TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=85141848714&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000881227500001&DestLinkType=FullRecord&DestApp=WOS_CPL
UR - http://hdl.handle.net/20.500.14342/4458
U2 - 10.3390/ijms232112817
DO - 10.3390/ijms232112817
M3 - Article
C2 - 36361615
AN - SCOPUS:85141848714
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 21
M1 - 12817
ER -
