Biodegradable nanoparticles exposing a short anti-FLT1 peptide as antiangiogenic platform to complement docetaxel anticancer activity (203 views)
Mater Sci Eng C Mater Biol Appl (ISSN: 0928-4931linking), 2019 Sep; 102: 876-886.
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Paper type: Journal Article,
Impact factor: 5.08, 5-year impact factor: 0
Url: Not available.
Keywords: Angiogenesis Inhibitors Pharmacology , Animals , Antineoplastic Agents Pharmacology , Biocompatible Materials Pharmacology , Cell Death Drug Effects , Cell Line, Tumor , Cell Membrane Drug Effects Metabolism , Chickens , Chorioallantoic Membrane Drug Effects Metabolism , Docetaxel Pharmacology , Human Umbilical Vein Endothelial Cells Drug Effects Metabolism , Nanoparticles Chemistry , Neovascularization, Physiologic Drug Effects , Peptides Chemistry , Polyesters Chemical Synthesis Chemistry , Polyethylene Glycols Chemical Synthesis Chemistry , Vascular Endothelial Growth Factor Receptor-1 Metabolism,
Affiliations:
*** IBB - CNR ***
Department of Pharmacy, University of Napoli Federico II, Italy.
Department of Biology, University of Padova, Italy.
Institute for Polymers, Composites and Biomaterials, CNR, Pozzuoli, Napoli, Italy.
Institute of Biostructure and Bioimaging, CNR, Napoli, Italy.
References:
Not available.
Mater Sci Eng C Mater Biol Appl (ISSN: 0928-4931linking), 2019 Sep; 102: 876-886.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 5.08, 5-year impact factor: 0
Url: Not available.
Keywords: Angiogenesis Inhibitors Pharmacology , Animals , Antineoplastic Agents Pharmacology , Biocompatible Materials Pharmacology , Cell Death Drug Effects , Cell Line, Tumor , Cell Membrane Drug Effects Metabolism , Chickens , Chorioallantoic Membrane Drug Effects Metabolism , Docetaxel Pharmacology , Human Umbilical Vein Endothelial Cells Drug Effects Metabolism , Nanoparticles Chemistry , Neovascularization, Physiologic Drug Effects , Peptides Chemistry , Polyesters Chemical Synthesis Chemistry , Polyethylene Glycols Chemical Synthesis Chemistry , Vascular Endothelial Growth Factor Receptor-1 Metabolism,
Affiliations:
*** IBB - CNR ***
Department of Pharmacy, University of Napoli Federico II, Italy.
Department of Biology, University of Padova, Italy.
Institute for Polymers, Composites and Biomaterials, CNR, Pozzuoli, Napoli, Italy.
Institute of Biostructure and Bioimaging, CNR, Napoli, Italy.
References:
Not available.
Biodegradable nanoparticles exposing a short anti-FLT1 peptide as antiangiogenic platform to complement docetaxel anticancer activity
Inhibition of tumor angiogenesis is considered as a valuable clinical strategy to treat some tumors, although benefits in term of progression-free and overall survival have been modest. Recent findings have pushed toward the use of antiangiogenic drugs in combination with chemotherapy regimens to potentiate therapeutic outcome. Herein, we propose a novel type of biodegradable antiangiogenic core-shell polymeric nanoparticles (NPs) for the delivery of poorly water-soluble chemotherapeutics. An amphiphilic diblock copolymer of poly(ethyleneglycol)-poly(ε-caprolactone) (PEG-PCL) was conjugated with an anti-FLT1 hexapeptide (aFLT1) at -OH PEG end, mixed in appropriate ratios with a monomethoxy-PEG-PCL and nanoprecipitated to form core-shell aFLT1-bearing NPs (DBL(aFLT1)). DBL(aFLT1) were <100 nm, exposed aFLT1 on the surface and showed a higher thickness of the external hydrophilic shell as compared to NPs that do not bear aFLT1 (DBL). Very interestingly, DBL(aFLT1) showed an antiangiogenic activity in the human umbilical endothelial cells (HUVEC) tube formation assay three-fold higher than an equivalent dose of free aFLT1. To provide a proof-of-concept of DBL(aFLT1) potential in the delivery of conventional chemotherapeutics, docetaxel (DTX) was selected as model drug. DBL(aFLT1) entrapped DTX with high efficiency and sustained its release along time in simulated biological