scholarly journals NIR-II emissive AIEgen photosensitizers enable ultrasensitive imaging-guided surgery and phototherapy to fully inhibit orthotopic hepatic tumors

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ruizhen Jia ◽  
Han Xu ◽  
Chenlu Wang ◽  
Lichao Su ◽  
Jinpeng Jing ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Near Infrared ◽  
Liver Tumors ◽  
Early Stage ◽  
Oxygen Species ◽  
Hepatic Tumors ◽  
Primary Liver Tumors ◽  
Guided Surgery

AbstractAccurate diagnosis and effective treatment of primary liver tumors are of great significance, and optical imaging has been widely employed in clinical imaging-guided surgery for liver tumors. The second near-infrared window (NIR-II) emissive AIEgen photosensitizers have attracted a lot of attention with higher-resolution bioimaging and deeper penetration. NIR-II aggregation-induced emission-based luminogen (AIEgen) photosensitizers have better phototherapeutic effects and accuracy of the image-guided surgery/phototherapy. Herein, an NIR-II AIEgen phototheranostic dot was proposed for NIR-II imaging-guided resection surgery and phototherapy for orthotopic hepatic tumors. Compared with indocyanine green (ICG), the AIEgen dots showed bright and sharp NIR-II emission at 1250 nm, which extended to 1600 nm with high photostability. Moreover, the AIEgen dots efficiently generated reactive oxygen species (ROS) for photodynamic therapy. Investigations of orthotopic liver tumors in vitro and in vivo demonstrated that AIEgen dots could be employed both for imaging-guided tumor surgery of early-stage tumors and for ‘downstaging’ intention to reduce the size. Moreover, the therapeutic strategy induced complete inhibition of orthotopic tumors without recurrence and with few side effects. Graphical Abstract

scholarly journals In Vivo Models for Cholangiocarcinoma—What Can We Learn for Human Disease?

2020 ◽  
Vol 21 (14) ◽  
pp. 4993 ◽  
Author(s):  
Raphael Mohr ◽  
Burcin Özdirik ◽  
Jana Knorr ◽  
Alexander Wree ◽  
Münevver Demir ◽  
...  
Keyword(s):  
Animal Models ◽  
Human Disease ◽  
Liver Tumors ◽  
Tumor Biology ◽  
Genetic Alterations ◽  
In Vivo Models ◽  
Primary Liver Tumors ◽  
Stromal Microenvironment

Cholangiocarcinoma (CCA) comprises a heterogeneous group of primary liver tumors. They emerge from different hepatic (progenitor) cell populations, typically via sporadic mutations. Chronic biliary inflammation, as seen in primary sclerosing cholangitis (PSC), may trigger CCA development. Although several efforts were made in the last decade to better understand the complex processes of biliary carcinogenesis, it was only recently that new therapeutic advances have been achieved. Animal models are a crucial bridge between in vitro findings on molecular or genetic alterations, pathophysiological understanding, and new therapeutic strategies for the clinic. Nevertheless, it is inherently difficult to recapitulate simultaneously the stromal microenvironment (e.g., immune-competent cells, cholestasis, inflammation, PSC-like changes, fibrosis) and the tumor biology (e.g., mutational burden, local growth, and metastatic spread) in an animal model, so that it would reflect the full clinical reality of CCA. In this review, we highlight available data on animal models for CCA. We discuss if and how these models reflect human disease and whether they can serve as a tool for understanding the pathogenesis, or for predicting a treatment response in patients. In addition, open issues for future developments will be discussed.

scholarly journals Injectable and Temperature-Sensitive Titanium Carbide-Loaded Hydrogel System for Photothermal Therapy of Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Jun Yao ◽  
Chuanda Zhu ◽  
Tianjiao Peng ◽  
Qiang Ma ◽  
Shegan Gao
Keyword(s):  
Titanium Carbide ◽  
Cancer Treatment ◽  
Photothermal Therapy ◽  
Therapeutic Strategy ◽  
Near Infrared ◽  
Pluronic F127 ◽  
Temperature Sensitive ◽  
Hydrogel System

Recently, organic–inorganic hybrid materials have gained much attention as effective photothermal agents for cancer treatment. In this study, Pluronic F127 hydrogel-coated titanium carbide (Ti3C2) nanoparticles were utilized as an injectable photothermal agent. The advantages of these nanoparticles are their green synthesis and excellent photothermal efficiency. In this system, lasers were mainly used to irradiate Ti3C2 nanoparticles to produce a constant high temperature, which damaged cancer cells. The nanoparticles were found to be stable during storage at low temperatures for at least 2 weeks. The Ti3C2 nanoparticles exhibited a shuttle-shaped structure, and the hydrogels presented a loosely meshed structure. In addition, Ti3C2 nanoparticles did not affect the reversible temperature sensitivity of the gel, and the hydrogel did not affect the photothermal properties of Ti3C2 nanoparticles. The in vitro and in vivo results show that this hydrogel system can effectively inhibit tumor growth upon exposure to near-infrared irradiation with excellent biocompatibility and biosafety. The photothermal agent-embedded hydrogel is a promising photothermal therapeutic strategy for cancer treatment by enhancing the retention in vivo and elevating the local temperature in tumors.

