Hydrogel Microneedles Extracting Exosomes for Early Detection of Colorectal Cancer.

There are several methods for early diagnosis of tumors, such as detecting circulating tumor DNAs, detecting circulating tumor cells, or imaging with tumor-targeting contrast agents. However, these assays are time-consuming and may cause patient discomfort during the biopsy collecting process. Here, we develop a facile method for early diagnosis of tumors by extracting exosomes from interstitial fluid (ISF) using hydrogel microneedles (MNs). The hydrogel MNs expand in the skin to absorb the ISF, and the tumor exosomes contained in the ISF bind with the glypican-1 antibodies inside the hydrogel of MNs. After removing the hydrogel on the MNs, exosomes are separately purified from the ISF to analyze tumor-related biomarkers. Finally, colorectal cancer can be diagnosed by ELISA for the colorectal cancer-induced model mice. This noninvasive hydrogel MN system to obtain the exosome samples would play an important role in early cancer diagnosis.

Bimetallic Hyaluronate-Modified Au@Pt Nanoparticles for Noninvasive Photoacoustic Imaging and Photothermal Therapy of Skin Cancer.

Although spherical gold (Au) nanoparticles have remarkable photothermal conversion efficiency and photostability, their weak absorption in the near-infrared (NIR) region and poor penetration into deep tissues have limited further applications to NIR light-mediated photoacoustic (PA) imaging and noninvasive photothermal cancer therapy. Here, we developed bimetallic hyaluronate-modified Au-platinum (HA-Au@Pt) nanoparticles for noninvasive cancer theranostics by NIR light-mediated PA imaging and photothermal therapy (PTT). The growth of Pt nanodots on the surface of spherical Au nanoparticles enhanced the absorbance in the NIR region and broadened the absorption bandwidth of HA-Au@Pt nanoparticles by the surface plasmon resonance (SPR) coupling effect. In addition, HA facilitated the transdermal delivery of HA-Au@Pt nanoparticles through the skin barrier and enabled clear tumor-targeted PA imaging. Compared to conventional PTT via injection, HA-Au@Pt nanoparticles were noninvasively delivered into deep tumor tissues and completely ablated the targeted tumor tissues by NIR light irradiation. Taken together, we could confirm the feasibility of HA-Au@Pt nanoparticles as a NIR light-mediated biophotonic agent for noninvasive skin cancer theranostics.

Radiative and Non-Radiative Decay Pathways in Carbon Nanodots toward Bioimaging and Photodynamic Therapy.

The origin and classification of energy states, as well as the electronic transitions and energy transfers associated with them, have been recognized as critical factors for understanding the optical properties of carbon nanodots (CNDs). Herein, we report the synthesis of CNDs in an optimized process that allows low-temperature carbonization using ethanolamine as the major precursor and citric acid as an additive. The results obtained herein suggest that the energy states in our CNDs can be classified into four different types based on their chemical origin: carbogenic core states, surface defective states, molecular emissive states, and non-radiative trap states. Each energy state is associated with the occurrence of different types of emissions in the visible to near-infrared (NIR) range and the generation of reactive oxygen species (ROS). The potential pathways of radiative/non-radiative transitions in CNDs have been systematically studied using visible-to-NIR emission spectroscopy and fluorescence decay measurements. Furthermore, the bright photoluminescence and ROS generation of these CNDs render them suitable for in vitro imaging and photodynamic therapy applications. We believe that these new insights into the energy states of CNDs will result in significant improvements in other applications, such as photocatalysis and optoelectronics.

Dissolving microneedles delivering cancer cell membrane coated nanoparticles for cancer immunotherapy.

Recently, a variety of tumor vaccines and immune system stimulators such as toll-like receptor (TLR) agonists have been widely investigated for cancer immunotherapy via transdermal delivery. Despite these great research efforts, low efficiency and discomfort remain a huge technical hurdle for the development of immunotherapeutics. Here, we design a facile method to deliver drugs to the skin through microneedles (MNs) to stimulate the immune system in two ways. As one of the tumor vaccines, cancer cell membrane proteins can act as tumor-specific antigens that are presented to antigen presenting cells (APCs) to activate the immune system. In addition, a toll-like receptor 7 (TLR7) agonist of imiquimod (R837) can suppress cancer cell growth by inhibiting angiogenesis. Using poloxamer 407 (F127) as a nanocarrier, F127 nanoparticles (F127 NPs) are loaded with R837 and then coated with cancer cell membranes (M). These F127-R837@M NPs are loaded in rapidly dissolving MNs and delivered through the skin. MNs loaded with F127-R837@M NPs show significant inhibition of cancer cell growth in both prophylactic vaccination and antitumor immunotherapy in vivo. The dual immune system stimulating F127-R837@M NPs could be effectively used for cancer immunotherapy.

Biocompatible Organosilica Nanoparticles with Self-Encapsulated Phenyl Motifs for Effective UV Protection.

