Non-Oncologic Applications of Nanomedicine-Based Phototherapy.

Phototherapy is widely applied to various human diseases. Nanomedicine-based phototherapy can be classified into photodynamic therapy (PDT) and photothermal therapy (PTT). Activated photosensitizer kills the target cells by generating radicals or reactive oxygen species in PDT while generating heat in PTT. Both PDT and PTT have been employed for treating various diseases, from preclinical to randomized controlled clinical trials. However, there are still hurdles to overcome before entering clinical practice. This review provides an overview of nanomedicine-based phototherapy, especially in non-oncologic diseases. Multiple clinical trials were undertaken to prove the therapeutic efficacy of PDT in dermatologic, ophthalmologic, cardiovascular, and dental diseases. Preclinical studies showed the feasibility of PDT in neurologic, gastrointestinal, respiratory, and musculoskeletal diseases. A few clinical studies of PTT were tried in atherosclerosis and dry eye syndrome. Although most studies have shown promising results, there have been limitations in specificity, targeting efficiency, and tissue penetration using phototherapy. Recently, nanomaterials have shown promising results to overcome these limitations. With advanced technology, nanomedicine-based phototherapy holds great potential for broader clinical practice.

Multicolor fluorescence imaging using a single RGB-IR CMOS sensor for cancer detection with smURFP-labeled probiotics.

A multicolor fluorescence imaging device was recently developed for image-guided surgery. However, conventional systems are typically bulky and function with two cameras. To overcome these issues, we developed an economical home-built fluorescence imaging device based on a single RGB-IR sensor that can acquire both color and fluorescence images simultaneously. The technical feasibility of RGB-IR imaging was verified ex vivo in chicken breast tissue using fluorescein isothiocyanate (FITC), cyanine 5 (Cy5), and indocyanine green (ICG) as fluorescent agents. The minimum sensitivities for FITC, Cy5, and ICG were 0.200 µM, 0.130 µM, and 0.065 µM, respectively. In addition, we validated the fluorescence imaging of this device in vitro during a minimally invasive procedure using smURFP-labeled probiotics, which emit a spectrum similar to that of Cy5. Our preliminary study of the ex vivo tissue suggests that Cy5 and ICG are good candidates for deep tissue imaging. In addition, the tumor-specific amplification process was visualized using cancer cells incubated with probiotics that had been labeled with a fluorescent protein. Our approach indicates the potential for in vivo screening of tumors in rodent tumor models.

Erratum: Multicolor fluorescence imaging using a single RGB-IR CMOS sensor for cancer detection with smURFP-labeled probiotics: publisher's note.

[This corrects the article on p. 2951 in vol. 11, PMID: 32637234.].

Multi-Spectral Fluorescence Imaging of Colon Dysplasia InVivo Using a Multi-Spectral Endoscopy System.

BACKGROUND AND STUDY AIM: To develop a molecular imaging endoscopic system that eliminates tissue autofluorescence and distinguishes multiple fluorescent markers specifically on the cancerous lesions. METHODS: Newly developed multi-spectral fluorescence endoscope device has the potential to eliminate signal interference due to autofluorescence and multiplex fluorophores in fluorescent probes. The multiplexing capability of the multi-spectral endoscope device was demonstrated in the phantom studies and multi-spectral imaging with endoscopy and macroscopy was performed to analyze fluorescence signals after administration of fluorescent probe that targets cancer in the colon. Because of the limitations in the clinical application using rigid-type small animal endoscope, we developed a flexible channel insert-type fluorescence endoscope, which was validated on the colonoscopy of dummy and porcine model. RESULTS: We measured multiple fluorescent signals simultaneously, and the fluorescence spectra were unmixed to separate the fluorescent signals of each probe, in which multiple fluorescent probes clearly revealed spectral deconvolution at the specific targeting area in the mouse colon. The positive area of fluorescence signal for each probe over the whole polyp was segmented with analyzing software, and showed distinctive patterns and significantly distinguishable values: 0.46 ±â€¯0.04, 0.39 ±â€¯0.08 and 0.73 ±â€¯0.12 for HMRG, CET-553 and TRA-675 probes, respectively. The spectral unmixing was finally demonstrated in the dummy and porcine model, corroborating the targeted multi-spectral fluorescence imaging of colon dysplasia. CONCLUSION: The multi-spectral endoscopy system may allow endoscopists to clearly identify cancerous lesion that has different patterns of various target expression using multiple fluorescent probes.