scholarly journals Pharmacokinetic and Biodistribution Assessment of a Near Infrared-Labeled PSMA-Specific Small Molecule in Tumor-Bearing Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Joy L. Kovar ◽  
Lael L. Cheung ◽  
Melanie A. Simpson ◽  
D. Michael Olive
Keyword(s):  
Small Molecule ◽  
Near Infrared ◽  
Image Guided Surgery ◽  
Tumor Delineation ◽  
Guided Surgery ◽  
Image Guided ◽  
Tumor Bearing ◽  
Tissue Contrast

Prostate cancer is the most frequently diagnosed cancer in men and often requires surgery. Use of near infrared (NIR) technologies to perform image-guided surgery may improve accurate delineation of tumor margins. To facilitate preclinical testing of such outcomes, here we developed and characterized a PSMA-targeted small molecule, YC-27. IRDye 800CW was conjugated to YC-27 or an anti-PSMA antibody used for reference. Human 22Rv1, PC3M-LN4, and/or LNCaP prostate tumor cells were exposed to the labeled compounds.In vivotargeting and clearance properties were determined in tumor-bearing mice. Organs and tumors were excised and imaged to assess probe localization. YC-27 exhibited a dose dependent increase in signal upon binding. Binding specificity and internalization were visualized by microscopy.In vitroandin vivoblocking studies confirmed YC-27 specificity.In vivo, YC-27 showed good tumor delineation and tissue contrast at doses as low as 0.25 nmole. YC-27 was cleared via the kidneys but bound the proximal tubules of the renal cortex and epididymis. Since PSMA is also broadly expressed on the neovasculature of most tumors, we expect YC-27 will have clinical utility for image-guided surgery and tumor resections.

scholarly journals Sequential Drug Delivery By Injectable Macroporous Hydrogels For Combined Photodynamic-Chemotherapy

2021 ◽  
Author(s):  
Yuanyuan Zhong ◽  
Li Zhang ◽  
Shian Sun ◽  
Zhenghao Zhou ◽  
Yunsu Ma ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Near Infrared ◽  
Early Stage ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Sequential Release ◽  
Therapy Effect ◽  
Hollow Mesoporous Silica

Abstract With hollow mesoporous silica (hMSN) and injectable macroporous hydrogel (Gel) used as the internal and external drug-loading material respectively, a sequential drug delivery system DOX-CA4P@Gel was constructed, in which combretastatin A4 phosphate (CA4P) and doxorubicin (DOX) were both loaded. The anti-angiogenic drug, CA4P was initially released due to the degradation of Gel, followed by the anti-cell proliferative drug, DOX, released from hMSN in tumor microenvironment. Results showed that CA4P was mainly released at the early stage. At 48 h, CA4P release reached 71.08%, while DOX was only 14.39%. At 144 h, CA4P was 78.20%, while DOX release significantly increased to 61.60%, showing an obvious sequential release behavior. Photodynamic properties of porphyrin endow hydrogel (φΔ(Gel)=0.91) with enhanced tumor therapy effect. In vitro and in vivo experiments showed that dual drugs treated groups have better tumor inhibition than solo drug under near infrared laser irradiation, indicating the effectivity of combined photodynamic-chemotherapy.

scholarly journals Fluorescence-Guided Surgery for Hepatoblastoma with Indocyanine Green

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1215 ◽  
Author(s):  
Yohei Yamada ◽  
Michinobu Ohno ◽  
Akihiro Fujino ◽  
Yutaka Kanamori ◽  
Rie Irie ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Patient Survival ◽  
Liver Tumors ◽  
Distant Metastases ◽  
Complete Resection ◽  
Hepatic Tumors ◽  
Primary Liver Tumors ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Subsequent Patient

Fluorescence-guided surgery with indocyanine green (ICG) for malignant hepatic tumors has been gaining more attention with technical advancements. Since hepatoblastomas (HBs) possess similar features to hepatocellular carcinoma, fluorescence-guided surgery can be used for HBs, as aggressive surgical resection, even for distant metastases of HBs, often contributes positively to R0 (complete) resection and subsequent patient survival. Despite a few caveats, fluorescence-guided surgery allows for the more sensitive identification of lesions that may go undetected by conventional imaging or be invisible macroscopically. This leads to precise resection of distant metastatic tumors as well as primary liver tumors.

scholarly journals HuR Protein in Hepatocellular Carcinoma: Implications in Development, Prognosis and Treatment

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 119
Author(s):  
Vasiliki Papatheofani ◽  
Georgia Levidou ◽  
Panagiotis Sarantis ◽  
Evangelos Koustas ◽  
Michalis V. Karamouzis ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Tumors ◽  
Normal Liver ◽  
Primary Liver Tumors ◽  
The Stability ◽  
Hu Antigen R ◽  
Post Transcriptional Regulation

