Hypoxia-alleviated nanoplatform to enhance chemosensitivity and sonodynamic effect in pancreatic cancer

Chen, Jifan; Bao, Yuheng; Song, Yue; Zhang, Cong; Qiu, Fuqiang; Sun, Yu; Xin, Lei; Cao, Jing; Jiang, Yifan; Luo, Jiali; Zhang, Chao; Wang, Guowei; Qun-yin, LI; Liu, Yajing; Tong, Weijun; Huang, Pintong

doi:10.1016/j.canlet.2021.07.008

Cited by 24 publications

(19 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 23a,b ] Compared to other cancers, PDAC exhibits a rather high degree of radioresistance due to the hypoxic features caused by hypervascularity and dense matrix. [ 7a,b,24 ] This could be partially addressed by combining PDAC RT with some clinically implemented radio‐sensitizing agents with cell cycle arrest activity, [ 25 ] such as gemcitabine, capecitabine, or 5‐FU. [ 23b,25b ] One prospective clinical evaluation of the FOLFIRINOX regimen followed by individualized RT shows a high rate of R0 resection and prolonged survival, [ 26 ] indicating the potential advantage of chemoradiotherapy (CRT) in PDAC treatment.…”

Section: Introductionmentioning

confidence: 99%

Deep‐Penetrating Triple‐Responsive Prodrug Nanosensitizer Actuates Efficient Chemoradiotherapy in Pancreatic Ductal Adenocarcinoma Models

Tang

et al. 2022

Small

View full text Add to dashboard Cite

Chemoradiotherapy (CRT) is the most accepted treatment for locally advanced pancreatic ductal adenocarcinoma (PDAC) and can significantly improve the R0 resection rate. However, there are few long‐term survivors after CRT. Although some polymer nanoparticles have shown potential in alleviating the dose‐limiting toxicity and assisting the chemotherapy of PDAC, there are few efficient nanosensitizers (NS) available for CRT of this malignancy, especially in the context of its hypoxic nature. Herein, based on the biological features of PDAC, a γ‐glutamyl transpeptidase (GGT)/glutathione (GSH)/hypoxia triple‐responsive prodrug NS to overcome the biological barrier and microenvironmental limitations confronted by CRT in PDAC is developed. Due to triple‐responsiveness, deep tumor penetration, GSH/hypoxia‐responsive drug release/activation, and hypoxia‐induced chemoradio‐sensitization can be simultaneously achieved with this NS. As a result, tumor shrinkage after CRT with this NS can be observed in both subcutaneous and orthotopic PDAC models, foreshadowing its potential in clinical neoadjuvant CRT.

show abstract

Section: Introductionmentioning

confidence: 99%

Deep‐Penetrating Triple‐Responsive Prodrug Nanosensitizer Actuates Efficient Chemoradiotherapy in Pancreatic Ductal Adenocarcinoma Models

Tang

et al. 2022

Small

View full text Add to dashboard Cite

show abstract

“…The prolongation of the duty cycle was associated with decreased CV staining and decreased bacterial viability in the XTT assay (Figure S2a,d), with similar changes being observed for the increases in power (Figure S2b,e) and frequency (Figure S2c,f), consistent with enhanced biofilm clearance. To further confirm the NP-induced disruption of the biofilm barrier and the associated bacterial killing, the biofilms were cultured in confocal dishes and subjected to PBS, US, MEM, MN+US, MPN+US, or TPMN+US treatment, with US performed using optimal therapeutic settings (1.5 W/cm 2 , 50% duty cycle, 1 MHz). − After treatment, these biofilms were stained with CV (Figure a) and analyzed by the XTT assay (Figure b). Relative to the control group and other experimental groups, TMPN treatment was associated with highly efficient dissociation of the integrity of the biofilm and bacterial killing.…”

Section: Resultsmentioning

confidence: 99%

Ultrasound-Activatable Phase-Shift Nanoparticle as a Targeting Antibacterial Agent for Efficient Eradication ofPseudomonas aeruginosaBiofilms

Xin

Zhang

Chen

et al. 2022

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Biofilms are physical barriers composed of extracellular polymeric substances (EPS) that enable planktonic bacteria to resist host responses and antibacterial treatments, complicating efforts to clear bacteria such as Pseudomonas aeruginosa (P. aeruginosa) and thereby contributing to persistently chronic infections. As such, it is critical to develop a robust antimicrobial strategy capable of effectively eradicating P. aeruginosa biofilms and to further address aggressive clinical infection. In this study, ultrasound-activatable targeted nanoparticles were designed by using poly(lactic-co-glycolic acid) (PLGA) nanoparticles to encapsulate phase-transformable perfluoropentane (PFP) and the antibiotic meropenem via a double emulsion approach, followed by conjugation with anti-P. aeruginosa antibodies. In this strategy, ultrasound exposure can trigger PFP to produce microbubbles, inducing ultrasonic cavitation effects that can disrupt EPS components and allow nanoparticles to release meropenem to kill P. aeruginosa directly and accelerate the associated wound healing. These nanoparticles eradicated biofilms effectively and cleared bacteria in vitro as well as exhibited potent anti-infective activity in vivo. In summary, this study demonstrates the efficacy of a sonobactericidal strategy as a means of effectively and reliably eliminating biofilms.

