Patients with pancreatic cancer(PCa)have a poor prognosis apart from the few suitable for surgery.Photodynamic therapy(PDT)is a minimally invasive treatment modality whose efficacy and safety in treating unresectable ...Patients with pancreatic cancer(PCa)have a poor prognosis apart from the few suitable for surgery.Photodynamic therapy(PDT)is a minimally invasive treatment modality whose efficacy and safety in treating unresectable localized PCa have been corroborated in clinic.Yet,it suffers from certain limitations during clinical exploitation,including insufficient photosensitizers(PSs)delivery,tumor-oxygenation dependency,and treatment escape of aggressive tumors.To overcome these obstacles,an increasing number of researchers are currently on a quest to develop photosensitizer nanoparticles(NPs)by the use of a variety of nanocarrier systems to improve cellular uptake and biodistribution of photosensitizers.Encapsulation of PSs with NPs endows them significantly higher accumulation within PCa tumors due to the increased solubility and stability in blood circulation.A number of approaches have been explored to produce NPs co-delivering multi-agents affording PDT-based synergistic therapies for improved response rates and durability of response after treatment.This review provides an overview of available data regarding the design,methodology,and oncological outcome of the innovative NPs-based PDT of PCa.展开更多
Increasing evidence suggests that intratumoral microbiota plays a pivotal role in tumor progression,immunosurveillance,metastasis,and chemosensitivity.Particularly,in pancreatic ductal adenocarcinoma,tumor-resident Ga...Increasing evidence suggests that intratumoral microbiota plays a pivotal role in tumor progression,immunosurveillance,metastasis,and chemosensitivity.Particularly,in pancreatic ductal adenocarcinoma,tumor-resident Gammaproteobacteria could transform the chemotherapeutic drug gemcitabine(Gem)into its inactive form,thus rendering chemotherapy ineffective.Herein,a strategy for selectively eradicating intratumoral bacteria was described for overcoming Gem resistance in a pancreatic cancer animal model.An antimicrobial peptide was linked with photosensitizer through a poly(ethylene glycol)chain,which can self-assemble into micelles with a diameter of∼20 nm.The micelles could efficiently kill bacteria under light irradiation by inducing membrane depolarization,thereby inhibiting Gem metabolism.In a bacteria-resident pancreatic cancer animal model,the selective photodynamic eradication of intratumoral bacteria was demonstrated to efficiently reverse Gem resistance.This research highlights antibacterial photodynamic therapy as a promising adjuvant strategy for cancer therapy by modulating intratumoral microbiota.展开更多
基金financially supported by Beijing Natural Science Foundation,Haidian,original innovation joint fund(No.17L20170)National Key Research and Development Program of China(No.2016YFA0201400)+3 种基金State Key Program of National Natural Science of China(No.81930047)Projects of International Cooperation and Exchanges NSFC-PSF(No.31961143003)National Project for Research and Development of Major Scientific Instruments(No.81727803)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(No.81421004).
文摘Patients with pancreatic cancer(PCa)have a poor prognosis apart from the few suitable for surgery.Photodynamic therapy(PDT)is a minimally invasive treatment modality whose efficacy and safety in treating unresectable localized PCa have been corroborated in clinic.Yet,it suffers from certain limitations during clinical exploitation,including insufficient photosensitizers(PSs)delivery,tumor-oxygenation dependency,and treatment escape of aggressive tumors.To overcome these obstacles,an increasing number of researchers are currently on a quest to develop photosensitizer nanoparticles(NPs)by the use of a variety of nanocarrier systems to improve cellular uptake and biodistribution of photosensitizers.Encapsulation of PSs with NPs endows them significantly higher accumulation within PCa tumors due to the increased solubility and stability in blood circulation.A number of approaches have been explored to produce NPs co-delivering multi-agents affording PDT-based synergistic therapies for improved response rates and durability of response after treatment.This review provides an overview of available data regarding the design,methodology,and oncological outcome of the innovative NPs-based PDT of PCa.
基金National Natural Science Foundation of China,Grant/Award Numbers:52273300,82102062,81930047China Postdoctoral Science Foundation,Grant/Award Number:2020TQ0008。
文摘Increasing evidence suggests that intratumoral microbiota plays a pivotal role in tumor progression,immunosurveillance,metastasis,and chemosensitivity.Particularly,in pancreatic ductal adenocarcinoma,tumor-resident Gammaproteobacteria could transform the chemotherapeutic drug gemcitabine(Gem)into its inactive form,thus rendering chemotherapy ineffective.Herein,a strategy for selectively eradicating intratumoral bacteria was described for overcoming Gem resistance in a pancreatic cancer animal model.An antimicrobial peptide was linked with photosensitizer through a poly(ethylene glycol)chain,which can self-assemble into micelles with a diameter of∼20 nm.The micelles could efficiently kill bacteria under light irradiation by inducing membrane depolarization,thereby inhibiting Gem metabolism.In a bacteria-resident pancreatic cancer animal model,the selective photodynamic eradication of intratumoral bacteria was demonstrated to efficiently reverse Gem resistance.This research highlights antibacterial photodynamic therapy as a promising adjuvant strategy for cancer therapy by modulating intratumoral microbiota.