Recent advances in type I organic photosensitizers for efficient photodynamic therapy for overcoming tumor hypoxia

Lu, Bingli; Wang, Lingyun; Tang, Hao; Cao, Duanlin

doi:10.1039/d3tb00545c

Cited by 31 publications

(15 citation statements)

References 152 publications

(212 reference statements)

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“…The 4T1 tumorbearing mice were used for in vivo fluorescence imaging and biodistribution study (n = 3). Free ICG or I@MSN-Im-PEG (10 mg/kg ICG per mouse) was intravenously injected into the mice followed by imaging with an in vivo imaging system (Bruker, FX Pro, USA) (E x /E m = 640/680 nm) at various time points (2,4,8,12,24,36, and 48 h). After imaging, the mice were executed, and the main organs (heart, liver, spleen, lung, and kidney) and tumors were collected for imaging ex vivo.…”

Section: 18mentioning

confidence: 99%

“…Hypoxia, a pervasive characteristic in solid tumors, could disrupt DNA damage repair pathways and suppress intratumor heterogeneity as well as immune responses, thereby facilitating tumor progression and metastasis. − Hypoxia arises from the imbalance between the heightened oxygen (O 2 ) demand triggered by rapid proliferation of tumor cells and the inadequate oxygen supply due to the aberrant and compromised tumor vascular system. − Enhancing the O 2 supply, which is achieved either by direct generation of O 2 at the tumor site or normalization of disordered tumor vasculature to enhance oxygen delivery, represents the primary strategy for alleviating tumor hypoxia . However, the transient alleviation of hypoxia fails to address the underlying issue of increased O 2 consumption resulting from the rapid proliferation of tumor cells .…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial-Targeting Nanotrapper Captured Copper Ions to Alleviate Tumor Hypoxia for Amplified Photoimmunotherapy in Breast Cancer

Huang,

Yu,

Sun

et al. 2024

ACS Appl. Mater. Interfaces

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Hypoxia is a pervasive feature of solid tumors, which significantly limits the therapeutic effect of photodynamic therapy (PDT) and further influences the immunotherapy efficiency in breast cancer. However, the transient alleviation of tumor hypoxia fails to address the underlying issue of increased oxygen consumption, resulting from the rapid proliferation of tumor cells. At present, studies have found that the reduction of the oxygen consumption rate (OCR) by cytochrome C oxidase (COX) inhibition that induced oxidative phosphorylation (OXHPOS) suppression was able to solve the proposed problem. Herein, we developed a specific mitochondrial-targeting nanotrapper (I@ MSN-Im-PEG), which exhibited good copper chelating ability to inhibit COX for reducing the OCR. The results proved that the nanotrapper significantly alleviated the hypoxic tumor microenvironment by copper chelation in mitochondria and enhanced the PDT effect in vitro and in vivo. Meanwhile, the nanotrapper improved photoimmunotherapy through both enhancing PDT-induced immunogenetic cell death (ICD) effects and reversing Tregmediated immune suppression on 4T1 tumor-bearing mice. The mitochondrial-targeting nanotrapper provided a novel and efficacious strategy to enhance the PDT effect and amplify photoimmunotherapy in breast cancer.

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Section: 18mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitochondrial-Targeting Nanotrapper Captured Copper Ions to Alleviate Tumor Hypoxia for Amplified Photoimmunotherapy in Breast Cancer

Huang,

Yu,

Sun

et al. 2024

ACS Appl. Mater. Interfaces

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“…Photodynamic therapy is a less invasive therapy that selectively kills cells at the site of irradiation [1,2]. In this therapy, a photosensitizer converts intracellular oxygen to singlet oxygen ( 1 O 2 ) in response to light, and then 1 O 2 induces death in surrounding cells [3,4].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Nanoparticulation Method and Cell-Killing Effect following the Mitochondrial Delivery of Hydrophobic Porphyrin-Based Photosensitizers

