A Binary Functional Substrate for Enrichment and Ultrasensitive SERS Spectroscopic Detection of Folic Acid Using Graphene Oxide/Ag Nanoparticle Hybrids

Herein graphene oxide/Ag nanoparticle hybrids (GO/PDDA/AgNPs) were fabricated according to a self-assembly procedure. Using the obtained GO/PDDA/AgNPs as SERS substrates, an ultrasensitive and label-free detection of folic acid in water and serum was demonstrated based on the inherent SERS spectra of folic acid. The modified graphene oxide exhibited strong enrichment of folic acid due to the electrostatic interaction, and the self-assembled Ag nanoparticles greatly enhanced the SERS spectra of folic acid, both of which led to an ultrahigh sensitivity. Therefore, although the SERS enhancement of p-ATP on GO/PDDA/AgNPs was weaker than that on Ag nanoparticles, the SERS signals of folic acid on GO/PDDA/AgNPs were much stronger than that on Ag nanoparticles. To improve the detection, the concentration of GO/PDDA/AgNPs was optimized to reduce background of the graphene oxide. The SERS spectra of the folic acid showed that the minimum detected concentration of folic acid in water was as low as 9 nM with a linear response range from 9 to 180 nM. To estimate the feasibility of the detection method based on GO/PDDA/AgNPs for the practical applications, diluted serum containing different concentrations of folic acid was taken as real samples. It was established that the sensitivity and the linear range for the folic acid in serum were comparable to that in water. This ultrasensitive and label-free SERS detection of folic acid based on GO/PDDA/AgNPs offers great potential for practical applications of medicine and biotechnology

Additional file 3: of Epigenetic biomarker screening by FLIM-FRET for combination therapy in ER+ breast cancer

Figure S3. Reduced FRET efficiency between ERα and histone acetylation marker after 80 μM anacardic acid treatment for 24 h. (A) Typical donor channel FLIM images of MCF7 cells treated with and without anacardic acid. Only fluorescence lifetime information was shown. Typical single cell lifetime histogram (B) without and (C) with anacardic acid treatment. Fluorescence lifetime histogram of ERα-ALEXA488 only (red); co-immunostaining of ERα-ALEXA488 and H4K12ac-ALEXA546 (blue) are shown parallel for comparison. A binning of 7 and 100 counts as threshold for background was applied for analysis. (D) TCSPC graph of typical single cell lifetime decay with ERα-H4K12ac interaction used for analysis. (E) FRET efficiency reduces non-specific level after anacardic acid exposure between ERα and H4K12ac/H3K27ac. n~20 cells. Scale bar = 5 μm. (PDF 433 kb

Additional file 1: of Epigenetic biomarker screening by FLIM-FRET for combination therapy in ER+ breast cancer

Figure S1. Screening ER-associated epigenetic markers with FLIM-FRET. (A) Representative raw FLIM images from the donor channel. (B) Corresponding normalized lifetime histogram of FLIM image in Fig. 1c from patient tissue array. Scale bar = 10 μM. (PDF 130 kb

A Simple Route for the Synthesis of Morphology-Controlled and SERS-Active Ag Dendrites with Near-Infrared Absorption

Herein we developed a simple and low-cost route for morphology-controllable synthesis of Ag dendrites based on a facile wet chemical route. The morphology of Ag dendrites was tunable by changing the concentration of capping reagent PVP. It was demonstrated that for higher concentrations of PVP, smaller Ag dendrites with shorter and smoother branches were obtained, while the ratio of the length of the branches to the body diameter of the Ag dendrites (L/D) became lower. It was also shown that the concentration of added AgNO3 was very important for the formation of Ag dendrites. The presented method is amenable for extension to large-scale synthesis of Ag dendrites. The prepared Ag dendrites exhibited strong near-infrared absorption proved by UV–visible spectra. Using p-ATP as a probe molecule, the SERS activity of prepared Ag dendrites was estimated. Based on the apparent enhancement factor and the measured diameter and L/D of the morphology-controlled Ag dendrites, the relation between the morphology and the SERS activity of Ag dendrites was investigated. It was shown that the smaller Ag dendrites with a lower L/D exhibited larger SERS activity

Additional file 6: of Epigenetic biomarker screening by FLIM-FRET for combination therapy in ER+ breast cancer

Figure S6. Co-presence of ERα and H4K12ac near ERE sites. qRT-PCR experiments were conducted with mice tumor for ERα and H4K12ac occupancy near TFF1/GREB1 ERE in CHIP samples. n = 2. mean ± s.d. (PDF 221 kb

