Microneedle-assisted dual delivery of PUMA gene and celastrol for synergistic therapy of rheumatoid arthritis through restoring synovial homeostasis

Hua, Peng; Liang, Ruifeng; Yang, Suleixin; Tu, Yanbei; Chen, Meiwan

doi:10.1016/j.bioactmat.2024.02.030

Bioactive Materials

2024

DOI: 10.1016/j.bioactmat.2024.02.030

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Microneedle-assisted dual delivery of PUMA gene and celastrol for synergistic therapy of rheumatoid arthritis through restoring synovial homeostasis

Peng Hua,

Ruifeng Liang,

Suleixin Yang

et al.

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2024

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Cited by 3 publications

References 59 publications

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Human Serum Albumin‐Coated ¹⁰B Enriched Carbon Dots as Targeted “Pilot Light” for Boron Neutron Capture Therapy

Zhong,

Yang,

Pang

et al. 2024

Advanced Science

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Boron neutron capture therapy (BNCT) is a physiologically focused radiation therapy that relies on nuclear capture and fission processes. BNCT is regarded as one of the most promising treatments due to its excellent accuracy, short duration of therapy, and low side effects. The creation of novel boron medicines with high selectivity, ease of delivery, and high boron‐effective load is a current research topic. Herein, boron‐containing carbon dots (BCDs) and their human serum albumin (HSA) complexes (BCDs‐HSA) are designed and synthesized as boron‐containing drugs for BNCT. BCDs (10B: 7.1 wt%) and BCDs‐HSA exhibited excitation‐independent orange fluorescent emission which supported the use of fluorescence imaging for tracking 10B in vivo. The introduction of HSA enabled BCDs‐HSA to exhibit good biocompatibility and increased tumor accumulation. The active and passive targeting abilities of BCDs‐HSA are explored in detail. Subcutaneous RM‐1 tumors and B16‐F10 tumors both significantly decrease with BNCT, which consists of injecting BCDs‐HSA and then irradiating the area with neutrons. In short, this study provides a novel strategy for the delivery of boron and may broaden the perspectives for the design of boron‐containing carbon dots nanomedicine for BNCT.

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Human Serum Albumin‐Coated ¹⁰B Enriched Carbon Dots as Targeted “Pilot Light” for Boron Neutron Capture Therapy

Zhong,

Yang,

Pang

et al. 2024

Advanced Science

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Manipulation of protein corona for nanomedicines

Li,

Wang,

Zhou

2024

WIREs Nanomed Nanobiotechnol

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Nanomedicines have significantly advanced the development of diagnostic and therapeutic strategies for various diseases, while they still encounter numerous challenges. Upon entry into the human body, nanomedicines interact with biomolecules to form a layer of proteins, which is defined as the protein corona that influences the biological properties of nanomedicines. Traditional approaches have primarily focused on designing stealthy nanomedicines to evade biomolecule adsorption; however, due to the intricacies of the biological environment within body, this method cannot completely prevent biomolecule adsorption. As research on the protein corona progresses, manipulating the protein corona to modulate the in vivo behaviors of nanomedicines has become a research focus. In this review, modern strategies focused on influencing the biological efficacy of nanomedicines in vivo by manipulating protein corona, along with their wide‐ranging applications across diverse diseases are critically summarized, highlighted and discussed. Finally, future directions for this important yet challenging research area are also briefly discussed.This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures

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ML385, an Nrf2 Inhibitor, Synergically Enhanced Celastrol Triggered Endoplasmic Reticulum Stress in Lung Cancer Cells

Xu,

Chen,

Zhou

et al. 2024

ACS Omega

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Lung cancer is one of the leading causes of death. Celastrol is a natural product that has shown anticancer activity but has not yet been applied in clinical settings due to its narrow therapeutic window. In this study, we discovered that celastrol stimulates an abnormal rise in the reactive oxygen species (ROS) level in lung cancer cells and that the ROS scavenger N-acetylcysteine (NAC) could counteract the cell death caused by celastrol. At the same time, celastrol upregulated the expression of cytoprotective transcription factor Nrf2 and its downstream proteins, which are effective in preventing the oxidative damage caused by ROS accumulation. Notably, we found that the overexpression of Nrf2 enhances the tolerance of lung cancer cells to celastrol and that lung cancer cells H460 with a Keap1 mutation are insensitive to celastrol. This indicates that the increase in Nrf2 contributes to the survival of lung cancer cells. Thus, we brought in an Nrf2 inhibitor ML385 to suppress the activation of Nrf2. We found that when ML385 and celastrol were added together the survival rates of lung cancer cells decreased more and the detected ROS level became much higher compared to treatment with celastrol alone. We also discovered that ML385 suppressed the expression of HO-1 and GCLC, which amplified celastrol-induced ATF4/CHOP-dependent endoplasmic reticulum stress (ER stress). Above all, our study found that ML385 enhanced celastrol-induced increases in ROS and ER stress, leading to lung cancer cell death. This research provides a potential strategy for the preclinical investigation of celastrol.

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Microneedle-assisted dual delivery of PUMA gene and celastrol for synergistic therapy of rheumatoid arthritis through restoring synovial homeostasis

Cited by 3 publications

References 59 publications

Human Serum Albumin‐Coated ¹⁰B Enriched Carbon Dots as Targeted “Pilot Light” for Boron Neutron Capture Therapy

Human Serum Albumin‐Coated ¹⁰B Enriched Carbon Dots as Targeted “Pilot Light” for Boron Neutron Capture Therapy

Manipulation of protein corona for nanomedicines

ML385, an Nrf2 Inhibitor, Synergically Enhanced Celastrol Triggered Endoplasmic Reticulum Stress in Lung Cancer Cells

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Microneedle-assisted dual delivery of PUMA gene and celastrol for synergistic therapy of rheumatoid arthritis through restoring synovial homeostasis

Cited by 3 publications

References 59 publications

Human Serum Albumin‐Coated 10B Enriched Carbon Dots as Targeted “Pilot Light” for Boron Neutron Capture Therapy

Human Serum Albumin‐Coated 10B Enriched Carbon Dots as Targeted “Pilot Light” for Boron Neutron Capture Therapy

Manipulation of protein corona for nanomedicines

ML385, an Nrf2 Inhibitor, Synergically Enhanced Celastrol Triggered Endoplasmic Reticulum Stress in Lung Cancer Cells

Contact Info

Product

Resources

About

Human Serum Albumin‐Coated ¹⁰B Enriched Carbon Dots as Targeted “Pilot Light” for Boron Neutron Capture Therapy

Human Serum Albumin‐Coated ¹⁰B Enriched Carbon Dots as Targeted “Pilot Light” for Boron Neutron Capture Therapy