Comparative analysis of whole cell-derived vesicular delivery systems for photodynamic therapy of extrahepatic cholangiocarcinoma

on behalf of the Photodynamic Therapy Study Group

doi:10.1016/j.jphotobiol.2024.112903

Comparative analysis of whole cell-derived vesicular delivery systems for photodynamic therapy of extrahepatic cholangiocarcinoma

on behalf of the Photodynamic Therapy Study Group

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

This first-in-its-class proof-of-concept study explored the use of bionanovesicles for the delivery of photosensitizer into cultured cholangiocarcinoma cells and subsequent treatment by photodynamic therapy (PDT). Two types of bionanovesicles were prepared: cellular vesicles (CVs) were fabricated by sonication-mediated nanosizing of cholangiocarcinoma (TFK-1) cells, whereas cell membrane vesicles (CMVs) were produced by TFK-1 cell and organelle membrane isolation and subsequent nanovesicularization by sonication. The bionanovesicles were loaded with zinc phthalocyanine (ZnPC). The CVs and CMVs were characterized (size, polydispersity index, zeta potential, stability, ZnPC encapsulation efficiency, spectral properties) and assayed for tumor (TFK-1) cell association and uptake (flow cytometry, confocal microscopy), intracellular ZnPC distribution (confocal microscopy), dark toxicity (MTS assay), and PDT efficacy (MTS assay). The mean ± SD diameter, polydispersity index, and zeta potential were 134 ± 1 nm, −16.1 ± 0.9, and 0.220 ± 0.013, respectively, for CVs and 172 ± 3 nm, −16.4 ± 1.1, and 0.167 ± 0.022, respectively, for CMVs. Cold storage for 1 wk and incorporation of ZnPC increased bionanovesicular diameter slightly but size remained within the recommended range for in vivo application (136–220 nm). ZnPC was incorporated into CVs and CMVs at an optimal photosensitizer:lipid molar ratio of 0.006 and 0.01, respectively. Both bionanovesicles were avidly taken up by TFK-1 cells, resulting in homogenous intracellular ZnPC dispersion. Photosensitization of TFK-1 cells did not cause dark toxicity, while illumination at 671 nm (35.3 J/cm²) produced LC₅₀ values of 1.11 μM (CVs) and 0.51 μM (CMVs) at 24 h post-PDT, which is superior to most LC₅₀ values generated in tumor cells photosensitized with liposomal ZnPC. In conclusion, CVs and CMVs constitute a potent photosensitizer platform with no inherent cytotoxicity and high PDT efficacy in vitro.

Original language	English
Article number	112903
Journal	Journal of Photochemistry and Photobiology B: Biology
Volume	254
DOIs	https://doi.org/10.1016/j.jphotobiol.2024.112903
Publication status	Published - May 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Funding

This research was funded by grants from the Dutch Cancer Foundation (KWF project # 10666), a Zhejiang Provincial Foreign Expert Program Grant, Zhejiang Provincial Key Natural Science Foundation of China (#Z20H160031), a Basic Public Welfare Research Project of Zhejiang Province (LGD21H300001), and a Science and Technology Planning Project of Jiaxing City, Zhejiang Province (2019AY32012). WP was sponsored by a grant from the National Natural Science Foundation of China (31871402). HS received financial support from the National Natural Science Foundation of China. YSK was supported by the Academy of Medical Sciences (SGL027/1011). ML was supported by a Chinese Scholarship Council grant (202108330069).Michal Heger reports financial support was provided by Dutch Cancer Society. Michal Heger reports financial support was provided by Zhejiang Provincial Key Natural Science Foundation of China. Michal Heger reports financial support was provided by Basic Public Welfare Research Project of Zhejiang Province. Mingjuan Li reports financial support was provided by Science and Technology Planning Project of Jiaxing City, Zhejiang Province. Weiwei Pan reports financial support was provided by National Natural Science Foundation of China. Yazan S. Khaled reports financial support was provided by Academy of Medical Sciences. Mingjuan Li reports financial support was provided by Chinese Scholarship Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Funders	Funder number
Zhejiang Provincial Foreign Expert Program
Science and Technology Planning Project of Jiaxing City
Cancer Couch Foundation
KWF Kankerbestrijding	10666
KWF Kankerbestrijding
Academy of Medical Sciences	SGL027/1011
Academy of Medical Sciences
Zhejiang Provincial Key Natural Science Foundation of China	Z20H160031
China Scholarship Council	202108330069
China Scholarship Council
Zhejiang Province	2019AY32012
Basic Public Welfare Research Program of Zhejiang Province	LGD21H300001
Basic Public Welfare Research Program of Zhejiang Province
National Natural Science Foundation of China	31871402
National Natural Science Foundation of China