Oxygen Nanobubbles-Embedded Hydrogel as Wound Dressing to Accelerate Healing

Herein, we propose an oxygen nanobubbles-embedded hydrogel (ONB-G) with carbopol for oxygenation of wounds to accelerate the wound healing process. We integrate carbopol, hydrogel, and dextran-based oxygen nanobubbles (ONBs) to prepare ONB-G where ONBs can hold and release oxygen to accelerate wound healing. Oxygen release tests showed that the proposed ONB-G could encapsulate oxygen in the hydrogels for up to 34 days; meanwhile, fluorescence studies indicated that the ONB-G could maintain high oxygen levels for up to 4 weeks. The effect of carbopol concentration on the oxygen release capacity and rheological features of the ONB-G were also investigated along with the sterility of ONB-G. HDFa cell-based studies were first conducted to evaluate the viability, proliferation, and revival of cells in hypoxia. Scratch assay and mRNA expression studies indicated the potential benefit for wound closure. Histological evaluation of tissues with a pig model with incision and punch wounds showed that treatment with ONB-G exhibited improved healing compared with hydrogel without ONBs or treated without the gel. Our studies show that dextran-shell ONBs embedded in a gel (ONB-G) have the potential to accelerate wound healing, given its oxygen-holding capacity and release properties

Additional file 4: of Epigenetic biomarker screening by FLIM-FRET for combination therapy in ER+ breast cancer

Figure S4. Non-specific HATi on screened histone acetylation marker shows minimal therapeutic effect. MTT cell viability assay after 48 h treatment of (A) MB3 and (B) CPTH2 at various concentrations. Date shown as mean ± s.d., n = 3. (C) H4K12ac quantification after 24 h treatment with 300 μM of either CPTH2 or MB3. n = 3, shown in mean ± s.d. (PDF 299 kb

Multifunctional Oxygenated Particles for Targeted Cancer Drug Delivery and Evaluation with Darkfield Hyperspectral Imaging

We propose a novel multifunctional nanocarrier system for targeted drug delivery for lung cancer theranostics. Oxygenated particles (OPs) synthesized with an oxygen-encapsulating carboxymethyl cellulose shell were used as a platform to deliver oxygen to the hypoxic tumor microenvironment. The OPs synthesized could also be conjugated with ligands (e.g., antibodies) to target cancer cells expressing the corresponding antigens to deliver a drug, doxorubicin. In vitro testing of functionalized OPs showed increased efficacy of doxorubicin against the proliferation of lung cancer cells. Both confocal fluorescence imaging and darkfield microscopy hyperspectral imaging validated the OP complex and its efficient targeting of specific cells to deliver the therapeutic. The nanocarrier platform developed can also serve as a diagnostic imaging reagent as demonstrated by darkfield microscopy. Results show that the theranostic OPs developed with multifunctional modalities enabled targeted drug delivery with improved efficacy and tracking of drug delivery vehicles by imaging

Additional file 5: of Epigenetic biomarker screening by FLIM-FRET for combination therapy in ER+ breast cancer

Figure S5. Combination treatment based on FLIM-FRET screening. (A) MTT assays show treatment of 10 μM tamoxifen and 100 μM anacardic acid for 24. n = 3, *p < 0.05, **p < 0.01. (B) MTT assay shows treatment of 10 μM tamoxifen and 50 μM anacardic acid for 48 h from 2 independent assays (C) Combination treatment of TAM (4 mg kg-1) with AA (0.3 mg kg-1) did not show enhanced treatment effect in mice MCF7 cell xenograft. Mean ± s.e.m., n = 5. (D) qRT-PCR of TFF1, CCND1, and GREB1 genes from three different mice tumors. For each gene, left to right as control, TAM 4 mg kg-1, AA 1 mg kg-1, and TAM 4 mg kg-1 + AA 1 mg kg-1. n = 3 (PDF 294 kb

Additional file 2: of Epigenetic biomarker screening by FLIM-FRET for combination therapy in ER+ breast cancer

Figure S2. Anacardic acid inhibits histone acetylation level. (A) MTT cell viability assay of MCF7 cells after 48 h treatment of anacardic acid at various concentrations, n > 5. (B) MTT cell viability assay of T47D cells after 48 h of treatment with 100 μM anacardic acid and 10 μM tamoxifen, n = 3. (C) Global H3k27ac quantification of combination treatment of 10 μM tamoxifen and 50 μM anacardic acid after 24 h treatment. (D) H4K12ac quantification from mice xenograft, TAM 4 mg kg-1, AA 1 mg kg-1, and TAM 4 mg kg-1 + AA 1 mg kg-1, n = 3. (E) Normalized H4K12ac quantification of both MCF7 cell and T47D cells after 24 h and 48 h of treatment with 100 μM anacardic acid, n = 3. (F) Western blot quantification of H4K12ac level. Histone protein from 100 μM AA treated MCF7 cell for 24 h. Data shown as mean ± s.d. *p < 0.05, **p < 0.01 compared with control group. (PDF 512 kb