Light-Activatable Red Blood Cell Membrane-Camouflaged Dimeric Prodrug Nanoparticles for Synergistic Photodynamic/Chemotherapy.
ACS Nano. 2018 Jan 18;:
Authors: Pei Q, Hu X, Zheng X, Liu S, Li Y, Jing X, Xie Z
Biomimetic approach offers numerous opportunities to design therapeutic platforms with enhanced antitumor performance and biocompatibility. Herein we report a novel red blood cell membrane-camouflaged nanoparticle (RBC(M(TPC-PTX))) for synergistic chemo- and photodynamic therapy (PDT). Specifically, the inner core is mainly constructed by reactive oxygen species (ROS)-responsive PTX dimer (PTX2-TK) and photosensitizer 5,10,15,20-tetraphenylchlorin (TPC). In vitro experiments show that the prepared RBC(M(TPC-PTX)) is readily taken up into endosomes. Under appropriate light irradiation, the TPC can generate ROS, not only for PDT, but also for triggering PTX2-TK cleavage and on-demand PTX release for chemotherapy. In vivo results show that the coating of RBC membrane prolongs blood circulation and improves tumor accumulation. The combination of chemo- and photodynamic therapy enhances anticancer therapeutic activity and light-triggered drug release reduces systematic toxicity. All these unique characteristics render the described technology extremely promising for cancer treatment.
PMID: 29346736 [PubMed - as supplied by publisher]
CHRONIC CENTRAL SEROUS CHORIORETINOPATHY: Early and Late Morphological and Functional Changes After Verteporfin Photodynamic Therapy.
Retina. 2018 Jan 16;:
Authors: Iacono P, Tedeschi M, Boccassini B, Chiaravalloti A, Varano M, Parravano M
PURPOSE: To describe early and late morphological and functional changes in subjects receiving photodynamic therapy (PDT) for chronic central serous chorioretinopathy.
METHODS: Patients with chronic central serous chorioretinopathy were prospectively enrolled and received standard PDT. At the baseline examination, each subject underwent complete ophthalmological examination, including best-corrected visual acuity (BCVA) assessment, fluorescein angiography and indocyanine green angiography, spectral domain optical coherence tomography, and microperimetry. Spectral domain optical coherence tomography, microperimetry, and BCVA assessment were repeated in multiple sections over 7 days after PDT and at 1-, 3-, and 12-month intervals. Main outcome measures were: identification of early changes (1-week examination) in BCVA, retinal sensitivity, and spectral domain optical coherence tomography parameters and their influence on outcomes at the 1-year follow-up.
RESULTS: Three main patterns of early response to PDT were identified during the 1-week examination. The neurosensory retinal detachment most frequently decreased rapidly (12/19 pts), with complete resolution in 50% of cases. An increase in neurosensory retinal detachment height was registered in 16% (3/19) of cases, whereas in 21% (4/19), a large fluctuation in neurosensory retinal detachment was encountered. Best-corrected visual acuity declined significantly in 5/12 patients in the first group and was stable or improved in the remaining cases. Overall, retinal sensitivity diminished in 16/19 subjects, with a mean worsening of 2.56 dB (P = 0.0002). At the 12-month examination, final mean BCVA improved by 14.4 letters (P = 0.001) and a similar progressive recovery in the retinal sensitivity was observed (+2.69 dB, P = 0.0039). The neurosensory retinal detachment completely resolved in 18/19 (95%) cases, with a parallel significant reduction in central foveal choroidal thickness (P < 0.0001).
CONCLUSION: Three patterns of early response to standard PDT can be identified. Although an early and abrupt reduction in BCVA and retinal sensitivity after treatment is possible, this does not compromise a final improvement in visual functions.
PMID: 29346241 [PubMed - as supplied by publisher]
Two-Photon-Excited Silica and Organosilica Nanoparticles for Spatiotemporal Cancer Treatment.
