Single-dose in situ storage for intensifying anticancer efficacy via combinatorial strategy

Hou, Lin; Yan, Yingshan; Tian, Chunyu; Huang, Qian‐Xiao; Fu, Xiang-Jing; Zhang, Zhen; Zhang, Hongling; Zhang, Huijuan; Zhang, Zhenzhong

doi:10.1016/j.jconrel.2020.01.014

Cited by 13 publications

(4 citation statements)

References 36 publications

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“…Heat shock protein 70 (HSP70), a molecular chaperone that plays an important role in cell protection against various stress, is often overexpressed by cancer cells with PTT treatment. , It is also considered as a marker of immunogenic activation, for example, promoting the infiltration of DCs, macrophages, and effector T cells into the tumor, enhancing the secretion of T-helper type 1 (Th1) cytokines and boosting immunogenicity mediated by T cells . Hence, we detected the protein expression levels of HSP70 in 4T1 cells with different treatments by the immunofluorescence technique.…”

Section: Resultsmentioning

confidence: 99%

An Intelligent Biomimetic Nanoplatform for Holistic Treatment of Metastatic Triple-Negative Breast Cancer via Photothermal Ablation and Immune Remodeling

et al. 2020

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Metastasis is one of the main causes of failure in the treatment of triple-negative breast cancer (TNBC). Immunotherapy brings hope and opportunity to solve this challenge, while its clinical applications are greatly inhibited by the tumor immunosuppressive environment. Here, an intelligent biomimetic nanoplatform was designed based on dendritic large-pore mesoporous silica nanoparticles (DLMSNs) for suppressing metastatic TNBC by combining photothermal ablation and immune remodeling. Taking advantage of the ordered large-pore structure and easily chemically modified property of DLMSNs, the copper sulfide (CuS) nanoparticles with high photothermal conversion efficiency were in situ deposited inside the large pores of DLMSNs, and the immune adjuvant resiquimod (R848) was loaded controllably. A homogenous cancer cell membrane was coated on the surfaces of these DLMSNs, followed by conjugation with the anti-PD-1 peptide AUNP-12 through a polyethylene glycol linker with an acid-labile benzoic-imine bond. The thus-obtained AM@DLMSN@CuS/R848 was applied to holistically treat metastatic TNBC in vitro and in vivo. The data showed that AM@DLMSN@CuS/R848 had a high TNBC-targeting ability and induced efficient photothermal ablation on primary TNBC tumors under 980 nm laser irradiation. Tumor antigens thus generated and increasingly released R848 by response to the photothermal effect, combined with AUNP-12 detached from AM@DLMSN@CuS/R848 in the weakly acidic tumor microenvironment, synergistically exerted tumor vaccination, and T lymphocyte activation functions on immune remodeling to prevent TNBC recurrence and metastasis. Taken together, this study provides an intelligent biomimetic nanoplatform to enhance therapeutic outcomes in metastatic TNBC.

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Section: Resultsmentioning

confidence: 99%

An Intelligent Biomimetic Nanoplatform for Holistic Treatment of Metastatic Triple-Negative Breast Cancer via Photothermal Ablation and Immune Remodeling

et al. 2020

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“…It might be because low‐dose PTX can not only kill Tregs through Bcl‐2/Bax‐mediated apoptosis, but also reduce MDSCs in tumours and promote their differentiation into DCs. [ 35 , 36 , 37 ] Furthermore, inflammatory cytokines expression, such as IFN‐γ, interleukin‐6 (IL‐6), and TNF‐α were remarkably upregulated in ZnFe 2 O 4 ‐PTX@CCM group (Figure 7J–L ). Collectively, these results implied that ZnFe 2 O 4 ‐PTX@CCM could enhance the antitumor immune response and improve the immunosuppressive TME.…”

Section: Resultsmentioning

confidence: 99%

Programmed initiation and enhancement of cGAS/STING pathway for tumour immunotherapy via tailor‐designed ZnFe₂O₄‐based nanosystem

