A tumour-selective cascade activatable self-detained system for drug delivery and cancer imaging

An, Hong Wei; Li, Li Li; Wang, Yi; Wang, Ziqi; Hou, Da‐Yong; Lin, Yao; Qiao, Sheng Lin; Wang, Man Di; Yang, Chao; Ye, Cong; Ma, Yang; Zhao, Xiao; Cai, Qian; Chen, Wen Ting; Lu, Chu Qi; Xu, Wanhai; Wang, Hao; Zhao, Yuliang

doi:10.1038/s41467-019-12848-5

Cited by 160 publications

(89 citation statements)

References 58 publications

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“…The reasons for increased interstitial fluid pressure probably involve blood-vessel leakiness, lymph-vessel abnormalities, interstitial fibrosis, and a contraction of the interstitial space mediated by stromal fibroblasts. High-molecular-weight compounds, such as, peptide assemblies, are transported in the interstitium mainly via convection rather than via diffusion (Heldin et al, 2004 ; An et al, 2019 ). Thus, a high interstitial fluid pressure induces a reduction of transcapillary transport and weakens the streaming of therapeutic drugs and delivery platforms from the circulation system through the interstitial space.…”

Section: Conclusion and Challengesmentioning

confidence: 99%

“…However, it is still a challenge to reduce the interstitial fluid pressure of tumors without affecting normal tissues (Heldin et al, 2004 ). In addition, drugs or drug-loaded supramolecules that self-assemble in situ and exhibit high retention efficiency in the specific tumor tissues also provide a promising solution for overcoming the high interstitial fluid pressure obstacle to adequate drug delivery (Gao et al, 2013 ; An et al, 2019 ), but these studies are still in the preliminary stage of exploration.…”

Section: Conclusion and Challengesmentioning

confidence: 99%

“…Currently, there are a diverse range of nanoscale carriers to meet different practical requirements, including inorganic nanoparticles (e.g., silica nanoparticles, quantum dots, gold nanoparticles, carbon-based, and magnetic iron oxide–based nanostructures), synthetic organic nanoparticles (e.g., polymer-based nanostructures and dendrimers), and bio-original nanomaterials (e.g., lipid-based nanoparticles, peptide assemblies, protein cages, exosomes, and DNA origami) (Li et al, 2017 ). Among these, peptide-based supramolecular nanostructures are an important type of carriers for drug delivery because of the following reasons: (i) the unique biochemical functionality encoded by peptide sequences enables an active targeting (i.e., peptides are targeted to receptors that are overexpressed on cancer cells) or cell membrane–penetrating processes (Wei et al, 2013 ; Kebebe et al, 2018 ); (ii) the structure of peptide assembly can be programmatically modulated by intrinsic or/and external stimuli to achieve a controllable release of the payload into the target region (Wei et al, 2013 ; Raza et al, 2019 ); (iii) peptides are biocompatible compared to the synthetic organic compounds; (iv) solid-phase synthesis benefits peptide synthesis with the simplicity of operation; (v) the reactive terminus or/and side chains of peptides can be used as a reactive site to conjugate chemotherapeutics (Wyatt et al, 2017 ; An et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Tumor Microenvironment–Responsive Peptide-Based Supramolecular Drug Delivery System

Zhang

et al. 2020

Front. Chem.

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Physical and biochemical differences between tumor tissues and normal tissues provide promising triggering factors that can be utilized to engineer stimuli-responsive drug delivery platforms for cancer treatment. Rationally designed peptide-based supramolecular architectures can perform structural conversion by responding to the tumor microenvironment and achieve the controlled release of antitumor drugs. This mini review summarizes recent approaches for designing internal trigger-responsive drug delivery platforms using peptide-based materials. Peptide assemblies that exhibit a stimuli-responsive structural conversion upon acidic pH, high temperature, high oxidative potential, and the overexpressed proteins in tumor tissues are emphatically introduced. We also discuss the challenges of current peptide-based supramolecular delivery platforms against cancer.

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Section: Conclusion and Challengesmentioning

confidence: 99%

Section: Conclusion and Challengesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tumor Microenvironment–Responsive Peptide-Based Supramolecular Drug Delivery System

Zhang

et al. 2020

Front. Chem.