Adv Healthc Mater. 2018 Jan 18;:
Authors: Croissant JG, Zink JI, Raehm L, Durand JO
Coherent two-photon-excited (TPE) therapy in the near-infrared (NIR) provides safer cancer treatments than current therapies lacking spatial and temporal selectivities because it is characterized by a 3D spatial resolution of 1 µm3 and very low scattering. In this review, the principle of TPE and its significance in combination with organosilica nanoparticles (NPs) are introduced and then studies involving the design of pioneering TPE-NIR organosilica nanomaterials are discussed for bioimaging, drug delivery, and photodynamic therapy. Organosilica nanoparticles and their rich and well-established chemistry, tunable composition, porosity, size, and morphology provide ideal platforms for minimal side-effect therapies via TPE-NIR. Mesoporous silica and organosilica nanoparticles endowed with high surface areas can be functionalized to carry hydrophobic and biologically unstable two-photon absorbers for drug delivery and diagnosis. Currently, most light-actuated clinical therapeutic applications with NPs involve photodynamic therapy by singlet oxygen generation, but low photosensitizing efficiencies, tumor resistance, and lack of spatial resolution limit their applicability. On the contrary, higher photosensitizing yields, versatile therapies, and a unique spatial resolution are available with engineered two-photon-sensitive organosilica particles that selectively impact tumors while healthy tissues remain untouched. Patients suffering pathologies such as retinoblastoma, breast, and skin cancers will greatly benefit from TPE-NIR ultrasensitive diagnosis and therapy.
PMID: 29345434 [PubMed - as supplied by publisher]
Underlying mechanism of the photodynamic activity of hematoporphyrin‑induced apoptosis in U87 glioma cells.
Int J Mol Med. 2018 Jan 18;:
Authors: Yuan SX, Li JL, Xu XK, Chen W, Chen C, Kuang KQ, Wang FY, Wang K, Li FC
Photodynamic therapy (PDT) is a relatively novel type of tumor therapy method with low toxicity and limited side‑effects. The aim of the present study was to investigate the underlying mechanism and potential microRNAs (miRNAs) involved in the treatment of glioma by PDT with hematoporphyrin, a clinical photosensitizer. The photodynamic activity of hematoporphyrin on the cell viability and apoptosis of gliomas was investigated by MTT, and flow cytometry and fluorescence microscopy, respectively. Alterations in singlet oxygen and mitochondrial membrane potential were detected. The differentially expressed miRNAs and proteins were evaluated by miRNA gene chip and apoptosis‑associated protein chip, respectively. The results demonstrated that cell viability significantly decreased with hematoporphyrin concentration. PDT with hematoporphyrin significantly increased cell apoptosis at a later stage, induced the content of reactive oxygen species (ROS) and decreased the mitochondrial membrane potential, indicating that PDT with hematoporphyrin inhibited cell growth via induction of radical oxygen, decreased the mitochondrial membrane potential and induced apoptosis. The upregulated miRNAs, including hsa‑miR‑7641, hsa‑miR‑9500, hsa‑miR‑4459, hsa‑miR‑21‑5p, hsa‑miR‑663a and hsa‑miR‑205‑5p may be important in PDT‑induced cell apoptosis in glioma. Transporter 1, ATP binding cassette subfamily B member‑ and nuclear factor‑κB‑mediated apoptosis signaling pathways were the most significant pathways. Thus, the current study presents PDT as a potential therapeutic approach for the treatment of malignant glioma, and identified miRNAs for the molecular design and development of a third‑generation photosensitizer (PS).
PMID: 29344634 [PubMed - as supplied by publisher]
WST11 Vascular Targeted Photodynamic Therapy Effect Monitoring by Multispectral Optoacoustic Tomography (MSOT) in Mice.
Authors: Neuschmelting V, Kim K, Malekzadeh-Najafabadi J, Jebiwott S, Prakash J, Scherz A, Coleman JA, Kircher MF, Ntziachristos V
Objective: Monitoring emerging vascular-targeted photodynamic therapy (VTP) and understanding the time-dynamics of treatment effects remains challenging. We interrogated whether handheld multispectral optoacoustic tomography (MSOT) could noninvasively monitor the effect of VTP using WST11, a vascular-acting photosensitizer, on tumor tissues over time using a renal cell cancer mouse model. We also investigated whether MSOT illumination can induce VTP, to implement a single-modality theranostic approach. Materials and Methods: Eight BalB/c mice were subcutaneously implanted with murine renal adenocarcinoma cells (RENCA) on the flank. Three weeks later VTP was performed (10 min continuous illumination at 753 nm following intravenous infusion using WST11 or saline as control. Handheld MSOT images were collected prior to VTP administration and subsequently thereafter over the course of the first hour, at 24 and 48 h. Data collected were unmixed for blood oxygen saturation in tissue (SO2) based on the spectral signatures of deoxy- and oxygenated hemoglobin. Changes in oxygen saturation over time, relative to baseline, were examined by paired t-test for statistical significance (p < 0.05). In-vivo findings were corroborated by histological analyses of the tumor tissue. Results: MSOT is shown to prominently resolve changes in oxygen saturation in tumors within the first 20 min post WST11-VTP treatment. Within the first hour post-treatment, SO2 decreased by more than 60% over baseline (p < 0.05), whereas it remained unchanged (p > 0.1) in the sham-treated group. Moreover, unlike in the control group, SO2 in treated tumors further decreased over the course of 24 to 48 h post-treatment, concomitant with the propagation of profound central tumor necrosis present in histological analysis. We further show that pulsed MSOT illumination can activate WST11 as efficiently as the continuous wave irradiation employed for treatment. Conclusion: Handheld MSOT non-invasively monitored WST11-VTP effects based on the SO2 signal and detected blood saturation changes within the first 20 min post-treatment. MSOT may potentially serve as a means for both VTP induction and real-time VTP monitoring in a theranostic approach.