Yang,

He,

Zhang

et al. 2023

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The cyclic guanosine monophosphate‐adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signalling pathway has been a promising target for anticancer immunity, but rationally activating and enhancing this pathway in tumour cells is critical. Herein, a glutathione sensitive ZnFe2O4‐based nanosystem is developed to programmatically initiate and enhance the STING signalling pathway in tumour cells. The prepared ZnFe2O4 nanoparticles were coated with cancer cell membrane (CCM), which enabled the nanosystem target tumour cells. In tumour cells, ZnFe2O4 nanoparticles could be disintegrated by responding to high level glutathione, and the released Fe3+ generated reactive oxygen species to induce the DNA leakage into the cytoplasm to stimulate cGAS. Then Zn2+ promoted cGAS‐DNA phase separation to intensify the cGAS enzymatic activity. In addition, the low dose encapsulation of paclitaxel (PTX) acting as an antimitotic agent (ZnFe2O4‐PTX@CCM) ensured the sustained activation of cGAS/STING pathway. The in vitro and in vivo results confirmed that ZnFe2O4‐PTX@CCM elevated the cGAS/STING activity, promoted dendritic cell maturation, increased cytotoxic T lymphocyte and natural killer cells infiltration, eventually inhibiting the tumour progress and postoperative recurrence. This study provided feasible references on constructing STING activation nanosystem for tumour immunotherapy.

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“…In addition, hematological and biochemical analysis of the serum ( Fig. 6 B and C), such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (UREA), and creatinine (CREA) at the end of antitumor studies showed negligible damage on renal and hepatic functions 49 . These results demonstrate that DSF@HA/Cu-MOF NPs with great tumor inhibition potency possessed excellent biosafety in vivo .…”

Section: Resultsmentioning

confidence: 99%

In situ triggering antitumor efficacy of alcohol-abuse drug disulfiram through Cu-based metal-organic framework nanoparticles

Hou

Liu

et al. 2021

Acta Pharmaceutica Sinica B

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Although approved as an alcohol-abuse drug, disulfiram (DSF) exhibited potential anticancer activity when chelated with copper (Cu). However, the low level of intrinsic Cu, toxicity originated from exogenous Cu supplementation, and poor stability of DSF in vivo severely limited its application in cancer treatment. Herein, we proposed an in situ DSF antitumor efficacy triggered system, taking advantages of Cu-based metal-organic framework (MOF). In detail, DSF was encapsulated into Cu-MOF nanoparticles (NPs) during its formation, and the obtained NPs were coated with hyaluronic acid to enhance the tumor targetability and biocompatibility. Notably, DSF loaded Cu-MOF NPs maintained stability and integrity without Cu 2+ leakage in blood circulation, thus showing excellent biosafety. Once accumulating at tumor site, NPs were internalized into tumor cells via receptor-mediated endocytosis and released DSF and Cu 2+ simultaneously in the hyaluronidase-enriched and acidic intracellular tumor microenvironment. This profile lead to in situ chelation reaction between DSF and Cu 2+ , generating toxic DSF/Cu complex against tumor cells. Both in vitro and in vivo results demonstrated the programmed degradation and recombination property of Cu-based MOF NPs, which facilitated the tumor-specific chemotherapeutic effects of DSF. This system provided a promising strategy for the application of DSF in tumor therapy.

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Single-dose in situ storage for intensifying anticancer efficacy via combinatorial strategy

Cited by 13 publications

References 36 publications

An Intelligent Biomimetic Nanoplatform for Holistic Treatment of Metastatic Triple-Negative Breast Cancer via Photothermal Ablation and Immune Remodeling

An Intelligent Biomimetic Nanoplatform for Holistic Treatment of Metastatic Triple-Negative Breast Cancer via Photothermal Ablation and Immune Remodeling

Programmed initiation and enhancement of cGAS/STING pathway for tumour immunotherapy via tailor‐designed ZnFe₂O₄‐based nanosystem

In situ triggering antitumor efficacy of alcohol-abuse drug disulfiram through Cu-based metal-organic framework nanoparticles

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Single-dose in situ storage for intensifying anticancer efficacy via combinatorial strategy

Cited by 13 publications

References 36 publications

An Intelligent Biomimetic Nanoplatform for Holistic Treatment of Metastatic Triple-Negative Breast Cancer via Photothermal Ablation and Immune Remodeling

An Intelligent Biomimetic Nanoplatform for Holistic Treatment of Metastatic Triple-Negative Breast Cancer via Photothermal Ablation and Immune Remodeling

Programmed initiation and enhancement of cGAS/STING pathway for tumour immunotherapy via tailor‐designed ZnFe2O4‐based nanosystem

In situ triggering antitumor efficacy of alcohol-abuse drug disulfiram through Cu-based metal-organic framework nanoparticles

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Programmed initiation and enhancement of cGAS/STING pathway for tumour immunotherapy via tailor‐designed ZnFe₂O₄‐based nanosystem