Naganawa,

Zhao,

Takano

et al. 2024

IJMS

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Photodynamic therapy is expected to be a less invasive treatment, and strategies for targeting mitochondria, the main sources of singlet oxygen, are attracting attention to increase the efficacy of photodynamic therapy and reduce its side effects. To date, we have succeeded in encapsulating the photosensitizer rTPA into MITO-Porter (MP), a mitochondria-targeted Drug Delivery System (DDS), aimed at mitochondrial delivery of the photosensitizer while maintaining its activity. In this study, we report the results of our studies to alleviate rTPA aggregation in an effort to improve drug efficacy and assess the usefulness of modifying the rTPA side chain to improve the mitochondrial retention of MITO-Porter, which exhibits high therapeutic efficacy. Conventional rTPA with anionic side chains and two rTPA analogs with side chains that were converted to neutral or cationic side chains were encapsulated into MITO-Porter. Low-MP (MITO-Porter with Low Drug/Lipid) exhibited high drug efficacy for all three types of rTPA, and in Low-MP, charged rTPA-encapsulated MP exhibited high drug efficacy. The cellular uptake and mitochondrial translocation capacities were similar for all particles, suggesting that differences in aggregation rates during the incorporation of rTPA into MITO-Porter resulted in differences in drug efficacy.

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“…Recent studies suggested that type I PSs with free radicals such as O 2 •– and OH • radical generation are more promising in hypoxia solid tumor treatment over conventional type II photosensitizers with 1 O 2 generation. ,, Therefore, the types of ROS generated from these nanoparticles were further evaluated. SOSG was selected for 1 O 2 detection.…”

mentioning

confidence: 99%

Achieving beyond 100% Triplet State Generation with Singlet Fission Strategy for High-Performance Photosensitizer Design

Liu,

Li,

Gong

et al. 2024

ACS Materials Lett.

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As the key of photodynamic therapy (PDT), the current photosensitizer (PS) design highly relies on promoting the intersystem crossing (ISC) process to form the triplet excited state, thus generating toxic reactive oxygen species (ROS). However, ISC is a spin-forbidden process with a low triplet state generation yield (<100%). Herein, as a proof of concept, we report a new strategy of aggregation induced singlet fission (SF) process with an ultrafast rate (<100 ps) and a very high triplet yield (>100%) to design efficient PSs. Such a unique SF strategy is demonstrated with an anthracene derivative of BPA-An, which shows Jaggregation enhanced ROS generation ability. Mechanism studies with aggregation behavior and fs-transient absorption spectroscopy indicate that BPA-An in Jaggregate state can efficiently generate triplet state via the SF process with a 158% triplet yield and thus possesses excellent Type-I and Type-II ROS generation ability in nanoparticle (NP) format. Both cellular and animal experiments further prove the excellent PDT antitumor performance of BPA-An NPs. To the best of our knowledge, this work shall represent the first example of utilizing SF as the design rule to promote the triplet state generation of PSs, which shall pave a new avenue in PDT.

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Recent advances in type I organic photosensitizers for efficient photodynamic therapy for overcoming tumor hypoxia

Abstract: Photodynamic therapy (PDT) with oxygen-dependent character is a noninvasive therapeutic method for cancer treatment. However, its clinical therapeutic effect is greatly restricted by tumor hypoxia. What’s more, both PDT-mediated oxygen...

Cited by 31 publications

References 152 publications

Mitochondrial-Targeting Nanotrapper Captured Copper Ions to Alleviate Tumor Hypoxia for Amplified Photoimmunotherapy in Breast Cancer

Mitochondrial-Targeting Nanotrapper Captured Copper Ions to Alleviate Tumor Hypoxia for Amplified Photoimmunotherapy in Breast Cancer

Investigation of the Nanoparticulation Method and Cell-Killing Effect following the Mitochondrial Delivery of Hydrophobic Porphyrin-Based Photosensitizers

Achieving beyond 100% Triplet State Generation with Singlet Fission Strategy for High-Performance Photosensitizer Design

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