Dual-Functionalized Nanoliposomes Achieve a Synergistic Chemo-Phototherapeutic Effect

Ana Lazaro-Carrillo; Beatriz Rodríguez-Amigo; Margarita Mora; Maria Lluïsa Sagristá; Magdalena Cañete; Santi Nonell; Angeles Villanueva

doi:10.3390/ijms232112817

Dual-Functionalized Nanoliposomes Achieve a Synergistic Chemo-Phototherapeutic Effect

Ana Lazaro-Carrillo
, Beatriz Rodríguez-Amigo
, Margarita Mora
, Maria Lluïsa Sagristá
, Magdalena Cañete
, Santi Nonell^*
, Angeles Villanueva^*

^*Corresponding author for this work

Research output: Indexed journal article › Article › peer-review

2 Citations (Scopus)

Abstract

The enhancement of photodynamic therapy (PDT) effectiveness by combining it with other treatment modalities and improved drug delivery has become an interesting field in cancer research. We have prepared and characterized nanoliposomes containing the chemotherapeutic drug irinotecan (CPT11_lip), the photodynamic agent protoporphyrin IX (PpIX_lip), or their combination (CPT11-PpIX_lip). The effects of individual and bimodal (chemo-phototherapeutic) treatments on HeLa cells have been studied by a combination of biological and photophysical studies. Bimodal treatments show synergistic cytotoxic effects on HeLa cells at relatively low doses of PpIX/PDT and CPT11. Mechanistic cell inactivation studies revealed mitotic catastrophe, apoptosis, and senescence contributions. The enhanced anticancer activity is due to a sustained generation of reactive oxygen species, which increases the number of double-strand DNA breaks. Bimodal chemo-phototherapeutic liposomes may have a very promising future in oncological therapy, potentially allowing a reduction in the CPT11 concentration required to achieve a therapeutic effect and overcoming resistance to individual cancer treatments.

Original language	English
Article number	12817
Number of pages	19
Journal	International Journal of Molecular Sciences
Volume	23
Issue number	21
DOIs	https://doi.org/10.3390/ijms232112817
Publication status	Published - Nov 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

bimodal-functionalized nanoliposomes
chemo-phototherapy
double-strand DNA break
irinotecan
photodynamic therapy
protoporphyrin IX
reactive oxygen species
subcellular location
synergistic effect
time-lapse microscopy

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10.3390/ijms232112817Licence: CC BY

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@article{532cc9e3b80d4460bbaff0741c92c90b,

title = "Dual-Functionalized Nanoliposomes Achieve a Synergistic Chemo-Phototherapeutic Effect",

abstract = "The enhancement of photodynamic therapy (PDT) effectiveness by combining it with other treatment modalities and improved drug delivery has become an interesting field in cancer research. We have prepared and characterized nanoliposomes containing the chemotherapeutic drug irinotecan (CPT11lip), the photodynamic agent protoporphyrin IX (PpIXlip), or their combination (CPT11-PpIXlip). The effects of individual and bimodal (chemo-phototherapeutic) treatments on HeLa cells have been studied by a combination of biological and photophysical studies. Bimodal treatments show synergistic cytotoxic effects on HeLa cells at relatively low doses of PpIX/PDT and CPT11. Mechanistic cell inactivation studies revealed mitotic catastrophe, apoptosis, and senescence contributions. The enhanced anticancer activity is due to a sustained generation of reactive oxygen species, which increases the number of double-strand DNA breaks. Bimodal chemo-phototherapeutic liposomes may have a very promising future in oncological therapy, potentially allowing a reduction in the CPT11 concentration required to achieve a therapeutic effect and overcoming resistance to individual cancer treatments.",

keywords = "bimodal-functionalized nanoliposomes, chemo-phototherapy, double-strand DNA break, irinotecan, photodynamic therapy, protoporphyrin IX, reactive oxygen species, subcellular location, synergistic effect, time-lapse microscopy",

author = "Ana Lazaro-Carrillo and Beatriz Rodr{\'i}guez-Amigo and Margarita Mora and Sagrist{\'a}, \{Maria Llu{\"i}sa\} and Magdalena Ca{\~n}ete and Santi Nonell and Angeles Villanueva",

