Visualization of photothermal therapy by semiconducting polymer dots mediated photoacoustic detection in NIR II.

Visualization of photothermal therapy mediated by photothermal transduction agents (PTAs) is important to promote individual treatment of patients with low side effects. Photoacoustic detection has emerged as a promising noninvasive method for the visualization of PTAs distribution but still has limitations in temperature measurement, including poor measurement accuracy and low tissue penetration depth. In this study, we developed biocompatible semiconducting polymer dots (SPD) for in situ coupling of photothermal and photoacoustic detection in the near-infrared II window. SPD has dual photostability under pulsed laser and continuous-wave laser irradiation with a photothermal conversion efficiency of 42.77%. Meanwhile, a strong correlation between the photoacoustic signal and the actual temperature of SPD can be observed. The standard deviation of SPD-mediated photoacoustic thermometry can reach 0.13 °C when the penetration depth of gelatin phantom is 9.49 mm. Preliminary experimental results in vivo show that SPD-mediated photoacoustic signal has a high signal-to-noise ratio, as well as good performance in temperature response and tumor enrichment. Such a study not only offers a new nanomaterial for the visualization of photothermal therapy but will also promote the theranostic platform for clinical applications.

[Effects of different hypoxic concentrations on biological characteristics of human dental pulp stem cells in vitro].

PURPOSE: To investigate the effects of different hypoxic concentrations on biological characteristics of human dental pulp stem cells in vitro. METHODS: Impacted mandibular third molars were extracted from healthy individuals, and the dental pulp stem cells were cultured by tissue block enzyme digestion. Cells cultured under the conditions of 3%, 5% and 21% oxygen concentration for 7 days were set as 3% hypoxia group, 5% hypoxia group, and 21% nomoxia group, respectively. Flow cytometry was used to detect cell surface markers, cell cycle and apoptosis. Cell proliferation was measured by CCK-8 method. Transwell chamber assay was used to detect migration ability. Statistical analysis was completed by SPSS 20.0 software package. RESULTS: The expression rates of CD44, CD29 and D73 of the subculture cells were 97.25%, 99.36% and 99.60%, respectively. The proliferation ability of dental pulp stem cells was the strongest in 5% hypoxia group, and weakest in 3% hypoxia group, with significant difference(P<0.05). The apoptosis rate had no significant difference among various concentrations of oxygen(P>0.05). Compared with 21% nomoxia group, the proportion of dental pulp stem cells in G1 phase was significantly lower than that in 3% hypoxia group and 5% hypoxia group(P<0.05), and cell in S phase was significantly higher than that in 3% hypoxia group and 5% hypoxia group(P<0.05). The migration ability was the strongest in 3% hypoxia group, and weakest in 21% nomoxia group, with significant difference(P<0.05). CONCLUSIONS: Different concentrations of hypoxia have great influence on the morphology, proliferation, migration and cell cycle of human dental pulp stem cells in vitro with little impact on cell apoptosis.

Corneal Lamb wave imaging for quantitative assessment of collagen cross-linking treatment based on comb-push ultrasound shear elastography.