show abstract

“…To date, by using SDT, some encouraging achievements have been obtained on various tumor issues like breast and pancreatic tumor at the laboratory level. [ 9 , 10 , 11 ] However, further application of SDT remains severely restricted by its limited anticancer efficacy, even with the most advanced sonosensitizers, including both traditional organic molecules (such as phenothiazine compounds and fluoroquinolone antibiotics) and inorganic nanomaterials (such as noble metal nanoparticles and transition metal oxide). [ 12 , 13 , 14 , 15 , 16 ] Therefore, the development of effective sonosensitizers with improved SDT performance is the key for its further clinical transformation.…”

Section: Introductionmentioning

confidence: 99%

Ultrathin‐FeOOH‐Coated MnO₂ Sonosensitizers with Boosted Reactive Oxygen Species Yield and Remodeled Tumor Microenvironment for Efficient Cancer Therapy

et al. 2022

View full text Add to dashboard Cite

Sonodynamic therapy (SDT) typically suffers from compromised anticancer efficacy owing to the low reactive oxygen species (ROS) yield and complicated tumor microenvironment (TME) which can consume ROS and support the occurrence and development of tumors. Herein, ultrathin‐FeOOH‐coated MnO2 nanospheres (denoted as MO@FHO) as sonosensitizers which can not only facilitate ultrasound (US)‐triggered ROS but also tune the TME by hypoxia alleviation, H2O2 consumption as well as glutathione (GSH) depletion are designed. The FeOOH coating will boost the production yield of singlet oxygen (1O2) and hydroxyl radicals (•OH) by inhibiting the recombination of US‐initiated electron–hole pairs and Fenton‐like reaction, respectively. Additionally, the catalase‐like and GSH peroxidase‐like activities of MO@FHO nanospheres enable them to break the TME equilibrium via hypoxia alleviation and GSH depletion. The combination of high ROS yield and fundamental destruction of TME equilibrium results in satisfactory antitumor outcomes, as demonstrated by the high tumor suppression efficacy of MO@FHO on MDA‐MB‐231‐tumor‐bearing mice. No obvious toxicity is detected to normal tissues at therapeutic doses in vivo. The capability to modulate the ROS production and TME simultaneously can afford new probability for the development of advanced sonosensitizers for synergistic comprehensive cancer therapy.

show abstract

Hypoxia-alleviated nanoplatform to enhance chemosensitivity and sonodynamic effect in pancreatic cancer

Cited by 24 publications

References 35 publications

Deep‐Penetrating Triple‐Responsive Prodrug Nanosensitizer Actuates Efficient Chemoradiotherapy in Pancreatic Ductal Adenocarcinoma Models

Deep‐Penetrating Triple‐Responsive Prodrug Nanosensitizer Actuates Efficient Chemoradiotherapy in Pancreatic Ductal Adenocarcinoma Models

Ultrasound-Activatable Phase-Shift Nanoparticle as a Targeting Antibacterial Agent for Efficient Eradication ofPseudomonas aeruginosaBiofilms

Ultrathin‐FeOOH‐Coated MnO₂ Sonosensitizers with Boosted Reactive Oxygen Species Yield and Remodeled Tumor Microenvironment for Efficient Cancer Therapy

Contact Info

Product

Resources

About

Hypoxia-alleviated nanoplatform to enhance chemosensitivity and sonodynamic effect in pancreatic cancer

Cited by 24 publications

References 35 publications

Deep‐Penetrating Triple‐Responsive Prodrug Nanosensitizer Actuates Efficient Chemoradiotherapy in Pancreatic Ductal Adenocarcinoma Models

Deep‐Penetrating Triple‐Responsive Prodrug Nanosensitizer Actuates Efficient Chemoradiotherapy in Pancreatic Ductal Adenocarcinoma Models

Ultrasound-Activatable Phase-Shift Nanoparticle as a Targeting Antibacterial Agent for Efficient Eradication ofPseudomonas aeruginosaBiofilms

Ultrathin‐FeOOH‐Coated MnO2 Sonosensitizers with Boosted Reactive Oxygen Species Yield and Remodeled Tumor Microenvironment for Efficient Cancer Therapy

Contact Info

Product

Resources

About

Ultrathin‐FeOOH‐Coated MnO₂ Sonosensitizers with Boosted Reactive Oxygen Species Yield and Remodeled Tumor Microenvironment for Efficient Cancer Therapy