Type I BODITh Photosensitizers with Twisted Conformation for Augmented Photodynamic Therapy and FOXO1-Involved Apoptosis

Tian Zhang; Jiahong Li; Jinjun Shao; Xiaorui Wang; Peng Chen; Huili Ma; Lulu Qu; Xiaochen Dong

doi:10.1021/acs.nanolett.5c01663

Type I BODITh Photosensitizers with Twisted Conformation for Augmented Photodynamic Therapy and FOXO1-Involved Apoptosis

Tian Zhang, Jiahong Li, Jinjun Shao^*, Xiaorui Wang, Peng Chen, Huili Ma^*, Lulu Qu, Xiaochen Dong^*

^*Corresponding author for this work

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

Abstract

Developing targeted type I photosensitizers with low oxygen-dependence is essential to overcome tumor hypoxia and address the short diffusion radius of free radicals in photodynamic therapy (PDT). Herein, two Boron dithiazolemethene (BODITh)-derivatives, SBDP-1 and SBDP-2 with different numbers of thiophene units, were designed as mitochondria-targeted type I photosensitizers with significant ·OH generation. Through theoretical calculations, the additional thiophene unit in SBDP-2 induced a torsional conformation with a smaller overlap integral of holes and electrons than SBDP-1, resulting in an increased spin-orbit coupling (SOC) constant with a decreased singlet-triplet energy gap (ΔE_ST), thereby promoting the intersystem crossing (ISC) process. Moreover, through a molecular docking study, SBDP-2 NPs could bind to miR-96 via hydrophobic interaction and trigger the forkhead box protein O1 (FOXO1) involved pathway to accelerate cell apoptosis. This work presented innovative type I photosensitizers with twisted conformation for efficient cancer PDT to conquer tumor hypoxia.

Original language	English
Journal	Nano Letters
DOIs	https://doi.org/10.1021/acs.nanolett.5c01663
Publication status	Accepted/In press - 2025
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2025 American Chemical Society.

ASJC Scopus Subject Areas

Bioengineering
General Chemistry
General Materials Science
Condensed Matter Physics
Mechanical Engineering

Keywords

photodynamic
photosensitizer
twisted conformation
type I

UN SDGs

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

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10.1021/acs.nanolett.5c01663

Cite this

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title = "Type I BODITh Photosensitizers with Twisted Conformation for Augmented Photodynamic Therapy and FOXO1-Involved Apoptosis",

abstract = "Developing targeted type I photosensitizers with low oxygen-dependence is essential to overcome tumor hypoxia and address the short diffusion radius of free radicals in photodynamic therapy (PDT). Herein, two Boron dithiazolemethene (BODITh)-derivatives, SBDP-1 and SBDP-2 with different numbers of thiophene units, were designed as mitochondria-targeted type I photosensitizers with significant ·OH generation. Through theoretical calculations, the additional thiophene unit in SBDP-2 induced a torsional conformation with a smaller overlap integral of holes and electrons than SBDP-1, resulting in an increased spin-orbit coupling (SOC) constant with a decreased singlet-triplet energy gap (ΔEST), thereby promoting the intersystem crossing (ISC) process. Moreover, through a molecular docking study, SBDP-2 NPs could bind to miR-96 via hydrophobic interaction and trigger the forkhead box protein O1 (FOXO1) involved pathway to accelerate cell apoptosis. This work presented innovative type I photosensitizers with twisted conformation for efficient cancer PDT to conquer tumor hypoxia.",

keywords = "photodynamic, photosensitizer, twisted conformation, type I",

author = "Tian Zhang and Jiahong Li and Jinjun Shao and Xiaorui Wang and Peng Chen and Huili Ma and Lulu Qu and Xiaochen Dong",

note = "Publisher Copyright: {\textcopyright} 2025 American Chemical Society.",

year = "2025",

doi = "10.1021/acs.nanolett.5c01663",

language = "English",

journal = "Nano Letters",

issn = "1530-6984",

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TY - JOUR

T1 - Type I BODITh Photosensitizers with Twisted Conformation for Augmented Photodynamic Therapy and FOXO1-Involved Apoptosis

AU - Zhang, Tian

AU - Li, Jiahong

AU - Shao, Jinjun

AU - Wang, Xiaorui

AU - Chen, Peng

AU - Ma, Huili

AU - Qu, Lulu

AU - Dong, Xiaochen

PY - 2025

Y1 - 2025

N2 - Developing targeted type I photosensitizers with low oxygen-dependence is essential to overcome tumor hypoxia and address the short diffusion radius of free radicals in photodynamic therapy (PDT). Herein, two Boron dithiazolemethene (BODITh)-derivatives, SBDP-1 and SBDP-2 with different numbers of thiophene units, were designed as mitochondria-targeted type I photosensitizers with significant ·OH generation. Through theoretical calculations, the additional thiophene unit in SBDP-2 induced a torsional conformation with a smaller overlap integral of holes and electrons than SBDP-1, resulting in an increased spin-orbit coupling (SOC) constant with a decreased singlet-triplet energy gap (ΔEST), thereby promoting the intersystem crossing (ISC) process. Moreover, through a molecular docking study, SBDP-2 NPs could bind to miR-96 via hydrophobic interaction and trigger the forkhead box protein O1 (FOXO1) involved pathway to accelerate cell apoptosis. This work presented innovative type I photosensitizers with twisted conformation for efficient cancer PDT to conquer tumor hypoxia.

AB - Developing targeted type I photosensitizers with low oxygen-dependence is essential to overcome tumor hypoxia and address the short diffusion radius of free radicals in photodynamic therapy (PDT). Herein, two Boron dithiazolemethene (BODITh)-derivatives, SBDP-1 and SBDP-2 with different numbers of thiophene units, were designed as mitochondria-targeted type I photosensitizers with significant ·OH generation. Through theoretical calculations, the additional thiophene unit in SBDP-2 induced a torsional conformation with a smaller overlap integral of holes and electrons than SBDP-1, resulting in an increased spin-orbit coupling (SOC) constant with a decreased singlet-triplet energy gap (ΔEST), thereby promoting the intersystem crossing (ISC) process. Moreover, through a molecular docking study, SBDP-2 NPs could bind to miR-96 via hydrophobic interaction and trigger the forkhead box protein O1 (FOXO1) involved pathway to accelerate cell apoptosis. This work presented innovative type I photosensitizers with twisted conformation for efficient cancer PDT to conquer tumor hypoxia.

KW - photodynamic

KW - photosensitizer

KW - twisted conformation

KW - type I

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U2 - 10.1021/acs.nanolett.5c01663

DO - 10.1021/acs.nanolett.5c01663

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SN - 1530-6984

JO - Nano Letters

JF - Nano Letters

ER -

Type I BODITh Photosensitizers with Twisted Conformation for Augmented Photodynamic Therapy and FOXO1-Involved Apoptosis

Abstract

Bibliographical note

ASJC Scopus Subject Areas

Keywords

UN SDGs

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