Keratoconus, a serious corneal disorder, often causes highly irregular astigmatism and different degrees of visual impairment. Riboflavin/UVA corneal collagen cross-linking(CXL) is currently approved for effective treatment of keratoconus by enhancing the mechanical strength of collagen fibers in the cornea. However, few methods are capable of quantitatively and non-destructively assessing the mechanical properties of the cornea before and after CXL treatments. This study developed a corneal viscoelasticity imaging method based on comb-push ultrasound shear elastography (CUSE) and implemented this method on a Verasonics™ Vantage 256 ultrasound open system with a high-frequency linear array ultrasound transducer. Push beams were generated by three teeth each consisting of 10 elements (working frequency = 10.41 MHz) for inducing Lamb wave propagation in the cornea, and then the system immediately switched to the plane wave imaging mode using 60 elements in the middle (working frequency = 18 MHz). This method can provide a high-resolution 2D Lamb wave velocity image overlapping with a B-mode image as well as quantitative viscoelasticity estimation according to experimentally obtained phase velocity dispersion of Lamb waves. The validation experiments were performed on ex vivo porcine corneas, and the accuracy of elasticity estimation was verified by a tensile test. The results showed that the shear elasticity increased and the viscosity decreased after CXL treatment. The shear elasticity results (reported as mean ±â€¯standard deviation) of one control group with no CXL treatment and three CXL-treated groups named as 10 min, 30 min, and 60 min groups according to UV irradiation time were 14.62 ±â€¯3.38 kPa, 49.47 ±â€¯3.63 kPa, 116.54 ±â€¯23.99 kPa, and 197.89 ±â€¯39.64 kPa, respectively, which was in agreement with the results of tensile tests. The ultrasound safety measurement indicated that this method could have acceptable safety, but further to ocular tissue and vision function. The study demonstrated the possibility of using a commercial ultrasound system to obtain high-resolution images of corneal mechanical properties as well as the ability to quantify changes induced by CXL treatment. Therefore, the proposed method could serve as a helpful tool in the studies related in corneal biomechanics.

Facile fabrication of polyurethane microcapsules carriers for tracing cellular internalization and intracellular pH-triggered drug release.

A tailor-made traceable pH-sensitive drug delivery system based on polyurethane (PU) microcapsules was fabricated using a facile double-emulsion method containing 3,3'-dioctadecyloxacarbocyanine perchlorate, doxorubicin (DOX) and sodium bicarbonate (NaHCO3). When PU microcapsules were immersed in acidic media, NaHCO3 could react with the H+ to quickly produce CO2 bubbles to puncture the PU shell, resulting in rapid release of DOX to promptly reach the intracellular drug therapeutic threshold to kill cancer cells in a short period. Confocal laser scanning microscopic analysis showed that these traceable pH-sensitive drug carriers can be easily internalized by BGC 823 and Hela cells, and the loaded DOX can quickly release from PU microcapsules in the endo-/lysosomes to be mainly resided in cell nuclei. This traceable pH-sensitive drug carrier can achieve on-demand controlled release profiles for visualization of cancer therapy. Thus, it is a potential candidate for anticancer drug delivery system in advanced cancer therapy.

Enhanced delivery of paclitaxel liposomes using focused ultrasound with microbubbles for treating nude mice bearing intracranial glioblastoma xenografts.

Paclitaxel liposomes (PTX-LIPO) are a clinically promising antineoplastic drug formulation for the treatment of various extracranial cancers, excluding glioblastoma. A main reason for this is the presence of the blood-brain barrier (BBB) or blood-tumor barrier (BTB), preventing liposomal drugs from crossing at a therapeutically meaningful level. Focused ultrasound (FUS) in conjunction with microbubbles (MBs) has been suggested in many studies to be an effective approach to increase the BBB or BTB permeability. In this study, we investigated the feasibility of enhancing the delivery of PTX-LIPO in intracranial glioblastoma-bearing nude mice using pulsed low-intensity FUS exposure in the presence of MBs. Our results showed that the delivery efficiency of PTX-LIPO could be effectively improved in terms of the penetration of both the BBB in vitro and BTB in vivo by pulsed FUS sonication with a 10 ms pulse length and 1 Hz pulse repetition frequency at 0.64 MPa peak-rarefactional pressure in the presence of MBs. Quantitative analysis showed that a 2-fold higher drug concentration had accumulated in the glioblastoma 3 h after FUS treatment, with 7.20±1.18 µg PTX per g glioma tissue. Longitudinal magnetic resonance imaging analysis illustrated that the intracranial glioblastoma progression in nude mice treated with PTX-LIPO delivered via FUS with MBs was suppressed consistently for 4 weeks compared to the untreated group. The medium survival time of these tumor-bearing nude mice was significantly prolonged by 20.8%, compared to the untreated nude mice. Immunohistochemical analysis further confirmed the antiproliferation effect and cell apoptosis induction. Our study demonstrated that noninvasive low-intensity FUS with MBs can be used as an effective approach to deliver PTX-LIPO in order to improve their chemotherapy efficacy toward glioblastoma.