conditions. At a non-cytotoxic dose, DTX-loaded DBL(aFLT1) almost completely abolished tube formation in HUVEC while inhibition of DTX loaded DBL was significantly lower. The cytotoxicity of DTX-loaded NPs in HUVEC and triple negative breast cancer cells (MDA-MB-231) was not significantly different from that of the free drug in a wide range of concentrations and up to 72 h. Studies carried out in MDA-MB-231 cells implanted in chicken embryo chorioallantoic membranes (CAMs) evidenced an antiangiogenic activity of DTX-loaded DBL(aFLT1) higher as compared with that of both DTX-loaded DBL and free DTX. While cancer cell migration from the tumor site was unaffected, the anticancer activity of DTX-loaded NPs was higher than that of free DTX and maximized for DTX-DBL(aFLT1). In perspective, these results suggest that the delivery approach proposed here can be applied to other lipophilic chemotherapeutics devoid of relevant antiangiogenic properties to improve the final therapeutic response.
Inhibition of tumor angiogenesis is considered as a valuable clinical strategy to treat some tumors, although benefits in term of progression-free and overall survival have been modest. Recent findings have pushed toward the use of antiangiogenic drugs in combination with chemotherapy regimens to potentiate therapeutic outcome. Herein, we propose a novel type of biodegradable antiangiogenic core-shell polymeric nanoparticles (NPs) for the delivery of poorly water-soluble chemotherapeutics. An amphiphilic diblock copolymer of poly(ethyleneglycol)-poly(ε-caprolactone) (PEG-PCL) was conjugated with an anti-FLT1 hexapeptide (aFLT1) at -OH PEG end, mixed in appropriate ratios with a monomethoxy-PEG-PCL and nanoprecipitated to form core-shell aFLT1-bearing NPs (DBL(aFLT1)). DBL(aFLT1) were <100 nm, exposed aFLT1 on the surface and showed a higher thickness of the external hydrophilic shell as compared to NPs that do not bear aFLT1 (DBL). Very interestingly, DBL(aFLT1) showed an antiangiogenic activity in the human umbilical endothelial cells (HUVEC) tube formation assay three-fold higher than an equivalent dose of free aFLT1. To provide a proof-of-concept of DBL(aFLT1) potential in the delivery of conventional chemotherapeutics, docetaxel (DTX) was selected as model drug. DBL(aFLT1) entrapped DTX with high efficiency and sustained its release along time in simulated biological conditions. At a non-cytotoxic dose, DTX-loaded DBL(aFLT1) almost completely abolished tube formation in HUVEC while inhibition of DTX loaded DBL was significantly lower. The cytotoxicity of DTX-loaded NPs in HUVEC and triple negative breast cancer cells (MDA-MB-231) was not significantly different from that of the free drug in a wide range of concentrations and up to 72 h. Studies carried out in MDA-MB-231 cells implanted in chicken embryo chorioallantoic membranes (CAMs) evidenced an antiangiogenic activity of DTX-loaded DBL(aFLT1) higher as compared with that of both DTX-loaded DBL and free DTX. While cancer cell migration from the tumor site was unaffected, the anticancer activity of DTX-loaded NPs was higher than that of free DTX and maximized for DTX-DBL(aFLT1). In perspective, these results suggest that the delivery approach proposed here can be applied to other lipophilic chemotherapeutics devoid of relevant antiangiogenic properties to improve the final therapeutic response.
Biodegradable nanoparticles exposing a short anti-FLT1 peptide as antiangiogenic platform to complement docetaxel anticancer activity
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Biodegradable nanoparticles exposing a short anti-FLT1 peptide as antiangiogenic platform to complement docetaxel anticancer activity
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8 Records (8 excluding Abstracts).
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203 views. Last view on Thursday 06 October 2022, 13:20:31
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