Nanotechnologies grounded on cyclodextrin (CyD)-based polymeric nanoparticles (NPs) have beenaccurately tailored in order to improve the pharmaco-kinetic and dynamic profiles of conventionaldrugs and to load in a single, biocompatible carrier multiple therapeutic agents to achieve specifictumor tissue targeting [1]. Light-activated therapies are receiving increasing attention for thetreatment of solid tumors, including Breast Cancer (BC). Photodynamic therapy (PDT) consists inthe administration of a photosensitizer (PS) which produces reactive oxygen species (ROS) i.e.singletoxygen (1O2), upon irradiation with red light in the presence of molecular oxygen (O2), triggering acascade of processes eventually killing cancer cells. Yet, tumor cells can undergo tissue hypoxia,such as an inadequate supply of O2, which will reduce PDT efficacy [2], and activate molecularpathways inducing resistance to chemotherapy (i.e. taxanes)[3].The HypoCyclo project aims to optimize a novel combination of chemo- and photo-therapy for theselective and effective treatment of BC. CyD-based NPs able to load taxanes will be decorated witha PS i.e. Chlorin e6 (Ce6) and implemented with an Oxygen Releasing Agent (ORA) that will supplyO2 in situ [4].We synthesized four anthracene and naphthalene derivatives known as suitable ORA because of theircapacity to form endoperoxide moieties by trapping 1O2 and their exceptional ability of releasing itupon controlled cycloreversion5. The synthesis has been achieved after optimization of publishedprocedures. We started to study photooxygenation conditions with 9,10-diphenylanthracene (DPA)as reference compound and the obtained product was fully characterized by NMR, IR and UV-Visspectroscopies and ESI-MS spectrometry. In parallel, we successfully entrapped Ce6 in the CyDbased NPs with a binding constant of 103 M-1 without affecting its ability to generate 1O2 in deuteratedbuffer solution. At the moment, we are optimizing the photooxygenation procedures for thesynthesized derivatives as well as their encapsulation in the polymeric carrier together with Ce6.Upon co-encapsulation molecular oxygen release will be evaluated
Photochemical synthesis and preliminary photophysical evaluation of a multi-component polymer enabling PDT in hypoxic conditions as novel Breast Cancer treatment
M Agnes
Primo
Conceptualization
;F Manoli;I Manet
Ultimo
Conceptualization
2021
Abstract
Nanotechnologies grounded on cyclodextrin (CyD)-based polymeric nanoparticles (NPs) have beenaccurately tailored in order to improve the pharmaco-kinetic and dynamic profiles of conventionaldrugs and to load in a single, biocompatible carrier multiple therapeutic agents to achieve specifictumor tissue targeting [1]. Light-activated therapies are receiving increasing attention for thetreatment of solid tumors, including Breast Cancer (BC). Photodynamic therapy (PDT) consists inthe administration of a photosensitizer (PS) which produces reactive oxygen species (ROS) i.e.singletoxygen (1O2), upon irradiation with red light in the presence of molecular oxygen (O2), triggering acascade of processes eventually killing cancer cells. Yet, tumor cells can undergo tissue hypoxia,such as an inadequate supply of O2, which will reduce PDT efficacy [2], and activate molecularpathways inducing resistance to chemotherapy (i.e. taxanes)[3].The HypoCyclo project aims to optimize a novel combination of chemo- and photo-therapy for theselective and effective treatment of BC. CyD-based NPs able to load taxanes will be decorated witha PS i.e. Chlorin e6 (Ce6) and implemented with an Oxygen Releasing Agent (ORA) that will supplyO2 in situ [4].We synthesized four anthracene and naphthalene derivatives known as suitable ORA because of theircapacity to form endoperoxide moieties by trapping 1O2 and their exceptional ability of releasing itupon controlled cycloreversion5. The synthesis has been achieved after optimization of publishedprocedures. We started to study photooxygenation conditions with 9,10-diphenylanthracene (DPA)as reference compound and the obtained product was fully characterized by NMR, IR and UV-Visspectroscopies and ESI-MS spectrometry. In parallel, we successfully entrapped Ce6 in the CyDbased NPs with a binding constant of 103 M-1 without affecting its ability to generate 1O2 in deuteratedbuffer solution. At the moment, we are optimizing the photooxygenation procedures for thesynthesized derivatives as well as their encapsulation in the polymeric carrier together with Ce6.Upon co-encapsulation molecular oxygen release will be evaluatedFile | Dimensione | Formato | |
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