Photosensitizer Nanoparticles Boost Photodynamic Therapy for Pancreatic Cancer Treatment

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.

Photodynamic eradication of intratumoral microbiota with bacteria-targeted micelles overcomes gemcitabine resistance of pancreatic cancer

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.

手术导航用荧光探针

荧光成像技术因具有操作简便、分辨率高、安全性好且可实时成像等优势,在术中导航中具有广阔的应用前景。虽然目前还没有靶向荧光探针在临床上得到批准,但已经有相当一部分荧光探针进入了临床试验阶段。最早进入临床试验的是一些偶联肿瘤靶向配体的荧光染料,例如近红外菁染料(IRDye800CW)标记的肿瘤特异抗体,叶酸标记的异硫氰酸荧光素(EC17)等。近来,结构更复杂的荧光探针如酶反应激活型探针和PET/荧光双模态探针也逐步进入临床试验。本文依据近年来手术导航用荧光探针的最新研究进展,分别就受体介导的靶向荧光探针、可激活型靶向荧光探针、近红外二区(NIR-Ⅱ)荧光探针、多模态荧光探针和诊疗一体化探针进行了分类讨论,重点对正在进行临床研究及具有临床转化前景的荧光探针的分子设计原理进行了分析与总结,并对手术导航用荧光探针未来的发展进行了展望。

Spatial control of robust transgene expression in mouse artery endothelium under ultrasound guidance

Dear Editor,Dysfunctional vascular endothelial cells(ECs)contribute to the pathophysiology of several cardiovascular diseases,such as atherosclerosis and its life-threatening complications.1 Gene therapy can be a valuable approach to modulate endothelial cell function for the prevention of atherosclerosis.However,there is still a lack of method for transgene expression in vascular endothelium.2 Herein,an effective and specific strategy was established for noninvasive spatial control of transgene expression into the target region of the mouse artery without systemic spillover using an ultrasound and microbubble(MB)guided adenoassociated viral vector(UMGAAV)(Supplementary Fig.S1).To the best of our knowledge,this is the first report on noninvasive spatial control of transgene expression in arterial endothelium in vivo.

Current trends and key considerations in the clinical translation of targeted fluorescent probes for intraoperative navigation

The rapid development of fluorescence imaging for intraoperative navigation has spurred further development of targeted fluorescent probes in the past decade.Only a few nontargeted dyes,including indocyanine green and methylene blue,are currently applied for fluorescence guided surgery in the clinic.While no targeted fluorescent probes have been approved for the clinic,a number of them have entered clinical trials.These probes have emission wavelengths in the visible and near infrared(NIR)-I(700-900 nm)range.Among them,activatable probes and nanoprobes have generated special interest.Compared with NIR-I fluorescent probes,NIR-II(1000-1700 nm)fluorescent probes exhibit better intravital performance in terms of increased penetration depths,reduced tissue autofluorescence,and higher signalto-background ratios.However,more challenges are expected before the successful translation of NIR-II probes from bench to bedside.This review provides a brief overview of targeted fluorescent probes under clinical evaluation and recent achievements in the field of NIR-II fluorescence imaging.In addition,we outline key considerations concerning the design of fluorescent probes for clinical translation.