PMID: 29344301 [PubMed - in process]
Potent peptide-conjugated silicon phthalocyanines for tumor photodynamic therapy.
J Cancer. 2018;9(2):310-320
Authors: Liu Q, Pang M, Tan S, Wang J, Chen Q, Wang K, Wu W, Hong Z
Phthalocyanines (Pcs) are a group of promising photosensitizers for use in photodynamic therapy (PDT). However, their extremely low solubility and their strong tendency to aggregate in aqueous solution greatly restrict their application. Conjugation of Pc macrocycles with peptide ligands could be a very useful strategy to optimize the physical properties of Pcs not only by increasing their water solubility and reducing their aggregation but also by endowing the conjugates with a tumor-targeting capability. To develop highly potent photosensitizers for tumor PDT, we prepared new peptide-conjugated photosensitizers using silicon Pc (SiPc), which has much higher photodynamic activity than zinc Pcs, as the light activation moiety and the cRGDfK peptide (or simply cRGD) as the peptide moiety. A polyethylene glycol linker and an extra carboxylic acid group were also tested for introduction into the conjugates to optimize the conjugate structure. The conjugates' photophysical and photodynamic behaviors were then carefully evaluated and compared using in vitro and in vivo experiments. One of the prepared conjugates, RGD-(Linker)2-Glu-SiPc, showed excellent physical properties and photodynamic activity, with an EC50 (half maximal effective concentration) of 10-20 nM toward various cancer cells. This conjugate eradicated human glioblastoma U87-MG tumors in a xenograft murine tumor model after only one dose of photodynamic treatment, with no tumor regrowth during observation for up to 35 days. The conjugate RGD-(Linker)2-Glu-SiPc thus showed highly promising potential for use in tumor treatment.
PMID: 29344278 [PubMed]
Urothelial Tumors and Dual-Band Imaging: A New Concept in Confocal Laser Endomicroscopy.
J Endourol. 2017 May;31(5):538-544
Authors: Marien A, Rock A, Maadarani KE, Francois C, Gosset P, Mauroy B, Bonnal JL
OBJECTIVES: Confocal laser endomicroscopy (CLE) uses a low-energy laser light source to obtain microscopic histology images of bladder tissue exposed to a fluorescent dye. To evaluate the feasibility of using CLE with two fluorophores: fluorescein (FLUO) and hexylaminolevulinate (HAL) to determine histologic and cytologic bladder cancer criteria.
METHODS: Patients eligible for HAL-photodynamic diagnosis-assisted transurethral resection of bladder tumor were included. The procedures were performed with the patient under regional or general anesthesia (60-90 minutes) after bladder instillation of HAL (50 mL, 8 mmol/L; Hexvix®; Ipsen, France). Resected tissue was examined ex vivo using CLE either with Cellvizio® system (CVI) single laser (488 nm) or with Cellvizio Dual system (CVII) double laser (488, 660 nm).
RESULTS: Twenty-one patients were included, 12 examined by CVI and 9 by CVII. Sample examination on CVI after HAL-CLE-only histologic analysis was not possible because HAL is mostly cytoplasmic and gives poor details on cellular architecture. On the contrary, FLUO-CLE gives good extracellular architecture and not clear information of nucleocytoplasmic abnormality. Samples on CVII for seven out of nine patients clearly showed cytoplasm of suspect cells and nuclei. In real time, fluorescence observed on bandwidth (673-800 nm) with HAL and FLUO was associated with the presence of cancer, with a sensibility and specificity of 80% and 100%, respectively.
CONCLUSIONS: Real-time cytodetection was feasible using two fluorophores (FLUO and HAL) and the new system of CVII. This technology was useful to observe cytoplasm, nuclei, and nucleocytoplasmic abnormality, but an improved system is necessary (to overcome the overlapping of fluorescence) to increase the specificity.
PMID: 28326794 [PubMed - indexed for MEDLINE]