Tumor microenvironment-responsive artesunate loaded Z-scheme heterostructures for synergistic photo-chemodynamic therapy of hypoxic tumor

Lü, Jie; Wang, Xiaoyu; Zhang, Xue; Xu, Runpei; Hu, S.; Wang, Shuangling; Li, Meng

doi:10.1016/j.ajps.2023.100798

Cited by 2 publications

(1 citation statement)

References 48 publications

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“…Two crucial issues should be considered for improving the PDT effectiveness of cancer. First, oxygen plays a significant role in the production of ROSs during PDT [ 7 – 11 ]. However, aggressive proliferation of solid cancer and the twisted vascular system lead to liquefaction necrosis [ 12 ], resulting in a partial pressure of oxygen below 5 mmHg [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy

Li,

Wang,

Tao

et al. 2024

Bioinorganic Chemistry and Applications

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Photodynamic therapy (PDT) has received increasing attention for tumor therapy due to its minimal invasiveness and spatiotemporal selectivity. However, the poor targeting of photosensitizer and hypoxia of the tumor microenvironment limit the PDT efficacy. Herein, eccentric hollow mesoporous organic silica nanoparticles (EHMONs) are prepared by anisotropic encapsulation and hydrothermal etching for constructing PDT nanoplatforms with targeting and hypoxia-alleviating properties. The prepared EHMONs possess a unique eccentric hollow structure, a uniform size (300 nm), a large cavity, and ordered mesoporous channels (2.3 nm). The EHMONs are modified with the mitochondria-targeting molecule triphenylphosphine (CTPP) and photosensitizers chlorin e6 (Ce6). Oxygen-carrying compound perfluorocarbons (PFCs) are further loaded in the internal cavity of EHMONs. Hemolytic assays and in vitro toxicity experiments show that the EHMONs-Ce6-CTPP possesses very good biocompatibility and can target mitochondria of triple-negative breast cancer, thus increasing the accumulation of photosensitizers Ce6 at mitochondria after entering cancer cells. The EHMONs-Ce6-CTPP@PFCs with oxygen-carrying ability can alleviate hypoxia after entering in the cancer cell. Phantom and cellular experiments show that the EHMONs-Ce6-CTPP@PFCs produce more singlet oxygen reactive oxygen species (ROSs). Thus, in vitro and in vivo experiments demonstrated that the EHMONs-Ce6-CTPP@PFCs showed excellent treatment effects for triple-negative breast cancer. This research provides a new method for a targeting and oxygen-carrying nanoplatform for enhancing PDF effectiveness.

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Section: Introductionmentioning

confidence: 99%

Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy

Li,

Wang,

Tao

et al. 2024

Bioinorganic Chemistry and Applications

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Quintuple Free‐Radical Therapy: An Ultralong‐Retention FAND for NIR‐Involved Multiple Site‐Acting Hypoxic Tumor Therapy

Zhang,

Zhao,

Fang

et al. 2024

Adv Funct Materials

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The heavy dependence on intratumoral O2 and H2O2 availability has greatly restricted ROS‐based therapy. Although O2/H2O2‐irrelevant free‐radical nanogenerator has garnered tremendous attention as a promising anticancer candidate to overcome the above intrinsic limitations of ROS‐based treatment, the practical therapeutic efficacy of free‐radical therapy is still hindered by limited free‐radical type and inferior tumor retention performance. Herein, inspired by the new concept of full‐API nanodrug (FAND) with 100% active pharmaceutical ingredient (API) content and repurposing of clinical anti‐malaria drug artesunate (ARTE) as an anticancer free‐radical generator, the AFeI FANDs composed of ARTE, human essential Fe3+, and FDA‐approved fluorescent agent ICG for hypoxic tumor therapy are rationally designed and constructed. Attractively, the completely pharmaceutically active components ARTE, Fe3+, and ICG can be responsively liberated in the acidic tumor microenvironment and synergistically produce five types of free radicals including •O2−, •C, •OH, LOO•, and 1O2, leading to robust mitochondrial injury, nuclear DNA damage, and lipid peroxides. More importantly, the AFeI FANDs displayed ultralong tumor retention longer than 108 h and favorable tumor suppression outcomes under mild NIR irradiation. Collectively, the presented first paradigm of FAND‐based quintuple free‐radical therapy expands new horizons for the development of clinically transferable nanomedicine for tumor therapy.

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Tumor microenvironment-responsive artesunate loaded Z-scheme heterostructures for synergistic photo-chemodynamic therapy of hypoxic tumor

Cited by 2 publications

References 48 publications

Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy

Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy

Quintuple Free‐Radical Therapy: An Ultralong‐Retention FAND for NIR‐Involved Multiple Site‐Acting Hypoxic Tumor Therapy

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