Keywords

Anti-cancer treatment
Biliary tumors
Cell death
Endocytosis
Intracellular distribution
Oxidative stress
Photosensitized
Reactive oxygen species
Targeted photosensitizer delivery
Vesicles

UN SDGs

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

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10.1016/j.jphotobiol.2024.112903Licence: CC BY

1-s2.0-S1011134424000630-mainFinal published version, 10.7 MBLicence: CC BY

Cite this

@article{1f0eab6ce7924ef9b7bc2f869b791f85,

title = "Comparative analysis of whole cell-derived vesicular delivery systems for photodynamic therapy of extrahepatic cholangiocarcinoma",

abstract = "This first-in-its-class proof-of-concept study explored the use of bionanovesicles for the delivery of photosensitizer into cultured cholangiocarcinoma cells and subsequent treatment by photodynamic therapy (PDT). Two types of bionanovesicles were prepared: cellular vesicles (CVs) were fabricated by sonication-mediated nanosizing of cholangiocarcinoma (TFK-1) cells, whereas cell membrane vesicles (CMVs) were produced by TFK-1 cell and organelle membrane isolation and subsequent nanovesicularization by sonication. The bionanovesicles were loaded with zinc phthalocyanine (ZnPC). The CVs and CMVs were characterized (size, polydispersity index, zeta potential, stability, ZnPC encapsulation efficiency, spectral properties) and assayed for tumor (TFK-1) cell association and uptake (flow cytometry, confocal microscopy), intracellular ZnPC distribution (confocal microscopy), dark toxicity (MTS assay), and PDT efficacy (MTS assay). The mean ± SD diameter, polydispersity index, and zeta potential were 134 ± 1 nm, −16.1 ± 0.9, and 0.220 ± 0.013, respectively, for CVs and 172 ± 3 nm, −16.4 ± 1.1, and 0.167 ± 0.022, respectively, for CMVs. Cold storage for 1 wk and incorporation of ZnPC increased bionanovesicular diameter slightly but size remained within the recommended range for in vivo application (136–220 nm). ZnPC was incorporated into CVs and CMVs at an optimal photosensitizer:lipid molar ratio of 0.006 and 0.01, respectively. Both bionanovesicles were avidly taken up by TFK-1 cells, resulting in homogenous intracellular ZnPC dispersion. Photosensitization of TFK-1 cells did not cause dark toxicity, while illumination at 671 nm (35.3 J/cm2) produced LC50 values of 1.11 μM (CVs) and 0.51 μM (CMVs) at 24 h post-PDT, which is superior to most LC50 values generated in tumor cells photosensitized with liposomal ZnPC. In conclusion, CVs and CMVs constitute a potent photosensitizer platform with no inherent cytotoxicity and high PDT efficacy in vitro.",

keywords = "Anti-cancer treatment, Biliary tumors, Cell death, Endocytosis, Intracellular distribution, Oxidative stress, Photosensitized, Reactive oxygen species, Targeted photosensitizer delivery, Vesicles",

author = "\{on behalf of the Photodynamic Therapy Study Group\} and Mingjuan Li and Bosman, \{Esmeralda D.C.\} and Smith, \{Olivia M.\} and Nicole Lintern and \{de Klerk\}, \{Daniel J.\} and Hong Sun and Shuqun Cheng and Weiwei Pan and Gert Storm and Khaled, \{Yazan S.\} and Michal Heger",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = may,

doi = "10.1016/j.jphotobiol.2024.112903",

language = "English",

volume = "254",

journal = "Journal of Photochemistry and Photobiology B: Biology",

issn = "1011-1344",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - Comparative analysis of whole cell-derived vesicular delivery systems for photodynamic therapy of extrahepatic cholangiocarcinoma

AU - on behalf of the Photodynamic Therapy Study Group

AU - Li, Mingjuan

AU - Bosman, Esmeralda D.C.

AU - Smith, Olivia M.

AU - Lintern, Nicole

AU - de Klerk, Daniel J.

AU - Sun, Hong

AU - Cheng, Shuqun

AU - Pan, Weiwei

AU - Storm, Gert

AU - Khaled, Yazan S.