note = "Funding Information: This research was funded by the Spanish Ministry of Economy and Competitiveness, grant numbers CTQ2016-78454-C2-1-R, CTQ2016-78454-C2-2-R, and PID2020-115801RB-C22/MICIN/AEI/10.13039/501100011033. A.L.-C. acknowledges financial support from UAM (Teaching Assistant contract 20140513-136) and IMDEA Nanociencia acknowledges support from the “Severo Ochoa” Programme for Centres of Excellence in R\&D (MINECO, Grant SEV-2016-0686). Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = nov,

doi = "10.3390/ijms232112817",

language = "English",

volume = "23",

journal = "International Journal of Molecular Sciences",

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number = "21",

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T1 - Dual-Functionalized Nanoliposomes Achieve a Synergistic Chemo-Phototherapeutic Effect

AU - Lazaro-Carrillo, Ana

AU - Rodríguez-Amigo, Beatriz

AU - Mora, Margarita

AU - Sagristá, Maria Lluïsa

AU - Cañete, Magdalena

AU - Nonell, Santi

AU - Villanueva, Angeles

N1 - Funding Information: This research was funded by the Spanish Ministry of Economy and Competitiveness, grant numbers CTQ2016-78454-C2-1-R, CTQ2016-78454-C2-2-R, and PID2020-115801RB-C22/MICIN/AEI/10.13039/501100011033. A.L.-C. acknowledges financial support from UAM (Teaching Assistant contract 20140513-136) and IMDEA Nanociencia acknowledges support from the “Severo Ochoa” Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686). Publisher Copyright: © 2022 by the authors.

PY - 2022/11

Y1 - 2022/11

N2 - The enhancement of photodynamic therapy (PDT) effectiveness by combining it with other treatment modalities and improved drug delivery has become an interesting field in cancer research. We have prepared and characterized nanoliposomes containing the chemotherapeutic drug irinotecan (CPT11lip), the photodynamic agent protoporphyrin IX (PpIXlip), or their combination (CPT11-PpIXlip). The effects of individual and bimodal (chemo-phototherapeutic) treatments on HeLa cells have been studied by a combination of biological and photophysical studies. Bimodal treatments show synergistic cytotoxic effects on HeLa cells at relatively low doses of PpIX/PDT and CPT11. Mechanistic cell inactivation studies revealed mitotic catastrophe, apoptosis, and senescence contributions. The enhanced anticancer activity is due to a sustained generation of reactive oxygen species, which increases the number of double-strand DNA breaks. Bimodal chemo-phototherapeutic liposomes may have a very promising future in oncological therapy, potentially allowing a reduction in the CPT11 concentration required to achieve a therapeutic effect and overcoming resistance to individual cancer treatments.

AB - The enhancement of photodynamic therapy (PDT) effectiveness by combining it with other treatment modalities and improved drug delivery has become an interesting field in cancer research. We have prepared and characterized nanoliposomes containing the chemotherapeutic drug irinotecan (CPT11lip), the photodynamic agent protoporphyrin IX (PpIXlip), or their combination (CPT11-PpIXlip). The effects of individual and bimodal (chemo-phototherapeutic) treatments on HeLa cells have been studied by a combination of biological and photophysical studies. Bimodal treatments show synergistic cytotoxic effects on HeLa cells at relatively low doses of PpIX/PDT and CPT11. Mechanistic cell inactivation studies revealed mitotic catastrophe, apoptosis, and senescence contributions. The enhanced anticancer activity is due to a sustained generation of reactive oxygen species, which increases the number of double-strand DNA breaks. Bimodal chemo-phototherapeutic liposomes may have a very promising future in oncological therapy, potentially allowing a reduction in the CPT11 concentration required to achieve a therapeutic effect and overcoming resistance to individual cancer treatments.

KW - bimodal-functionalized nanoliposomes

KW - chemo-phototherapy

KW - double-strand DNA break

KW - irinotecan

KW - photodynamic therapy

KW - protoporphyrin IX

KW - reactive oxygen species

KW - subcellular location

KW - synergistic effect

KW - time-lapse microscopy

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SN - 1661-6596

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JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

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ER -

Dual-Functionalized Nanoliposomes Achieve a Synergistic Chemo-Phototherapeutic Effect

Abstract

UN SDGs

Keywords

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