scholarly journals Gelatinase-sensitive nanoparticles loaded with photosensitizer and STAT3 inhibitor for cancer photothermal therapy and immunotherapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lin-Lin Bu ◽  
Han-Qi Wang ◽  
Yuanwei Pan ◽  
Lei Chen ◽  
Hao Wu ◽  
...  

AbstractMatrix metalloproteinase (MMP) 2 and 9 are the family members of proteases normally up-regulated in tumor to enhance the invasion and metastatic of tumor cells, and are associated with poor outcome of head and neck squamous cell carcinomas (HNSCCs). In the present work, MMPs-degradable gelatin nanoparticles (GNPs) are simultaneously loaded with photosensitizer indocyanine green (ICG) along with signal transducer activator of transcription 3 (STAT3) inhibitor NSC74859 (NSC, N) for efficient photothermal therapy (PTT) and immunotherapy of HNSCCs. In the tumor tissue, Gel-N-ICG nanoparticle was degraded and encapsulated ICG and NSC were effectively released. Under near-infrared (NIR) irradiation, the released ICG nanoparticles enabled effective photothermal destruction of tumors, and the STAT3 inhibitor NSC elicited potent antitumor immunity for enhanced cancer therapy. Based on two HNSCC mouse models, we demonstrated that Gel-N-ICG significantly delayed tumor growth without any appreciable body weight loss. Taken together, the strategy reported here may contribute that the stimuli-responsive proteases triggered nanoplatform could reduce tumor size more effectively in complex tumor microenvironment (TME) through combination of PTT and immunotherapy. Graphical Abstract

2021 ◽  
Author(s):  
Lin-Lin Bu ◽  
Han-Qi Wang ◽  
Yuan-Wei Pan ◽  
Lei Chen ◽  
Hao Wu ◽  
...  

Abstract Matrix metalloproteinases (MMP) 2 and 9 are the family members of proteases normally up-regulated in tumor to enhance the metastatic of tumor cells, and have been associated with poor outcome of head and neck squamous cell carcinomas (HNSCCs). In the present work, MMPs-degradable gelatin nanoparticles (GNPs) are simultaneously loaded with photosensitizer indocyanine green (ICG) along with signal transducer activator of transcription 3 (STAT3) inhibitor NSC74859 (NSC, N) for efficient photothermal therapy (PTT) and immunotherapy of HNSCCs. In the tumor tissue, Gel-N-ICG was degraded and encapsulated ICG and NSC were effectively released. Under near-infrared (NIR) irradiation, the released ICG nanoparticles enabled effective photothermal destruction of tumors, and the STAT3 inhibitor NSC elicited potent antitumor immunity for enhanced cancer therapy. Based on two HNSCC mouse models, we demonstrated that Gel-N-ICG significantly delayed tumor growth without any appreciable body weight loss. Taken together, the strategy reported here may contribute that the proteases-trigger platform could reduce tumor size more effectively in complex tumor microenvironment (TME) through combination of PTT and immunotherapy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoxia Song ◽  
Zhi Chen ◽  
Xue Zhang ◽  
Junfeng Xiong ◽  
Teng Jiang ◽  
...  

AbstractMagnetic micro/nanorobots attracted much attention in biomedical fields because of their precise movement, manipulation, and targeting abilities. However, there is a lack of research on intelligent micro/nanorobots with stimuli-responsive drug delivery mechanisms for cancer therapy. To address this issue, we developed a type of strong covalently bound tri-bead drug delivery microrobots with NIR photothermal response azobenzene molecules attached to their carboxylic surface groups. The tri-bead microrobots are magnetic and showed good cytocompatibility even when their concentration is up to 200 µg/mL. In vitro photothermal experiments demonstrated fast NIR-responsive photothermal property; the microrobots were heated to 50 °C in 4 min, which triggered a significant increase in drug release. Motion control of the microrobots inside a microchannel demonstrated the feasibility of targeted therapy on tumor cells. Finally, experiments with lung cancer cells demonstrated the effectiveness of targeted chemo-photothermal therapy and were validated by cell viability assays. These results indicated that tri-bead microrobots have excellent potential for targeted chemo-photothermal therapy for lung cancer cell treatment.


Materials ◽  
2019 ◽  
Vol 12 (5) ◽  
pp. 779 ◽  
Author(s):  
Austin Doughty ◽  
Ashley Hoover ◽  
Elivia Layton ◽  
Cynthia Murray ◽  
Eric Howard ◽  
...  

As a result of their unique compositions and properties, nanomaterials have recently seen a tremendous increase in use for novel cancer therapies. By taking advantage of the optical absorption of near-infrared light, researchers have utilized nanostructures such as carbon nanotubes, gold nanorods, and graphene oxide sheets to enhance photothermal therapies and target the effect on the tumor tissue. However, new uses for nanomaterials in targeted cancer therapy are coming to light, and the efficacy of photothermal therapy has increased dramatically. In this work, we review some of the current applications of nanomaterials to enhance photothermal therapy, specifically as photothermal absorbers, drug delivery vehicles, photoimmunological agents, and theranostic tools.


2012 ◽  
Vol 72 (12) ◽  
pp. 2990-2999 ◽  
Author(s):  
Shoichi Ihara ◽  
Hiroshi Kida ◽  
Hisashi Arase ◽  
Lokesh P. Tripathi ◽  
Yi-An Chen ◽  
...  

2017 ◽  
Author(s):  
I Silva ◽  
V Rausch ◽  
T Peccerella ◽  
G Millonig ◽  
HK Seitz ◽  
...  

2019 ◽  
Vol 19 (10) ◽  
pp. 817-827
Author(s):  
Jianbo Zhu ◽  
Lijuan Deng ◽  
Baozhen Chen ◽  
Wenqing Huang ◽  
Xiandong Lin ◽  
...  

Background:Recurrence is the leading cause of treatment failure and death in patients with gastric cancer (GC). However, the mechanism underlying GC recurrence remains unclear, and prognostic markers are still lacking.Methods:We analyzed DNA methylation profiles in gastric cancer cases with shorter survival (<1 year) or longer survival (> 3 years), and identified candidate genes associated with GC recurrence. Then, the biological effects of these genes on gastric cancer were studied.Results:A novel gene, magnesium-dependent phosphatase 1 (mdp1), was identified as a candidate gene whose DNA methylation was higher in GC samples from patients with shorter survival and lower in patients with longer survival. MDP1 protein was highly expressed in GC tissues with longer survival time, and also had a tendency to be expressed in highly differentiated GC samples. Forced expression of MDP1 in GC cell line BGC-823 inhibited cell proliferation, whereas the knockdown of MDP1 protein promoted cell growth. Overexpression of MDP1 in BGC-823 cells also enhanced cell senescence and apoptosis. Cytoplasmic kinase protein c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (Stat3) were found to mediate the biological function of MDP1.Conclusion:These results suggest that MDP1 protein suppresses the survival of gastric cancer cells and loss of MDP expression may benefit the recurrence of gastric cancer.


Nanoscale ◽  
2021 ◽  
Author(s):  
Jinsong Xiong ◽  
Qinghuan Bian ◽  
Shuijin Lei ◽  
Yatian Deng ◽  
Kehan Zhao ◽  
...  

Near-infrared (NIR) light induced photothermal cancer therapy using nanomaterials as photothermal agents has attracted considerable research interest over the past few years. As the key factor in the photothermal therapy...


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