Dual-mode endogenous and exogenous sensitization of tumor radiotherapy through antifouling dendrimer-entrapped gold nanoparticles

Yang, Chao; Gao, Yue; Fan, Yu; Cao, Liu; Li, Jin; Ge, Yulong; Tu, Wenzhi; Liu, Yong; Cao, Xueyan; Shi, Xiangyang

doi:10.7150/thno.54930

Cited by 28 publications

(26 citation statements)

References 43 publications

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“…with enhanced photoelectric and Compton effects to exogenously increase the radiation response of cancer cells to RT 6 - 9 . Additionally, through endogenous modulation of the tumor hypoxia including normalization of tumor vessels 10 , 11 , intentional delivery of oxygen (O 2 ) 12 , knockdown of hypoxia-inducible factor-1α (HIF-1α) protein and downstream genes to relieve tumor invasion 13 , or catalytic decomposition of endogenous H 2 O 2 by catalase (CAT) 14 , tumor hypoxia can also be relieved for sensitized tumor RT. Though great progresses have been achieved, most of them only focus on a single process during RT (i.e., either by increasing the cellular radiosensitivity prior to ionizing radiation, enhancing the local radiation dose absorption during RT or inhibiting the DNA damage repair after RT), leading to limited radiosensitization efficacy for tumor therapy.…”

Section: Introductionmentioning

confidence: 99%

Intelligent design of polymer nanogels for full-process sensitized radiotherapy and dual-mode computed tomography/magnetic resonance imaging of tumors

Zhang

Chen

et al. 2022

Theranostics

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Rationale: Development of intelligent radiosensitization nanoplatforms for imaging-guided tumor radiotherapy (RT) remains challenging. We report here the construction of an intelligent nanoplatform based on poly( N -vinylcaprolactam) (PVCL) nanogels (NGs) co-loaded with gold (Au) and manganese dioxide (MnO 2 ) nanoparticles (NPs) for dual-mode computed tomography (CT)/magnetic resonance (MR) imaging-guided “full-process” sensitized RT of tumors. Methods: PVCL NGs were synthesized via precipitation polymerization and in situ loaded with Au and MnO 2 NPs. The created PVCL-Au-MnO 2 NGs were well characterized and systematically examined in their cytotoxicity, cellular uptake, intracellular oxygen and ·OH production, and cell cycle arrest in vitro , evaluated to disclose their RT sensitization effects of cancer cells and a tumor model, and assessed to validate their dual-mode CT/MR imaging potential, pharmacokinetics, biodistribution, and biosafety in vivo . Results: The formed PVCL-Au-MnO 2 NGs with a size of 121.5 nm and good stability can efficiently generate reactive oxygen species through a Fenton-like reaction to result in cell cycle distribution toward highly radiosensitive G2/M phase prior to X-ray irradiation, sensitize the RT of cancer cells under X-ray through the loaded Au NPs to induce the significant DNA damage, and further prevent DNA-repairing process after RT through the continuous production of O 2 catalyzed by MnO 2 in the hybrid NGs to relieve the tumor hypoxia. Likewise, the in vivo tumor RT can also be guided through dual mode CT/MR imaging due to the Au NPs and Mn(II) transformed from MnO 2 NPs. Conclusion: Our study suggests an intelligent PVCL-based theranostic NG platform that can achieve “full-process” sensitized tumor RT under the guidance of dual-mode CT/MR imaging.

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Section: Introductionmentioning

confidence: 99%

Intelligent design of polymer nanogels for full-process sensitized radiotherapy and dual-mode computed tomography/magnetic resonance imaging of tumors

Zhang

Chen

et al. 2022

Theranostics

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“…In another study, Yang et al proposed dendrimer-wrapped Au nanoparticles (Au DENPs) for delivering siRNA, which can achieve radiosensitization through enhanced X-ray absorption of high-Z elements and siRNA knockdown of HIF-1a protein as well as downstream genes. 118 The A549 cells treated with vector/si-HIF-1a showed lower cellular activity under 6 Gy X-ray irradiation, indicating the radiosensitization of the nanodrug delivery system. In addition, vector/si-HIF-1a + RT-treated tumor-bearing mice showed the smallest tumor size and no side effects, such as weight loss, which can safely and effectively inhibit tumor growth, indicating that endogenous and exogenous dual-mode nanoradiosensitizers were successfully prepared.…”

Section: Other Strategies For High-z Nanomedicine-based Multimodal Ra...mentioning

confidence: 94%

Multifunctional high-Z nanoradiosensitizers for multimodal synergistic cancer therapy

et al. 2022

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“…The nanosystem potently downregulated expression of HIF-1 alpha in vitro and in vivo and exhibited outstanding power to suppress cancer spreading in the orthotopic transplantation cancer model. The fifth-generation polyamidoamine dendritic polymers that were partially decorated by 1,3-propanesultone were employed for template fabrication of gold nanoparticles and obtained zwitterionic dendrimerentrapped gold nanoparticles were applied to deliver HIF-1 alpha siRNA (Yang C. et al, 2021). Decoration of amineterminated dendrimers with 1,3-propanesultone rendered the vector of antifouling property for enhanced serum transfection of HIF-1 alpha.…”

Section: Nanoformulations For Inhibiting Tumor Metastasismentioning

confidence: 99%

Nanodelivery Systems Delivering Hypoxia-Inducible Factor-1 Alpha Short Interfering RNA and Antisense Oligonucleotide for Cancer Treatment

Yan

Yao

et al. 2022

Front. Nanotechnol.

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Hypoxia-inducible factor (HIF), which plays a crucial role in oxygen homeostasis, contributes to immunosuppression, tumor angiogenesis, multidrug resistance, photodynamic therapy resistance, and metastasis. HIF as a therapeutic target has attracted scientists’ strong academic research interests. Short interfering RNA (siRNA) and antisense oligonucleotide (ASO) are the more promising and broadly utilized methods for oligonucleotide-based therapy. Their physicochemical characteristics such as hydrophilicity, negative charge, and high molecular weight make them impossible to cross the cell membrane. Moreover, siRNA and ASO are subjected to a rapid deterioration in circulation and cannot translocate into nuclear. Delivery of siRNA and ASO to specific gene targets should be realized without off-target gene silencing and affecting the healthy cells. Nanoparticles as vectors for delivery of siRNA and ASO possess great advantages and flourish in academic research. In this review, we summarized and analyzed regulation mechanisms of HIF under hypoxia, the significant role of HIF in promoting tumor progression, and recent academic research on nanoparticle-based delivery of HIF siRNA and ASO for cancer immunotherapy, antiangiogenesis, reversal of multidrug resistance and radioresistance, potentiating photodynamic therapy, inhibiting tumor metastasis and proliferation, and enhancing apoptosis are reviewed in this thesis. Furthermore, we hope to provide some rewarding suggestions and enlightenments for targeting HIF gene therapy.

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Dual-mode endogenous and exogenous sensitization of tumor radiotherapy through antifouling dendrimer-entrapped gold nanoparticles

Cited by 28 publications

References 43 publications

Intelligent design of polymer nanogels for full-process sensitized radiotherapy and dual-mode computed tomography/magnetic resonance imaging of tumors

Intelligent design of polymer nanogels for full-process sensitized radiotherapy and dual-mode computed tomography/magnetic resonance imaging of tumors

Multifunctional high-Z nanoradiosensitizers for multimodal synergistic cancer therapy

Nanodelivery Systems Delivering Hypoxia-Inducible Factor-1 Alpha Short Interfering RNA and Antisense Oligonucleotide for Cancer Treatment

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