Endoscopic non-ablative fractional laser therapy in an orthotopic colon tumour model.

Colorectal cancer is one of the leading causes of cancer-related deaths. Although several therapeutic management strategies are available at the early colon cancer stages, such as endoscopic mucosal or submucosal dissection, associated complications often include bleeding or bowel perforations. As an alternative approach, we investigated endoscopic non-ablative fractional laser (eNAFL) irradiation as a minimally invasive therapeutic modality for the treatment of early-stage colorectal cancer. By implanting SL4-DsRed colon cancer cells into the colons of the C57BL/6 mice, we developed an orthotopic colon tumour mouse model and demonstrated the early-stage tumour growth delay following the eNAFL irradiation. Additionally, we evaluated the temperature changes in the eNAFL-irradiated area using numerical simulations, and induced inflammation using histological analysis. Our results indicate a minimal thermal damage confined to the irradiated spot, sparing the adjacent tissue and alteration in the tumour microenvironment. eNAFL irradiation may be clinically useful as a minimally invasive therapeutic intervention at the early stage of tumourigenesis. In future, an optimal eNAFL therapeutic dose should be determined, in order to increase the efficacy of this approach.

Active thermodynamic contrast imaging for label-free tumor detection in a murine xenograft tumor model.

Passive thermal imaging provides a limited differentiation between a tumor and neighboring tissue based on the temperature difference. We propose active thermodynamic contrast imaging (ATCI) with convection thermal modulators to provide more physiologically relevant parameters with high contrast such as the rate of temperature change, and thermal recovery time for tumor detection with a murine xenograft tumor model. With early stage tumors, we found the average rate of temperature change was higher in the tumor (0.22 ± 0.06 [Formula: see text]/sec) than that of neighboring tissue (0.13 ± 0.01 [Formula: see text]/sec) with heating modulation. With established tumors (volume > 100 mm3), this tendency was greater. On the other hand, the thermal recovery time was shorter in tumor tissue (τ = 7.30 ± 0.59 sec) than that of neighboring tissue (τ = 11.91 ± 2.22 sec). We also found distinct thermal contrast with cooling modulation. These data suggest ATCI is a potential tumor detection modality for clinical application with its inherently label-free and physiology-based approach. Furthermore, this strategy may find applications in endoscopic tumor detection in the future.

A High-Affinity Repebody for Molecular Imaging of EGFR-Expressing Malignant Tumors.

The accurate detection of disease-related biomarkers is crucial for the early diagnosis and management of disease in personalized medicine. Here, we present a molecular imaging of human epidermal growth factor receptor (EGFR)-expressing malignant tumors using an EGFR-specific repebody composed of leucine-rich repeat (LRR) modules. The repebody was labeled with either a fluorescent dye or radioisotope, and used for imaging of EGFR-expressing malignant tumors using an optical method and positron emission tomography. Our approach enabled visualization of the status of EGFR expression, allowing quantitative evaluation in whole tumors, which correlated well with the EGFR expression levels in mouse or patients-derived colon cancers. The present approach can be effectively used for the accurate detection of EGFR-expressing cancers, assisting in the development of a tool for detecting other disease biomarkers.

Intravital imaging of mouse colonic adenoma using MMP-based molecular probes with multi-channel fluorescence endoscopy.

Intravital imaging has provided molecular, cellular and anatomical insight into the study of tumor. Early detection and treatment of gastrointestinal (GI) diseases can be enhanced with specific molecular markers and endoscopic imaging modalities. We present a wide-field multi-channel fluorescence endoscope to screen GI tract for colon cancer using multiple molecular probes targeting matrix metalloproteinases (MMP) conjugated with quantum dots (QD) in AOM/DSS mouse model. MMP9 and MMP14 antibody (Ab)-QD conjugates demonstrate specific binding to colonic adenoma. The average target-to-background (T/B) ratios are 2.10 ± 0.28 and 1.78 ± 0.18 for MMP14 Ab-QD and MMP9 Ab-QD, respectively. The overlap between the two molecular probes is 67.7 ± 8.4%. The presence of false negative indicates that even more number of targeting could increase the sensitivity of overall detection given heterogeneous molecular expression in tumors. Our approach indicates potential for the screening of small or flat lesions that are precancerous.