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“…Activatable drug delivery system can release drug under specific environment, which can elevate the therapeutic efficacy and reduce side effect [ 101 ]. Meng et al designed a pH/GSH dual-stimuli-responsive nanogels for MRI-guided chemotherapy [ 74 ].…”

Section: Crosslinked Nanogels For Cancer Diagnosis and Imaging-guimentioning

confidence: 99%

Recent Advances in Crosslinked Nanogel for Multimodal Imaging and Cancer Therapy

Zhou

Yang

et al. 2020

Polymers

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Nanomaterials have been widely applied in the field of cancer imaging and therapy. However, conventional nanoparticles including micelles and liposomes may suffer the issue of dissociation in the circulation. In contrast, crosslinked nanogels the structures of which are covalently crosslinked have better physiological stability than micelles and liposomes, making them more suitable for cancer theranostics. In this review, we summarize recent advances in crosslinked nanogels for cancer imaging and therapy. The applications of nanogels in drug and gene delivery as well as development of novel cancer therapeutic methods are first introduced, followed by the introduction of applications in optical and multimodal imaging, and imaging-guided cancer therapy. The conclusion and future direction in this field are discussed at the end of this review.

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“…With technological advance and tool innovation, many resources and databases have empowered in depth studies on the mechanisms accounting for cancer treatment [5,6]. The drug-target investigation has been ongoing to discover novel therapeutics for pancreatic cancer [7,8]. However, whether these findings will translate to the clinical setting is not known.…”

Section: Introductionmentioning

confidence: 99%

The potential drug for treatment in pancreatic adenocarcinoma: a bioinformatical study based on distinct drug databases

et al. 2020

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Background: The prediction of drug-target interaction from chemical and biological data can advance our search for potential drug, contributing to a therapeutic strategy for pancreatic adenocarcinoma (PAAD). We aim to identify hub genes of PAAD and search for potential drugs from distinct databases. The docking simulation is adopted to validate our findings from computable perspective. Methods: Differently expressed genes (DEGs) of PAAD were performed based on TCGA. With two Cytoscape plugins of CentiScaPe and MCODE, hub genes were analyzed and visualized by STRING analysis of Protein-protein Interaction (PPI). The hub genes were further selected with significant prognostic values. In addition, we examined the correlation between hub genes and immune infiltration in PAAD. Subsequently, we searched for the hub gene-targeted drugs in Connectivity map (Cmap) and cBioportal, which provided a large body of candidate drugs. The hub gene, which was covered in the above two databases, was estimated in Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Herbal Ingredients' Targets (HIT) database, which collected natural herbs and related ingredients. After obtaining molecular structures, the potential ingredient from TCMSP was applied for a docking simulation. We finalized a network connectivity of ingredient and its targets. Results: A total of 2616 DEGs of PAAD were identified, then we further determined and visualized 24 hub genes by a connectivity analysis of PPI. Based on prognostic value, we identified 5 hub genes including AURKA (p = 0.0059), CCNA2 (p = 0.0047), CXCL10 (p = 0.0044), ADAM10 (p = 0.00043), and BUB1 (p = 0.0033). We then estimated tumor immune correlation of these 5 hub genes, because the immune effector process was one major result of GO analysis. Subsequently, we continued to search for candidate drugs from Cmap and cBioportal database. BUB1, not covered in the above two databases, was estimated in TCMSP and HIT databases. Our results revealed that genistein was a potential drug of BUB1. Next, we generated two docking modes to validate drug-target interaction based on their 3D structures. We eventually constructed a network connectivity of BUB1 and its targets. Conclusions: All 5 hub genes that predicted poor prognosis had their potential drugs, especially our findings showed that genistein was predicted to target BUB1 based on TCMSP and docking simulation. This study provided a reasonable approach to extensively retrieve and initially validate putative therapeutic agents for PAAD. In future, these drug-target results should be investigated with solid data from practical experiments.

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A tumour-selective cascade activatable self-detained system for drug delivery and cancer imaging

Cited by 160 publications

References 58 publications

Tumor Microenvironment–Responsive Peptide-Based Supramolecular Drug Delivery System

Tumor Microenvironment–Responsive Peptide-Based Supramolecular Drug Delivery System

Recent Advances in Crosslinked Nanogel for Multimodal Imaging and Cancer Therapy

The potential drug for treatment in pancreatic adenocarcinoma: a bioinformatical study based on distinct drug databases

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