Hu-antigen R (HuR) is a post-transcriptional regulator that belongs to the embryonic lethal abnormal vision Drosophila-like family (ELAV). HuR regulates the stability, translation, subcellular localization, and degradation of several target mRNAs, which are implicated in carcinogenesis and could affect therapeutic options. HuR protein is consistently highly expressed in hepatocellular carcinoma (HCC) compared to the adjacent normal liver tissue and is involved in the post-transcriptional regulation of various genes implicated in liver malignant transformation. Additionally, HuR protein seems to be a putative prognosticator in HCC, predicting worse survival. This review summarizes the recent evidence regarding the role of HuR in primary liver tumors, as presented in clinical studies, in vitro experiments and in vivo animal models. In conclusion, our review supports the consistent role of HuR protein in the development, prognosis, and treatment of HCC. Additional studies are expected to expand current information and exploit its putative employment as a future candidate for more personalized treatment in these tumors.

scholarly journals Zinc Sulfide-Based Hybrid Exosome-Coated Nanoplatform for Targeted Treatment of Glioblastoma in an Orthotopic Mouse Glioblastoma Model

2020 ◽  
Author(s):  
Jingxin Mo
Keyword(s):  
Zinc Sulfide ◽  
Therapeutic Strategy ◽  
Autophagic Flux ◽  
Oxygen Species ◽  
Glioblastoma Cells ◽  
Zns Nanoparticles ◽  
Redox Responsive ◽  
Targeting Ability

Core-hybrid shell hydroxychloroquine (HCQ) loaded zinc sulfide (ZnS) nanoparticles were synthesized, characterized and evaluated for the treatment of glioblastoma cells in vitro and in vivo. These particles, denoted as HCQ@ZnS@exo@iRGD, consist of hollow ZnS nanoparticles loading with the autophagic inhibitor of hydroxychloroquine and covered by a hybrid shell containing exosomes (exo) and phosphatidylserine derived pH- and redox-responsive pegylated iRGD peptide, a gliomablastoma-homing and penetrating peptide. The hybrid exosomes enable HCQ@ZnS with good permeability across the blood-brain barrier and targeting ability to glioblastoma cells in orthotopic mouse glioblastoma model. ZnS acts as a photosensitizer for reactive oxygen species (ROS) production to inflict damage to organelles within glioblastoma cells. Hydroxychloroquine inhibits autophagic flux, which can subsequently lead to the accumulation of impaired organelles caused by the ROS. As a result, substantial selective damage to glioblastoma cells was realized owing to the hybrid exosomes guiding the anti-tumour effects of hydroxychloroquine and ZnS under light irradiation. The results provide evidence for the utility of HCQ@ZnS@exo@iRGD as a therapeutic strategy for glioblastoma.

scholarly journals Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Solmaz AghaAmiri ◽  
Jo Simien ◽  
Alastair M. Thompson ◽  
Julie Voss ◽  
Sukhen C. Ghosh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Near Infrared ◽  
Residual Disease ◽  
Ex Vivo ◽  
Guided Surgery ◽  
Nirf Imaging ◽  
Fluorescence Guided Surgery ◽  
Imaging Results

Background. Although therapeutic advances have led to enhanced survival in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, detection of residual disease remains challenging. Here, we examine two approved anti-HER2 monoclonal antibodies (mAbs), trastuzumab and pertuzumab, as potential candidates for the development of immunoconjugates for fluorescence-guided surgery (FGS). Methods. mAbs were conjugated to the near-infrared fluorescent (NIRF) dye, IRDye800, and for quantitative in vitro assessment, to the radiometal chelator, desferrioxamine, to enable dual labeling with 89Zr. In vitro binding was evaluated in HER2-overexpressing (BT474, SKBR3) and HER2-negative (MCF7) cell lines. BT474 and MCF7 xenografts were used for in vivo and ex vivo fluorescence imaging. Results. In vitro findings demonstrated HER2-mediated binding for both fluorescent immunoconjugates and were in agreement with radioligand assays using dual-labeled immunoconjugates. In vivo and ex vivo studies showed preferential accumulation of the fluorescently-labeled mAbs in tumors and similar tumor-to-background ratios. In vivo HER2 specificity was confirmed by immunohistochemical staining of resected tumors and normal tissues. Conclusions. We showed for the first time that fluorescent trastuzumab and pertuzumab immunoconjugates have similar NIRF imaging performance and demonstrated the possibility of performing HER2-targeted FGS with agents that possess distinct epitope specificity.

scholarly journals Role of interleukins in the pathogenesis of pulmonary fibrosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yi Xin She ◽  
Qing Yang Yu ◽  
Xiao Xiao Tang
Keyword(s):  
Pulmonary Fibrosis ◽  
Therapeutic Strategy ◽  
Future Directions ◽  
Regulation Mechanisms ◽  
Underlying Mechanisms ◽  
Multiple Cells ◽  
The Relationship

AbstractInterleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.

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