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Review: Organic nanoparticle based active targeting for photodynamic therapy treatment of breast cancer cells.

ABSTRACT: Targeted Photodynamic therapy (TPDT) is a non-invasive and site-specific treatment modality, which has been utilized to eradicate cancer tumour cells with photoactivated chemicals or photosensitizers (PSs), in the presence of laser light irradiation and molecular tissue oxygen. Breast cancer is the commonest cancer among women worldwide and is currently treated using conventional methods such as chemotherapy, radiotherapy and surgery. Despite the recent advancements made in PDT, poor water solubility and non-specificity of PSs, often affect the overall effectivity of this unconventional cancer treatment. With respect to conventional PS obstacles, great strides have been made towards the application of targeted nanoparticles in PDT to resolve these limitations. Therefore, this review provides an overview of scientific peer reviewed published studies in relation to functionalized organic nanoparticles (NPs) for effective TPDT treatment of breast cancer over the last 10 years (2009 to 2019). The main aim of this review is to highlight the importance of organic NP active based PDT targeted drug delivery systems, to improve the overall biodistribution of PSs in breast cancer tumour's.

SUBMITTER: Montaseri H

PROVIDER: S-EPMC7275783 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Review: Organic nanoparticle based active targeting for photodynamic therapy treatment of breast cancer cells.

Montaseri Hanieh H Kruger Cherie Ann CA Abrahamse Heidi H

Oncotarget 20200602 22

Targeted Photodynamic therapy (TPDT) is a non-invasive and site-specific treatment modality, which has been utilized to eradicate cancer tumour cells with photoactivated chemicals or photosensitizers (PSs), in the presence of laser light irradiation and molecular tissue oxygen. Breast cancer is the commonest cancer among women worldwide and is currently treated using conventional methods such as chemotherapy, radiotherapy and surgery. Despite the recent advancements made in PDT, poor water solub ...[more]

PMID: 32547709

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Project description:This review article is based on specifically targeted nanoparticles that have been used in the treatment of melanoma. According to the Skin Cancer Foundation, within 2017 an estimated 9730 people will die due to invasive melanoma. Conventional treatments for nonmalignant melanoma include surgery, chemotherapy, and radiation. For the treatment of metastatic melanoma, 3 therapeutic agents have been approved by the Food and Drug Administration: dacarbazine, recombinant interferon ?-2b, and high-dose interleukin 2. Photodynamic therapy is an alternative therapy that activates a photosensitizer at a specific wavelength forming reactive oxygen species which in turn induces cell death; it is noninvasive with far less side effects when compared to conventional treatments. Nanoparticles are generally conjugated to photosynthetic drugs, since they are biocompatible, stabile, and durable, as well as have a high loading capacity, which improve either passive or active photosensitizer drug delivery to targeted cells. Therefore, various photosynthetic drugs and nanoparticle drug delivery systems specifically targeted for melanoma were analyzed in this review article in relation to either their passive or their active cellular uptake mechanisms in order to deduce the efficacy of photodynamic therapy treatment for metastatic melanoma which currently remains ongoing. The overall findings from this review concluded that no current photodynamic therapy studies have been performed in relation to active nanoparticle platform photosensitizer drug carrier systems for the treatment of metastatic melanoma, and so this type of research requires further investigation into developing a more efficient active nano-photosensitizer carrier smart drug that can be conjugated to specific cell surface receptors and combinative monoclonal antibodies so that a further enhanced and more efficient form of targeted photodynamic therapy for the treatment of metastatic melanoma can be established.

Project description:Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum (ER)-resident chaperone and a major regulator of the unfolded protein response (UPR). Accumulating evidence indicate that GRP78 is overexpressed in many cancer cell lines, and contributes to the invasion and metastasis in many human tumors. Besides, GRP78 upregulation is detected in response to different ER stress-inducing anticancer therapies, including photodynamic therapy (PDT). This study demonstrates that GRP78 mRNA and protein levels are elevated in response to PDT in various cancer cell lines. Stable overexpression of GRP78 confers resistance to PDT substantiating its cytoprotective role. Moreover, GRP78-targeting subtilase cytotoxin catalytic subunit fused with epidermal growth factor (EGF-SubA) sensitizes various cancer cells to Photofrin-mediated PDT. The combination treatment is cytotoxic to apoptosis-competent SW-900 lung cancer cells, as well as to Bax-deficient and apoptosis-resistant DU-145 prostate cancer cells. In these cells, PDT and EGF-SubA cytotoxin induce protein kinase R-like ER kinase and inositol-requiring enzyme 1 branches of UPR and also increase the level of C/EBP (CCAAT/enhancer-binding protein) homologous protein, an ER stress-associated apoptosis-promoting transcription factor. Although some apoptotic events such as disruption of mitochondrial membrane and caspase activation are detected after PDT, there is no phosphatidylserine plasma membrane externalization or DNA fragmentation, suggesting that in DU-145 cells the late apoptotic events are missing. Moreover, in SW-900 cells, EGF-SubA cytotoxin potentiates PDT-mediated cell death but attenuates PDT-induced apoptosis. In addition, the cell death cannot be reversed by caspase inhibitor z-VAD, confirming that apoptosis is not a major cell death mode triggered by the combination therapy. Moreover, no typical features of necrotic or autophagic cell death are recognized. Instead, an extensive cellular vacuolation of ER origin is observed. Altogether, these findings indicate that PDT and GRP78-targeting cytotoxin treatment can efficiently kill cancer cells independent on their apoptotic competence and triggers an atypical, non-apoptotic cell death.

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Review: Organic nanoparticle based active targeting for photodynamic therapy treatment of breast cancer cells.

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Review: Organic nanoparticle based active targeting for photodynamic therapy treatment of breast cancer cells.

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