A new AIE multi-block polyurethane copolymer material for subcellular microfilament imaging in living cells.

A multi-block fluorescent amphiphilic polyurethane copolymer (TPE-PU), self-assembling into hairy, water-soluble micelles, is used as a subcellular microfilament probe in living cells.

Enhanced Afterglow Performance of Persistent Luminescence Implants for Efficient Repeatable Photodynamic Therapy.

Persistent luminescence nanoparticles (PLNPs) have been used for bioimaging without autofluorescence background interference, but the poor afterglow performance impedes their further applications in cancer therapy. To overcome the Achilles' heel of PLNPs, herein we report the construction of injectable persistent luminescence implants (denoted as PL implants) as a built-in excitation source for efficient repeatable photodynamic therapy (PDT). The injectable ZGC (ZnGa1.996O4:Cr0.004) PL implants were prepared by dissolving ZGC PLNPs in poly(lactic-co-glycolic acid)/N-methylpyrrolidone oleosol, which demonstrated much stronger persistent luminescence (PersL) intensity and longer PersL lifetime than that of ZGC PLNPs both in vitro and in vivo. More importantly, the intratumorally fixed ZGC PL implants can serve as a built-in excitation source for repeatable light emitting diode (LED) and PersL-excited PDT upon and after periodic LED irradiation, which leads to the overall improvement of therapeutic effectiveness for efficient tumor growth suppression. This work represents efficient repeatable PDT based on the injectable yet periodically rechargeable ZGC PL implants.

Core-Satellite Polydopamine-Gadolinium-Metallofullerene Nanotheranostics for Multimodal Imaging Guided Combination Cancer Therapy.

Integration of magnetic resonance imaging (MRI) and other imaging modalities is promising to furnish complementary information for accurate cancer diagnosis and imaging-guided therapy. However, most gadolinium (Gd)-chelator MR contrast agents are limited by their relatively low relaxivity and high risk of released-Gd-ions-associated toxicity. Herein, a radionuclide-64 Cu-labeled doxorubicin-loaded polydopamine (PDA)-gadolinium-metallofullerene core-satellite nanotheranostic agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission tomography (PET) multimodal imaging-guided combination cancer therapy. In this system, the near-infrared (NIR)-absorbing PDA acts as a platform for the assembly of different moieties; Gd3 N@C80 , a kind of gadolinium metallofullerene with three Gd ions in one carbon cage, acts as a satellite anchoring on the surface of PDA. The as-prepared CDPGM NPs show good biocompatibility, strong NIR absorption, high relaxivity (r 1 = 14.06 mM-1 s-1 ), low risk of release of Gd ions, and NIR-triggered drug release. In vivo MR/PA/PET multimodal imaging confirms effective tumor accumulation of the CDPGM NPs. Moreover, upon NIR laser irradiation, the tumor is completely eliminated with combined chemo-photothermal therapy. These results suggest that the CDPGM NPs hold great promise for cancer theranostics.

Observing the temperature dependent transition of the GP2 peptide using terahertz spectroscopy.

The GP2 peptide is derived from the Human Epidermal growth factor Receptor 2 (HER2/nue), a marker protein for breast cancer present in saliva. In this paper we study the temperature dependent behavior of hydrated GP2 at terahertz frequencies and find that the peptide undergoes a dynamic transition between 200 and 220 K. By fitting suitable molecular models to the frequency response we determine the molecular processes involved above and below the transition temperature (T(D)). In particular, we show that below T(D) the dynamic transition is dominated by a simple harmonic vibration with a slow and temperature dependent relaxation time constant and that above T(D), the dynamic behavior is governed by two oscillators, one of which has a fast and temperature independent relaxation time constant and the other of which is a heavily damped oscillator with a slow and temperature dependent time constant. Furthermore a red shifting of the characteristic frequency of the damped oscillator was observed, confirming the presence of a non-harmonic vibration potential. Our measurements and modeling of GP2 highlight the unique capabilities of THz spectroscopy for protein characterization.