دورية أكاديمية
Enhancing doxorubicin anticancer activity with a novel polymeric platform photoreleasing nitric oxide.
| العنوان: | Enhancing doxorubicin anticancer activity with a novel polymeric platform photoreleasing nitric oxide. |
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| المؤلفون: | Sodano F; Department of Drug Science and Technology, University of Turin, 10125, Turin, Italy. federica.sodano@unito.it., Cavanagh RJ, Pearce AK, Lazzarato L, Rolando B, Fraix A, Abelha TF, Vasey CE, Alexander C, Taresco V, Sortino S |
| المصدر: | Biomaterials science [Biomater Sci] 2020 Mar 07; Vol. 8 (5), pp. 1329-1344. Date of Electronic Publication: 2020 Jan 08. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101593571 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2047-4849 (Electronic) Linking ISSN: 20474830 NLM ISO Abbreviation: Biomater Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, UK : Royal Society of Chemistry |
| مواضيع طبية MeSH: | Antibiotics, Antineoplastic/*pharmacology , Doxorubicin/*pharmacology , Nanoparticles/*chemistry , Nitric Oxide/*metabolism , Nitric Oxide Donors/*pharmacology , Polymers/*chemistry, Antibiotics, Antineoplastic/chemical synthesis ; Antibiotics, Antineoplastic/chemistry ; Cell Line ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Doxorubicin/chemical synthesis ; Doxorubicin/chemistry ; Drug Screening Assays, Antitumor ; Humans ; Nitric Oxide Donors/chemical synthesis ; Nitric Oxide Donors/chemistry ; Photochemical Processes ; Structure-Activity Relationship |
| مستخلص: | Combinations of conventional chemotherapeutics with unconventional anticancer agents such as reactive oxygen and nitrogen species may offer treatment benefits for cancer therapies. Here we report a novel polymeric platform combining the delivery of Doxorubicin (DOXO) with the light-regulated release of nitric oxide (NO). An amphiphilic block-copolymer (P1) was designed and synthesized as the drug carrier, with pendant amine groups to attach DOXO via a urea linkage and a NO photodonor (NOPD) activable by visible light. The two grafted-copolymers (P1-DOXO and P1-NOPD) self-assembled via solvent displacement methods into nanoparticles (NPs), containing both therapeutic components (NP1) and, for comparison, the individual NOPD (NP2) and DOXO (NP3). All the NPs were fully characterized in terms of physicochemical, photochemical and photophysical properties. These experiments demonstrated that integration of the NOPD within the polymeric scaffold enhanced the NO photoreleasing efficiency when compared with the free NOPD, and that the proximity to DOXO on the polymer chains did not significantly affect the enhanced photochemical performance. Internalization of the NPs into lung, intestine, and skin cancer cell lines was investigated after co-formulation with Cy5 fluorescent tagged polymers, and cytotoxicity of the NPs against the same panel of cell lines was assessed under dark and light conditions. The overall results demonstrate effective cell internalization of the NPs and a notable enhancement in killing activity of the dual-action therapeutic NP1 when compared with NP2, NP3 and the free DOXO, respectively. This suggests that the combination of DOXO with photoregulated NO release, achieved through the mixed formulation strategy of tailored polymer conjugate NPs, may open new treatment modalities based on the use of NO to improve cancer therapies. |
| المشرفين على المادة: | 0 (Antibiotics, Antineoplastic) 0 (Nitric Oxide Donors) 0 (Polymers) 31C4KY9ESH (Nitric Oxide) 80168379AG (Doxorubicin) |
| تواريخ الأحداث: | Date Created: 20200109 Date Completed: 20201123 Latest Revision: 20201123 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1039/c9bm01644a |
| PMID: | 31912808 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2047-4849 |
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| DOI: | 10.1039/c9bm01644a |