Review: Organic nanoparticle based active targeting for photodynamic therapy treatment of breast cancer cells.
Ontology highlight
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.
Project description:DNA-mediated assembly of core-satellite structures composed of Zr(IV)-based porphyrinic metal-organic framework (MOF) and NaYF4 ,Yb,Er upconverting nanoparticles (UCNPs) for photodynamic therapy (PDT) is reported. MOF NPs generate singlet oxygen (1 O2 ) upon photoirradiation with visible light without the need for additional small molecule, diffusional photosensitizers such as porphyrins. Using DNA as a templating agent, well-defined MOF-UCNP clusters are produced where UCNPs are spatially organized around a centrally located MOF NP. Under NIR irradiation, visible light emitted from the UCNPs is absorbed by the core MOF NP to produce 1 O2 at significantly greater amounts than what can be produced from simply mixing UCNPs and MOF NPs. The MOF-UCNP core-satellite superstructures also induce strong cell cytotoxicity against cancer cells, which are further enhanced by attaching epidermal growth factor receptor targeting affibodies to the PDT clusters, highlighting their promise as theranostic photodynamic agents.
Project description:Active-targeted nanoplatforms could specifically target tumors compared to normal cells, making them a promising therapeutic agent. The aptamer is a kind of short DNA or RNA sequence that can specifically bind to target molecules, and could be widely used as the active targeting agents of nanoplatforms to achieve active-targeted therapy of tumors. Herein, an aptamer modified nanoplatform DOX@PCN@Apt-M was designed for active-targeted chemo-photodynamic therapy of tumors. Zr-based porphyrinic nanoscale metal organic framework PCN-224 was synthesized through a one-pot reaction, which could produce cytotoxic 1O2 for efficient treatment of tumor cells. To improve the therapeutic effect of the tumor, the anticancer drug doxorubicin (DOX) was loaded into PCN-224 to form DOX@PCN-224 for tumor combination therapy. Active-targeted combination therapy achieved by modifying the MUC1 aptamer (Apt-M) onto DOX@PCN-224 surface can not only further reduce the dosage of therapeutic agents, but also reduce their toxic and side effects on normal tissues. In vitro, experimental results indicated that DOX@PCN@Apt-M exhibited enhanced combined therapeutic effect and active targeting efficiency under 808 nm laser irradiation for MCF-7 tumor cells. Based on PCN-224 nanocarriers and aptamer MUC1, this work provides a novel strategy for precisely targeting MCF-7 tumor cells.
Project description:Photodynamic therapy (PDT) is an alternative modality to conventional cancer treatment, whereby a specific wavelength of light is applied to a targeted tumor, which has either a photosensitizer or photochemotherapeutic agent localized within it. This light activates the photosensitizer in the presence of molecular oxygen to produce phototoxic species, which in turn obliterate cancer cells. The incidence rate of breast cancer (BC) is regularly growing among women, which are currently being treated with methods, such as chemotherapy, radiotherapy, and surgery. These conventional treatment methods are invasive and often produce unwanted side effects, whereas PDT is more specific and localized method of cancer treatment. The utilization of nanoparticles in PDT has shown great advantages compared to free photosensitizers in terms of solubility, early degradation, and biodistribution, as well as far more effective intercellular penetration and uptake in targeted cancer cells. This review gives an overview of the use of inorganic nanoparticles (NPs), including: gold, magnetic, carbon-based, ceramic, and up-conversion NPs, as well as quantum dots in PDT over the last 10 years (2009 to 2019), with a particular focus on the active targeting strategies for the PDT treatment of BC.
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:UiO-66 metal-organic framework nanoparticles (NMOFs) gated by aptamer-functionalized DNA tetrahedra provide superior biomarker-responsive hybrid nano-carriers for biomedical applications. Hybrid nano-carriers consisting of ATP-aptamer or VEGF-aptamer functionalized tetrahedra-gated NMOFs are loaded with the chemotherapeutic drug, doxorubicin (DOX). In the presence of ATP or VEGF, both abundant in cancer cells, the tetrahedra-gated NMOFs are unlocked to release the drug. Enhanced and selective permeation of the DOX-loaded ATP/VEGF-responsive tetrahedra-gated NMOFs into MDA-MB-231 breast cancer cells as compared to the reference ATP/VEGF-responsive duplex-gated NMOFs or non-malignant MCF-10A epithelial breast cells is observed. This results in enhanced and selective cytotoxicity of the tetrahedra-gated DOX-loaded NMOFs toward the malignant cells. Additional nano-carriers, consisting of photosensitizer Zn(ii) protoporphyrin IX (Zn(ii)-PPIX)-loaded VEGF-responsive tetrahedra-gated NMOFs, are introduced. The VEGF-triggered unlocking of the NMOFs yields separated G-quadruplex-VEGF aptamer complexes conjugated to the tetrahedra, resulting in the release of loaded Zn(ii)-PPIX. Association of the released Zn(ii)-PPIX to the G-quadruplex structures generates highly fluorescent supramolecular Zn(ii)-PPIX/G-quadruplex VEGF aptamer-tetrahedra structures. The efficient and selective generation of the highly fluorescent Zn(ii)-PPIX/G-quadruplex VEGF aptamer-tetrahedra nanostructures in malignant cells allows the light-induced photosensitized generation of reactive oxygen species (ROS), leading to high-efficacy PDT treatment of the malignant cells.