With increasing ozone depletion, ultraviolet (UV) exposure from sunlight has become a significant health risk. Although commercially available sun protectants provide reasonable protection, they have limitations in terms of safety and aesthetics. Here, we have developed biocompatible and biodegradable sunscreens by facile synthesis of organosilica nanoparticles (o-SNPs) with self-encapsulated phenyl motifs using phenylsilane precursors. The physical structure of o-SNPs is elaborately controlled such that they are large enough to reflect UVA but small enough to be imperceptible when applied on the skin. The chemically attached phenyl motifs to o-SNPs facilitate filtering UVB via their delocalized π-orbitals. The o-SNPs generate a negligible amount of reactive oxygen species under UV exposure. Ex vivo two-photon microscopy reveals that the o-SNPs tend to adhere to the outer layers of skin without further intradermal penetration, resulting in less skin irritation. In vivo UV protection tests confirmed the excellent sunscreen effect of o-SNPs compared with conventional organic and inorganic UV filters.

Biodegradable Microneedle Patch Delivering Antigenic Peptide-Hyaluronate Conjugate for Cancer Immunotherapy.

Antigenic peptide-delivery systems have been extensively investigated to harness the immune system for cancer therapy. Cytotoxic T-cell epitope peptide can induce an antigen-specific CD8+ T-cell response, which subsequently inhibits the growth of antigen-bearing tumors. However, there are only a few facile tailored delivery systems of antigenic peptide for effective cancer immunotherapy. Here, we developed a biodegradable microneedle patch delivering a hyaluronate (HA)-antigenic peptide conjugate for prophylactic cancer immunotherapy. Cytotoxic T-cell epitope peptide (SIINFEKL) was conjugated to HA, which was loaded into a biodegradable HA microneedle (MN) patch to efficiently deliver an antigen to the immune system in the skin. HA could act as a transdermal vaccine carrier eliciting strong immune responses by the efficient stimulation of immunocompetent cells. The HA-SIINFEKL conjugates loaded into biodegradable MNs were localized near the MN administration site, exhibiting long-term residence for more than 24 h post-administration. Remarkably, a single transdermal vaccination with the MN patch containing HA-SIINFEKL conjugates resulted in a statistically significant inhibition of tumor growth in B16 melanoma model mice by enhancing antigen-specific cytotoxic T-cell responses.

Defect-Induced Fluorescence of Silica Nanoparticles for Bioimaging Applications.

With biocompatibility, biodegradability, and high functionality, silica nanoparticles (SNPs) have been widely investigated for various biomedical applications. However, lack of optical fluorescence has limited the application of SNPs as a degradable imaging agent. Here, we hydrothermally synthesized fluorescent SNPs by artificially generating optically active defect centers using tetraethyl orthosilicate and (3-aminopropyl)trimethoxysilane. The synthesized SNPs demonstrated strong blue photoluminescence originating from the dioxasilyrane (=Si(O2)) and silylene (=Si:) defect centers with the aid of aminopropyl groups. Furthermore, phosphorescence was observed at 459 nm, indicating the presence of silylene in SNPs. Finally, these SNPs have been successfully utilized as a fluorescent probe for bioimaging of normal, cancer, and macrophage cells.

Prevalence of floppy eyelid syndrome in obstructive sleep apnea-hypopnea syndrome.

OBJECTIVES: To determine the prevalence of floppy eyelid syndrome (FES) in obstructive sleep apnea-hypopnea syndrome (OSAHS) and to develop a method to measure eyelid laxity. DESIGN: Masked cross-sectional (prevalence) study examining patients referred to the Mayo Sleep Disorders Center. PARTICIPANTS AND/OR CONTROLS: Fifty-nine subjects were examined before undergoing polysomnography. Forty-four subjects had OSAHS, and 15 did not have it. TESTING: Subjects underwent slit-lamp examination and eyelid laxity measurements, followed by polysomnography. MAIN OUTCOME MEASURES: Presence of FES as defined by subjectively easy eyelid eversion, tarsal papillary conjunctivitis, and lash ptosis; force required to displace the upper lid 5 mm, as measured by a strain gauge device; number of apnea or hypopnea episodes per hour (apnea-hypopnea index [AHI]); presence of OSAHS, as defined by an AHI of > or =5; and abnormalities on electrocardiography. RESULTS: One patient with OSAHS was found to have FES, yielding a prevalence of 2.3% (95% confidence interval [CI]: 0.1%-12.0%). One patient was referred to the Sleep Disorders Center due to a diagnosis of FES; if this patient were included, the prevalence would be 4.5% (95% CI: 0.5%-15.1%). Subjectively easy lid eversion was more common in OSAHS patients than in non-OSAHS patients. When adjusted for age and body mass index, there was a trend for association between subjectively easy lid eversion and OSAHS, but this did not reach statistical significance. Subjectively easy lid eversion was associated with AHI. Force required to displace the upper lid 5 mm was lower in lids with subjectively easy eversion, but was not associated with OSAHS or AHI. Intraclass correlation among 3 strain gauge measurements was good for both right (82%) and left (83%) lids. There were no statistically significant differences in frequency of electrocardiographic abnormalities among the various groups. CONCLUSIONS: The prevalence of FES among OSAHS patients is low. Patients with subjectively easy upper lid eversion are at risk for OSAHS. By recognizing the potential for OSAHS in these patients, the ophthalmologist may play an important role in initiating their evaluation and treatment.