with chemotherapy, which was caused by exfoliation of GO from QD@Si-D/GO-FA after irradiation. These results showed that the probe had great potential for application in oncology and is expected to provide evidence for early diagnosis and treatment of tumors.

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Safe multifunctional nanoplatforms that have multiple therapeutic functions integrated with imaging capabilities are highly desired for biomedical applications. In this paper, targeted chemo-photothermal synergistic therapy and photoacoustic/computed tomography imaging of tumors were achieved by one novel multifunctional nanoprobe (GMS/DOX@SLB-FA); it was composed of a gold nanostar core and a doxorubicin (DOX)-loaded mesoporous silica shell (GMS), which was coated with a folic acid (FA)-modified thermosensitively supported lipid bilayer (SLB-FA) as a gatekeeper. The multifunctional probe had perfect dispersion and stability; 2.1 nm mesoporous pores and 208 nm hydration particle sizes were obtained. In vitro studies indicated that the drug-loaded probe had excellent ability to control the release of DOX, with 71.98 ± 2.52% cumulative release after laser irradiation, which was significantly higher than that of unirradiated control group. A survival rate of 72.75 ± 4.37% of HeLa cells at 57.75 µg/mL probe also demonstrated the low cytotoxicity of the targeted probe. Both in vitro and in vivo results showed that the probe could achieve targeted photoacoustic imaging of tumors because of the fact that the FA-modified probe could specifically recognize the overexpressed FA receptors on tumor cells; meanwhile, the probe could also achieve the chemo-photothermal synergistic therapy of tumors through controlling the drug release from mesoporous channels by a near-infrared laser. Therefore, the probe had great potential in the early diagnosis and treatment of cancer.