Enhancing doxorubicin anticancer activity with a novel polymeric platform photoreleasing nitric oxide

Research output: Contribution to journalArticlepeer-review

Standard

Enhancing doxorubicin anticancer activity with a novel polymeric platform photoreleasing nitric oxide. / Sodano, Federica; Cavanagh, Robert J.; Pearce, Amanda K.; Lazzarato, Loretta; Rolando, Barbara; Fraix, Aurore; Abelha, Thais F.; Vasey, Catherine E.; Alexander, Cameron; Taresco, Vincenzo; Sortino, Salvatore.

In: Biomaterials Science, Vol. 8, No. 5, 07.03.2020, p. 1329-1344.

Research output: Contribution to journalArticlepeer-review

Harvard

Sodano, F, Cavanagh, RJ, Pearce, AK, Lazzarato, L, Rolando, B, Fraix, A, Abelha, TF, Vasey, CE, Alexander, C, Taresco, V & Sortino, S 2020, 'Enhancing doxorubicin anticancer activity with a novel polymeric platform photoreleasing nitric oxide', Biomaterials Science, vol. 8, no. 5, pp. 1329-1344. https://doi.org/10.1039/c9bm01644a

APA

Sodano, F., Cavanagh, R. J., Pearce, A. K., Lazzarato, L., Rolando, B., Fraix, A., Abelha, T. F., Vasey, C. E., Alexander, C., Taresco, V., & Sortino, S. (2020). Enhancing doxorubicin anticancer activity with a novel polymeric platform photoreleasing nitric oxide. Biomaterials Science, 8(5), 1329-1344. https://doi.org/10.1039/c9bm01644a

Vancouver

Author

Sodano, Federica ; Cavanagh, Robert J. ; Pearce, Amanda K. ; Lazzarato, Loretta ; Rolando, Barbara ; Fraix, Aurore ; Abelha, Thais F. ; Vasey, Catherine E. ; Alexander, Cameron ; Taresco, Vincenzo ; Sortino, Salvatore. / Enhancing doxorubicin anticancer activity with a novel polymeric platform photoreleasing nitric oxide. In: Biomaterials Science. 2020 ; Vol. 8, No. 5. pp. 1329-1344.

Bibtex

@article{ab71b2e9a6544d7cac51c0bcbe585eb3,
title = "Enhancing doxorubicin anticancer activity with a novel polymeric platform photoreleasing nitric oxide",
abstract = "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.",
author = "Federica Sodano and Cavanagh, {Robert J.} and Pearce, {Amanda K.} and Loretta Lazzarato and Barbara Rolando and Aurore Fraix and Abelha, {Thais F.} and Vasey, {Catherine E.} and Cameron Alexander and Vincenzo Taresco and Salvatore Sortino",
year = "2020",
month = mar,
day = "7",
doi = "10.1039/c9bm01644a",
language = "English",
volume = "8",
pages = "1329--1344",
journal = "Biomaterials Science",
issn = "2047-4830",
publisher = "Royal Society of Chemistry",
number = "5",

}

RIS

TY - JOUR

T1 - Enhancing doxorubicin anticancer activity with a novel polymeric platform photoreleasing nitric oxide

AU - Sodano, Federica

AU - Cavanagh, Robert J.

AU - Pearce, Amanda K.

AU - Lazzarato, Loretta

AU - Rolando, Barbara

AU - Fraix, Aurore

AU - Abelha, Thais F.

AU - Vasey, Catherine E.

AU - Alexander, Cameron

AU - Taresco, Vincenzo

AU - Sortino, Salvatore

PY - 2020/3/7

Y1 - 2020/3/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85081134249&partnerID=8YFLogxK

U2 - 10.1039/c9bm01644a

DO - 10.1039/c9bm01644a

M3 - Article

C2 - 31912808

AN - SCOPUS:85081134249

VL - 8

SP - 1329

EP - 1344

JO - Biomaterials Science

JF - Biomaterials Science

SN - 2047-4830

IS - 5

ER -