Photodynamic therapy activity of new porphyrin-xylan-coated silica nanoparticles in a human colorectal cancer in vivo model

2019 ◽  
Author(s):  
Ludovic Bretin ◽  
David Yannick Leger ◽  
Aline Pinon ◽  
Soukaina Bouramtane ◽  
Frédérique Bregier ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Photodynamic Therapy ◽  
Silica Nanoparticles ◽  
In Vivo Model ◽  
Human Colorectal Cancer

scholarly journals Photodynamic Therapy Activity of New Porphyrin-Xylan-Coated Silica Nanoparticles in Human Colorectal Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1474 ◽  
Author(s):  
Ludovic Bretin ◽  
Aline Pinon ◽  
Soukaina Bouramtane ◽  
Catherine Ouk ◽  
Laurence Richard ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Photodynamic Therapy ◽  
Silica Nanoparticles ◽  
Solid Tumors ◽  
Tumor Targeting ◽  
Added Value ◽  
Cell Uptake ◽  
Human Colorectal Cancer ◽  
Anticancer Efficacy

Photodynamic therapy (PDT) using porphyrins has been approved for treatment of several solid tumors due to the generation of cytotoxic reactive oxygen species (ROS). However, low physiological solubility and lack of selectivity towards tumor sites are the main limitations of their clinical use. Nanoparticles are able to spontaneously accumulate in solid tumors through an enhanced permeability and retention (EPR) effect due to leaky vasculature, poor lymphatic drainage, and increased vessel permeability. Herein, we proved the added value of nanoparticle vectorization on anticancer efficacy and tumor-targeting by 5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (TPPOH). Using 80 nm silica nanoparticles (SNPs) coated with xylan-TPPOH conjugate (TPPOH-X), we first showed very significant phototoxic effects of TPPOH-X SNPs mediated by post-PDT ROS generation and stronger cell uptake in human colorectal cancer cell lines compared to free TPPOH. Additionally, we demonstrated apoptotic cell death induced by TPPOH-X SNPs-PDT and the interest of autophagy inhibition to increase anticancer efficacy. Finally, we highlighted in vivo, without toxicity, elevated anticancer efficacy of TPPOH-X SNPs through improvement of tumor-targeting compared to a free TPPOH protocol. Our work demonstrated for the first time the strong anticancer efficacy of TPPOH in vitro and in vivo and the merit of SNPs vectorization.

scholarly journals Photodynamic therapy induces autophagy-mediated cell death in human colorectal cancer cells via activation of the ROS/JNK signaling pathway

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Changfeng Song ◽  
Wen Xu ◽  
Hongkun Wu ◽  
Xiaotong Wang ◽  
Qianyi Gong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Photodynamic Therapy ◽  
Signaling Pathway ◽  
Tumor Promoter ◽  
Human Colorectal Cancer ◽  
In Vivo Models ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

Abstract Evidence has shown that m-THPC and verteporfin (VP) are promising sensitizers in photodynamic therapy (PDT). In addition, autophagy can act as a tumor suppressor or a tumor promoter depending on the photosensitizer (PS) and the cancer cell type. However, the role of autophagy in m-THPC- and VP-mediated PDT in in vitro and in vivo models of human colorectal cancer (CRC) has not been reported. In this study, m-THPC-PDT or VP-PDT exhibited significant phototoxicity, inhibited proliferation, and induced the generation of large amounts of reactive oxygen species (ROS) in CRC cells. From immunoblotting, fluorescence image analysis, and transmission electron microscopy, we found extensive autophagic activation induced by ROS in cells. In addition, m-THPC-PDT or VP-PDT treatment significantly induced apoptosis in CRC cells. Interestingly, the inhibition of m-THPC-PDT-induced autophagy by knockdown of ATG5 or ATG7 substantially inhibited the apoptosis of CRC cells. Moreover, m-THPC-PDT treatment inhibited tumorigenesis of subcutaneous HCT116 xenografts. Meanwhile, antioxidant treatment markedly inhibited autophagy and apoptosis induced by PDT in CRC cells by inactivating JNK signaling. In conclusion, inhibition of autophagy can remarkably alleviate PDT-mediated anticancer efficiency in CRC cells via inactivation of the ROS/JNK signaling pathway. Our study provides evidence for the therapeutic application of m-THPC and VP in CRC.

Beyond radiation therapy: photodynamic therapy maintains structural integrity of irradiated healthy and metastatically involved vertebrae in a pre-clinical in vivo model

2012 ◽  
Vol 135 (2) ◽  
pp. 391-401 ◽  
Author(s):  
Victor C. K. Lo ◽  
Margarete K. Akens ◽  
Sara Moore ◽  
Albert J. M. Yee ◽  
Brian C. Wilson ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Photodynamic Therapy ◽  
Structural Integrity ◽  
In Vivo Model

scholarly journals Development of Preclinical Models to Understand and Treat Colorectal Cancer

2018 ◽  
Vol 31 (03) ◽  
pp. 199-204 ◽  
Author(s):  
Judith Sebolt-Leopold
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Tumors ◽  
Human Colorectal Cancer ◽  
Preclinical Models ◽  
In Vivo Models ◽  
Molecular Determinants ◽  
Experimental Therapies ◽  
Molecular Aberrations

AbstractThe establishment and validation of preclinical models that faithfully recapitulate the pathogenesis and treatment response of human colorectal cancer (CRC) is critical to expedient therapeutic advances in the clinical management of this disease. Integral to the application of precision medicine for patients diagnosed with metastatic CRC is the need to understand the molecular determinants of response for a given therapy. Preclinical models of CRC have proven invaluable in answering many of our basic questions relating to the molecular aberrations that drive colorectal tumor progression. This review will address the comparative merits and limitations of the broad spectrum of in vitro and in vivo models available for study of colorectal tumors and their response to experimental therapies.

Application of Genetically-Engineered Anti-CEA Antibodies for Potential Immunotherapy of Colorectal Cancer

1992 ◽  
Vol 7 (3) ◽  
pp. 203-209 ◽  
Author(s):  
N. Hardman ◽  
B. Murray ◽  
M. Zwickl ◽  
F. Kolbinger ◽  
G. Pluschke
Keyword(s):  
Colorectal Cancer ◽  
Clinical Utility ◽  
Malignant Disease ◽  
Genetic Manipulation ◽  
Repeated Administration ◽  
Genetically Engineered ◽  
Cytotoxic Agents ◽  
Human Colorectal Cancer ◽  
In Vivo Diagnosis

Hitherto anti-CEA monoclonal antibodies (MAbs), normally of mouse origin, have been used primarily for clinical diagnosis of colorectal cancer, either as a tumor marker in serum to monitor tumor recurrence, or latterly as a means to localize in vivo CEA-bearing tumors and metastases in patients. In vivo diagnosis using mouse anti-CEA MAbs has so far had limited clinical utility because the antibodies elicit a strong anti-mouse immunoglobulin immune response on repeated administration in man. This problem has been addressed by the development of various strategies for “humanization” of mouse anti-CEA MAbs by genetic manipulation of immunoglobulin genes. Such humanized, engineered antibodies markedly attenuate the antigenic response directed against the MAb, such that safe, repeated administration to patients has become feasible. Such humanized anti-CEA antibodies can thus be radioactively-labelled and applied for in vivo monitoring and detection of recurrent malignant disease, or used for therapeutic strategies which similarly take advantage of the ability of the antibodies to target cytotoxic agents selectively to tumor cells. The application of these novel procedures for manipulating MAb structure presents entirely new opportunities for diagnosis and treatment of human colorectal cancer.

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