Tumor microenvironment targeting with dual stimuli-responsive nanoparticles based on small heat shock proteins for antitumor drug delivery

Shi, Kaihong; Wang, Yu; Xu, Zhaoyi; Gui, Hongqin; Xu, Ningze; Wu, Shengyue; He, Congyuan; Zhao, Ziming

doi:10.1016/j.actbio.2020.07.031

Cited by 26 publications

(20 citation statements)

References 52 publications

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“… 387 In addition, some studies identified the TME‐targeting nanoparticles (NPs), HSP‐NPs, which based on a natural Methanococcus jannaschii small HSPs (Mj‐sHSPs), and showed the ability in improving therapeutic efficacy and decreasing chemotherapy adverse effect in tumor therapy. 388 …”

Section: Hspss As Potential Therapeutic Targetsmentioning

confidence: 99%

Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities

Yang

Zhou

et al. 2022

MedComm

267

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The heat shock proteins (HSPs) are ubiquitous and conserved protein families in both prokaryotic and eukaryotic organisms, and they maintain cellular proteostasis and protect cells from stresses. HSP protein families are classified based on their molecular weights, mainly including large HSPs, HSP90, HSP70, HSP60, HSP40, and small HSPs. They function as molecular chaperons in cells and work as an integrated network, participating in the folding of newly synthesized polypeptides, refolding metastable proteins, protein complex assembly, dissociating protein aggregate dissociation, and the degradation of misfolded proteins. In addition to their chaperone functions, they also play important roles in cell signaling transduction, cell cycle, and apoptosis regulation. Therefore, malfunction of HSPs is related with many diseases, including cancers, neurodegeneration, and other diseases. In this review, we describe the current understandings about the molecular mechanisms of the major HSP families including HSP90/HSP70/HSP60/HSP110 and small HSPs, how the HSPs keep the protein proteostasis and response to stresses, and we also discuss their roles in diseases and the recent exploration of HSP related therapy and diagnosis to modulate diseases. These research advances offer new prospects of HSPs as potential targets for therapeutic intervention.

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Section: Hspss As Potential Therapeutic Targetsmentioning

confidence: 99%

Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities

Yang

Zhou

et al. 2022

MedComm

267

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“…Physical approaches could be summarized as charge a conversion strategy, which relies on non-covalent adsorption of PEG to the nanoparticle surface [ 11 , 12 ]. In this way, the use of anionic natural polymers with charge properties, including polyglutamic acid and hyaluronic acid, gives assistance to the construction of a charge-reversal system [ 13 , 14 ]. Polyglutamic acid-based zwitterionic copolymers own abundant carboxylic moieties of glutamic chains to be interacted with cationic moieties [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Tumor Microenvironment-Responsive Shell/Core Composite Nanoparticles for Enhanced Stability and Antitumor Efficiency Based on a pH-Triggered Charge-Reversal Mechanism

et al. 2021

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High systemic stability and effective tumor accumulation of chemotherapeutic agents are indispensable elements that determine their antitumor efficacy. PEGylation of nanoparticles (NPs) could prolong the retention time in vivo by improving their stability in circulation, but treatment suffers reduced tumor penetration and cellular uptake of nanomedicines. The tumor microenvironment (TME)-responsive NPs maintain their stealth features during circulation and undergo a stimuli-responsive dePEGylation once exposed to the site of action, thereby achieving enhanced internalization in tumor cells. Herein, TME-responsive shell/core composite nanoparticles were prepared and optimized with enhanced stability and tumor intake efficiency. We synthesized 12-hydroxystearic acid-poly (ethylene glycol)-YGRKKRRQRRR (HA-PEG-TAT) as a post-insert apparatus in disulfiram (DSF)-encapsulated naked nanoparticles (N-NPs) in order to form a cationic core (TAT-NPs). Accordingly, the negatively charged poly (glutamate acid)-graft-poly (ethylene glycol) (PGlu-PEG) was further applied to the surface of TAT-NPs as a negative charged shell (PGlu-PEG/TAT-NPs) via the electrostatic interaction between glutamic acids and arginine at the outer ring of the TAT-NPs. PGlu-PEG/TAT-NPs displayed a huge loading capability for DSF with reduced degradation in plasma and exhibited rapid charge reversal when pH decreased from 7.4 to pH 6.5, demonstrating an excellent systemic stability as well as intelligent stimuli-responsive performance within the acidic TME. Furthermore, the in vivo antitumor study revealed that PGlu-PEG/TAT-NPs provided greater antitumor efficacy compared with free DSF and N-NPs with no obvious systemic toxicity. In conclusion, the TME-responsive shell/core composite NPs, consisting of PGlu-PEG and HS-PEG-TAT, could mediate an effective and biocompatible delivery of chemotherapeutic agents with clinical potential.

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“…A therapeutic response was obtained through the silencing of the signal transducer and activator of transcription 3 (STAT3) and of HIF-1α. This caused an increase of CD11b + cells and CD169 + M1 macrophages in the TME [165]. A second example are dual stimuli-responsive NPs.…”

Section: Strategies For Intervention With the Tmementioning

confidence: 99%

“…These have a multilayered structure: a protein cage with small heat shock proteins, a cationic layer, and a dual-sensitive coat. The release of the drug paclitaxel was possible only under conditions similar to the TME, e.g., acid pH and overexpressed hyaluronic acid [165]. A third example are nanoliposomes loaded with isoliquiritigenin to affect AMPK/mTOR mediated glycolysis in colorectal cancer [166].…”

Section: Strategies For Intervention With the Tmementioning

confidence: 99%

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

Schirrmacher¹

2020

Biomedicines

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Mitochondria are of great relevance to health, and their dysregulation is associated with major chronic diseases. Research on mitochondria—156 brand new publications from 2019 and 2020—have contributed to this review. Mitochondria have been fundamental for the evolution of complex organisms. As important and semi-autonomous organelles in cells, they can adapt their function to the needs of the respective organ. They can program their function to energy supply (e.g., to keep heart muscle cells going, life-long) or to metabolism (e.g., to support hepatocytes and liver function). The capacity of mitochondria to re-program between different options is important for all cell types that are capable of changing between a resting state and cell proliferation, such as stem cells and immune cells. Major chronic diseases are characterized by mitochondrial dysregulation. This will be exemplified by cardiovascular diseases, metabolic syndrome, neurodegenerative diseases, immune system disorders, and cancer. New strategies for intervention in chronic diseases will be presented. The tumor microenvironment can be considered a battlefield between cancer and immune defense, competing for energy supply and metabolism. Cancer cachexia is considered as a final stage of cancer progression. Nevertheless, the review will present an example of complete remission of cachexia via immune cell transfer. These findings should encourage studies along the lines of mitochondria, energy supply, and metabolism.

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Tumor microenvironment targeting with dual stimuli-responsive nanoparticles based on small heat shock proteins for antitumor drug delivery

Cited by 26 publications

References 52 publications

Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities

Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities

Tumor Microenvironment-Responsive Shell/Core Composite Nanoparticles for Enhanced Stability and Antitumor Efficiency Based on a pH-Triggered Charge-Reversal Mechanism

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

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