Project description:X-ray-induced photodynamic therapy is based on the energy transfer from a nanoscintillator to a photosensitizer molecule, whose activation leads to singlet oxygen and radical species generation, triggering cancer cells to cell death. Herein, we synthesized ultra-small nanoparticle chelated with Terbium (Tb) as a nanoscintillator and 5-(4-carboxyphenyl succinimide ester)-10,15,20-triphenyl porphyrin (P1) as a photosensitizer (AGuIX@Tb-P1). The synthesis was based on the AGuIX@ platform design. AGuIX@Tb-P1 was characterised for its photo-physical and physico-chemical properties. The effect of the nanoparticles was studied using human glioblastoma U-251 MG cells and was compared to treatment with AGuIX@ nanoparticles doped with Gadolinium (Gd) and P1 (AguIX@Gd-P1). We demonstrated that the AGuIX@Tb-P1 design was consistent with X-ray photon energy transfer from Terbium to P1. Both nanoparticles had similar dark cytotoxicity and they were absorbed in a similar rate within the cells. Pre-treated cells exposure to X-rays was related to reactive species production. Using clonogenic assays, establishment of survival curves allowed discrimination of the impact of radiation treatment from X-ray-induced photodynamic effect. We showed that cell growth arrest was increased (35%-increase) when cells were treated with AGuIX@Tb-P1 compared to the nanoparticle doped with Gd.
Project description:Interaction between tumour cells and macrophages enables cancer cells to evade immune detection and clearance by interfering with macrophage phagocytosis. The anti-phagocytic signals regulated by anti-phagocytic proteins are termed "don't eat me" signals; these signals include sialic acid-binding immunoglobulin-type lectin-10 (Siglec-10) and the recently revealed CD24 immune checkpoint (ICP). In this study, we demonstrate that targeting a specific glycan on CD24 exhibits the potential to inhibit ICP. Sambucus nigra agglutinin (SNA), a sialic acid-binding lectin, was employed to block CD24 and to enhance phagocytosis in melanoma tumours. In addition, we prepared SNA-conjugated hollow gold-iron oxide nanoparticles for photothermal therapy of tumours. Our findings show that the combination treatment of SNA-conjugated photothermal nanoparticles and near-infrared exposure successfully augments tumour cell phagocytosis both in vitro and in vivo models.
Project description:Herein, we report a nano-MOF conjugated to maltotriose as a new DDS. MA-PCN-224-0.1Mn/0.9Zn showed its ability to target cancer and TAM. This novel MOF is an effective PDT agent and shows little dark toxicity, MA-PCN-224-0.1Mn/0.9Zn uptakes selectively into cancer cells. A well-suited size control methodology was used so that the nano-scaled MOFs may take advantage of the EPR effect. This development of a nano-scale MOF for PDT that is conjugated to a cancer targeting ligand represents a meaningful development for the use of MOFs as drug delivery systems.
Project description:Photodynamic therapy (PDT) is believed to promote hypoxic conditions to tumor cells leading to overexpression of angiogenic markers such as vascular endothelial growth factor (VEGF). In this study, PDT was combined with lipid-calcium-phosphate nanoparticles (LCP NPs) to deliver VEGF-A small interfering RNA (siVEGF-A) to human head and neck squamous cell carcinoma (HNSCC) xenograft models. VEGF-A were significantly decreased for groups treated with siVEGF-A in human oral squamous cancer cell (HOSCC), SCC4 and SAS models. Cleaved caspase-3 and in situ TdT-mediated dUTP nick-end labeling assay showed more apoptotic cells and reduced Ki-67 expression for treated groups compared to phosphate buffered saline (PBS) group. Indeed, the combined therapy showed significant tumor volume decrease to ~70 and ~120% in SCC4 and SAS models as compared with untreated PBS group, respectively. In vivo toxicity study suggests no toxicity of such LCP NP delivered siVEGF-A. In summary, results suggest that PDT combined with targeted VEGF-A gene therapy could be a potential therapeutic modality to achieve enhanced therapeutic outcome for HNSCC.
Project description:Photodynamic therapy combining nanotechnology has shown great potential with improved therapeutic efficacy and fewer side effects. Ideal photosensitizers for cancer treatment should both have good singlet oxygen production capability and be excitable by light illuminations with deep tissue penetration. Here we report a type of hybrid photosensitizers consisting of plasmonic silver nanoparticles and photosensitizing molecules, where strong resonance coupling between the two leads to a broadened excitation profile and exceptionally high singlet oxygen production under both visible light and infrared light excitations. Our results indicate that the hybrid photosensitizers display low cytotoxicity without light illumination yet highly enhanced photodynamic inhibition efficacy against Hela cells under a broad spectrum of light illuminations including the near-infrared light, which has great implication in photodynamic therapy of deep-tissue cancers.