AU - Heger, Michal

PY - 2024/5

Y1 - 2024/5

N2 - This first-in-its-class proof-of-concept study explored the use of bionanovesicles for the delivery of photosensitizer into cultured cholangiocarcinoma cells and subsequent treatment by photodynamic therapy (PDT). Two types of bionanovesicles were prepared: cellular vesicles (CVs) were fabricated by sonication-mediated nanosizing of cholangiocarcinoma (TFK-1) cells, whereas cell membrane vesicles (CMVs) were produced by TFK-1 cell and organelle membrane isolation and subsequent nanovesicularization by sonication. The bionanovesicles were loaded with zinc phthalocyanine (ZnPC). The CVs and CMVs were characterized (size, polydispersity index, zeta potential, stability, ZnPC encapsulation efficiency, spectral properties) and assayed for tumor (TFK-1) cell association and uptake (flow cytometry, confocal microscopy), intracellular ZnPC distribution (confocal microscopy), dark toxicity (MTS assay), and PDT efficacy (MTS assay). The mean ± SD diameter, polydispersity index, and zeta potential were 134 ± 1 nm, −16.1 ± 0.9, and 0.220 ± 0.013, respectively, for CVs and 172 ± 3 nm, −16.4 ± 1.1, and 0.167 ± 0.022, respectively, for CMVs. Cold storage for 1 wk and incorporation of ZnPC increased bionanovesicular diameter slightly but size remained within the recommended range for in vivo application (136–220 nm). ZnPC was incorporated into CVs and CMVs at an optimal photosensitizer:lipid molar ratio of 0.006 and 0.01, respectively. Both bionanovesicles were avidly taken up by TFK-1 cells, resulting in homogenous intracellular ZnPC dispersion. Photosensitization of TFK-1 cells did not cause dark toxicity, while illumination at 671 nm (35.3 J/cm2) produced LC50 values of 1.11 μM (CVs) and 0.51 μM (CMVs) at 24 h post-PDT, which is superior to most LC50 values generated in tumor cells photosensitized with liposomal ZnPC. In conclusion, CVs and CMVs constitute a potent photosensitizer platform with no inherent cytotoxicity and high PDT efficacy in vitro.

AB - This first-in-its-class proof-of-concept study explored the use of bionanovesicles for the delivery of photosensitizer into cultured cholangiocarcinoma cells and subsequent treatment by photodynamic therapy (PDT). Two types of bionanovesicles were prepared: cellular vesicles (CVs) were fabricated by sonication-mediated nanosizing of cholangiocarcinoma (TFK-1) cells, whereas cell membrane vesicles (CMVs) were produced by TFK-1 cell and organelle membrane isolation and subsequent nanovesicularization by sonication. The bionanovesicles were loaded with zinc phthalocyanine (ZnPC). The CVs and CMVs were characterized (size, polydispersity index, zeta potential, stability, ZnPC encapsulation efficiency, spectral properties) and assayed for tumor (TFK-1) cell association and uptake (flow cytometry, confocal microscopy), intracellular ZnPC distribution (confocal microscopy), dark toxicity (MTS assay), and PDT efficacy (MTS assay). The mean ± SD diameter, polydispersity index, and zeta potential were 134 ± 1 nm, −16.1 ± 0.9, and 0.220 ± 0.013, respectively, for CVs and 172 ± 3 nm, −16.4 ± 1.1, and 0.167 ± 0.022, respectively, for CMVs. Cold storage for 1 wk and incorporation of ZnPC increased bionanovesicular diameter slightly but size remained within the recommended range for in vivo application (136–220 nm). ZnPC was incorporated into CVs and CMVs at an optimal photosensitizer:lipid molar ratio of 0.006 and 0.01, respectively. Both bionanovesicles were avidly taken up by TFK-1 cells, resulting in homogenous intracellular ZnPC dispersion. Photosensitization of TFK-1 cells did not cause dark toxicity, while illumination at 671 nm (35.3 J/cm2) produced LC50 values of 1.11 μM (CVs) and 0.51 μM (CMVs) at 24 h post-PDT, which is superior to most LC50 values generated in tumor cells photosensitized with liposomal ZnPC. In conclusion, CVs and CMVs constitute a potent photosensitizer platform with no inherent cytotoxicity and high PDT efficacy in vitro.

KW - Anti-cancer treatment

KW - Biliary tumors

KW - Cell death

KW - Endocytosis

KW - Intracellular distribution

KW - Oxidative stress

KW - Photosensitized

KW - Reactive oxygen species

KW - Targeted photosensitizer delivery

KW - Vesicles

UR - https://www.scopus.com/pages/publications/85189912071

U2 - 10.1016/j.jphotobiol.2024.112903

DO - 10.1016/j.jphotobiol.2024.112903

M3 - Article

AN - SCOPUS:85189912071

SN - 1011-1344

VL - 254

JO - Journal of Photochemistry and Photobiology B: Biology

JF - Journal of Photochemistry and Photobiology B: Biology

M1 - 112903

ER -

Comparative analysis of whole cell-derived vesicular delivery systems for photodynamic therapy of extrahepatic cholangiocarcinoma

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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