Sequential Rocket-Mode Bioactivating Ticagrelor Prodrug Nanoplatform Combining Light-Switchable Diphtherin Transgene System for Breast Cancer Metastasis Inhibition

The increased risk of breast cancer metastasis is closely linked to the effects of platelets. Our previously light-switchable diphtheria toxin A fragment (DTA) gene system, known as the LightOn system, has demonstrated significant therapeutic potential; it lacks antimetastatic capabilities. In this...

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Veröffentlicht in:ACS applied materials & interfaces 2023-11, Vol.15 (46), p.53198-53216
Hauptverfasser: Zou, Jiafeng, Sun, Rui, He, Muye, Chen, You, Cheng, Yi, Xia, Chuanhe, Ma, Ying, Zheng, Shulei, Fu, Xiuzhi, Yuan, Zeting, Lan, Minbo, Lou, Kaiyan, Chen, Xianjun, Gao, Feng
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container_end_page 53216
container_issue 46
container_start_page 53198
container_title ACS applied materials & interfaces
container_volume 15
creator Zou, Jiafeng
Sun, Rui
He, Muye
Chen, You
Cheng, Yi
Xia, Chuanhe
Ma, Ying
Zheng, Shulei
Fu, Xiuzhi
Yuan, Zeting
Lan, Minbo
Lou, Kaiyan
Chen, Xianjun
Gao, Feng
description The increased risk of breast cancer metastasis is closely linked to the effects of platelets. Our previously light-switchable diphtheria toxin A fragment (DTA) gene system, known as the LightOn system, has demonstrated significant therapeutic potential; it lacks antimetastatic capabilities. In this study, we devised an innovative system by combining cell membrane fusion liposomes (CML) loaded with the light-switchable transgene DTA (pDTA) and a ticagrelor (Tig) prodrug. This innovative system, named the sequential rocket-mode bioactivating drug delivery system (pDTA-Tig@CML), aims to achieve targeted pDTA delivery while concurrently inhibiting platelet activity through the sequential release of Tig triggered by reactive oxygen species with the tumor microenvironment. In vitro investigations have indicated that pDTA-Tig@CML, with its ability to sequentially release Tig and pDTA, effectively suppresses platelet activity, resulting in improved therapeutic outcomes and the mitigation of platelet driven metastasis in breast cancer. Furthermore, pDTA-Tig@CML exhibits enhanced tumor aggregation and successfully restrains tumor growth and metastasis. It also reduces the levels of ADP, ATP, TGF-β, and P-selectin both in vitro and in vivo, underscoring the advantages of combining the bioactivating Tig prodrug nanoplatform with the LightOn system. Consequently, pDTA-Tig@CML emerges as a promising light-switchable DTA transgene system, offering a novel bioactivating prodrug platform for breast cancer treatment.
doi_str_mv 10.1021/acsami.3c11594
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Our previously light-switchable diphtheria toxin A fragment (DTA) gene system, known as the LightOn system, has demonstrated significant therapeutic potential; it lacks antimetastatic capabilities. In this study, we devised an innovative system by combining cell membrane fusion liposomes (CML) loaded with the light-switchable transgene DTA (pDTA) and a ticagrelor (Tig) prodrug. This innovative system, named the sequential rocket-mode bioactivating drug delivery system (pDTA-Tig@CML), aims to achieve targeted pDTA delivery while concurrently inhibiting platelet activity through the sequential release of Tig triggered by reactive oxygen species with the tumor microenvironment. In vitro investigations have indicated that pDTA-Tig@CML, with its ability to sequentially release Tig and pDTA, effectively suppresses platelet activity, resulting in improved therapeutic outcomes and the mitigation of platelet driven metastasis in breast cancer. 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subjects Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Cell Line, Tumor
Female
Humans
Liposomes
Melanoma, Cutaneous Malignant
Prodrugs - pharmacology
Prodrugs - therapeutic use
Ticagrelor - pharmacology
Transgenes
Tumor Microenvironment
title Sequential Rocket-Mode Bioactivating Ticagrelor Prodrug Nanoplatform Combining Light-Switchable Diphtherin Transgene System for Breast Cancer Metastasis Inhibition
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