Theranostics最新文献

{"title":"Subarachnoid hemorrhage distinctively disrupts the glymphatic and meningeal lymphatic systems in beagles.","authors":"Jiaqi Wang, Tao Lv, Feng Jia, Yang Li, Weiwei Ma, Zhi-Peng Xiao, Weifeng Yu, Heng Zhao, Xiaohua Zhang, Qin Hu","doi":"10.7150/thno.100982","DOIUrl":"https://doi.org/10.7150/thno.100982","url":null,"abstract":"<p><p>Subarachnoid hemorrhage (SAH) induced acute impairment of the glymphatic system, but few have investigated the dysfunction of the meningeal lymphatic system and their contribution to the pathophysiology of SAH. In addition, most studies were conducted in rodent animals. We aimed to investigate the impact of SAH on glymphatic and meningeal lymphatic function in a large animal model using beagles and to evaluate the effects of intermittent cistern magna CSF drainage on these systems. <b>Methods:</b> The SAH model was created in beagles via endovascular perforation using a digital subtraction angiography machine. Intermittent cistern magna CSF drain was performed daily from 1 d to 3 d after SAH. We examined CSF pressure, neuronal death, enlargement of perivascular space (PVS), hydrocephalus, and neurological and cognitive deficits before and after SAH. The dynamics of glymphatic and meningeal lymphatic functions were analyzed by quantifying the signal intensity of dimeglumine gadopentetate (Gd-DTPA) using T1-weighted magnetic resonance imaging (MRI). Measurements were taken before SAH and at 1 h, 1 week, and 2 weeks post-SAH. <b>Results:</b> SAH in beagles caused significant blood clots, neuronal death, increased CSF pressure, hydrocephalus, and neurological and cognitive deficits. MRI revealed dilated ventricles and enlarged PVS post-SAH. The glymphatic system's function, assessed by Gd-DTPA distribution, showed reduced CSF influx and glymphatic impairment after SAH, particularly in the ipsilateral hemisphere, persisting for a week with partial recovery at 2 weeks. For lymphatic clearance, Gd-DTPA rapidly filled the olfactory bulbs, optic nerves, facial and vestibulocochlear nerves, and spinal nerves under normal conditions. SAH caused delayed and reduced Gd-DTPA efflux outflow in these areas, disrupting lymphatic clearance. Despite initial dysfunction, increased hemoglobin levels in cervical lymph nodes indicated active blood clearance post-SAH, with recovery by 2 weeks. Treatment with intermittent cistern magna CSF drain significantly ameliorated the glymphatic and meningeal lymphatic dysfunction after SAH. <b>Conclusion:</b> SAH impaired both glymphatic and meningeal lymphatic functions in beagles, with better restoration of lymphatic function post-SAH, which may contribute to functional recovery after SAH. External CSF drain is an effective therapeutic approach to facilitate the recovery of glymphatic and meningeal lymphatic function following SAH.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p-STAT3-elevated E3 ubiquitin ligase DTX4 confers the stability of HBV cccDNA by ubiquitinating APOBEC3B in liver.","authors":"Lina Zhao, Hongfeng Yuan, Yufei Wang, Chunyu Hou, Pan Lv, Huihui Zhang, Guang Yang, Xiaodong Zhang","doi":"10.7150/thno.99407","DOIUrl":"https://doi.org/10.7150/thno.99407","url":null,"abstract":"<p><p><b>Background:</b> Clinically, the persistence of HBV cccDNA is the major obstacle in anti-HBV therapy. However, the underlying mechanism of HBV cccDNA is poorly understood. The transcriptional factor STAT3 is able to activate HBV replication in liver. <b>Approach & Results:</b> RNA-Seq analysis demonstrated that cucurbitacin I targeting STAT3 was associated with virus replication in liver. HBV-infected human liver chimeric mouse model and HBV hydrodynamic injection mouse model were established. Then, we validated that cucurbitacin I effectively limited the stability of HBV cccDNA and HBV replication in cells, in which cucurbitacin I enhanced the sensitivity of pegylated interferon α (PEG-IFN α) against HBV <i>via</i> combination <i>in vitro</i> and <i>in vivo</i>. Mechanistically, we identified that cucurbitacin I increased the levels of APOBEC3B to control HBV cccDNA by inhibiting p-STAT3 in cells, resulting in the inhibition of HBV replication. Moreover, RNA-Seq data showed that E3 ubiquitin ligase DTX4 might be involved in the events. Then, we observed that HBV particles could upregulate DTX4 by increasing the levels of p-STAT3 <i>in vitro</i> and <i>in vivo</i>. The p-STAT3-elevated DTX4/male-specific lethal 2 (MSL2) independently and synergistically enhanced the stability of HBV cccDNA by facilitating the ubiquitination degradation of APOBEC3B in cells, leading to the HBV replication. <b>Conclusions:</b> p-STAT3-elevated DTX4 confers the stability of HBV cccDNA and HBV replication by facilitating the ubiquitination degradation of APOBEC3B. Cucurbitacin Ⅰ effectively enhances the sensitivity of PEG-IFN α in anti-HBV therapy by inhibiting the p-STAT3/DTX4/MSL2/APOBEC3B signalling. Our finding provides new insights into the mechanism of HBV cccDNA. The p-STAT3 and DTX4/MSL2 might serve as the therapeutical targets of HBV cccDNA.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctionally disordered TiO₂ nanoneedles prevent periprosthetic infection and enhance osteointegration by killing bacteria and modulating the osteoimmune microenvironment.","authors":"Yangmengfan Chen, Liqiang Zhou, Ming Guan, Shue Jin, Peng Tan, Xiaoxue Fu, Zongke Zhou","doi":"10.7150/thno.98219","DOIUrl":"https://doi.org/10.7150/thno.98219","url":null,"abstract":"<p><p><b>Rationale:</b> Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are effective interventions for end-stage osteoarthritis; however, periprosthetic infection is a devastating complication of arthroplasty. To safely prevent periprosthetic infection and enhance osteointegration, the surface modification strategy was utilized to kill bacteria, modulate the osteoimmune microenvironment, and improve new bone formation. <b>Methods:</b> We used the hydrothermal method to fabricate a bionic insect wing with the disordered titanium dioxide nanoneedle (TNN) coating. The mussel-inspired poly-dopamine (PDA) and antibacterial silver nanoparticles (AgNPs) were coated on TNN, named AgNPs-PDA@TNN, to improve the biocompatibility and long-lasting bactericidal capacity. The physicochemical properties of the engineered specimen were evaluated with SEM, AFM, XPS spectrum, and water contact assay. The biocompatibility, bactericidal ability, and the effects on macrophages and osteogenic differentiation were assessed with RT-qPCR, Western blotting, live/dead staining, immunofluorescent staining, <i>etc</i>. <b>Results:</b> The AgNPs-PDA@TNN were biocompatible with macrophages and exhibited immunomodulatory ability to promote M2 macrophage polarization. In addition, AgNPs-PDA@TNN ameliorated the cytotoxicity caused by AgNPs, promoted cell spreading, and increased osteogenesis and matrix deposition of BMSCs. Furthermore, AgNPs-PDA@TNN exhibited bactericidal ability against <i>E. coli</i> and <i>S. aureus</i> by the bionic nanostructure and coated AgNPs. Various imaging analyses indicated the enhanced bactericidal ability and improved new bone formation by AgNPs-PDA@TNN <i>in vivo</i>. H&E, Gram, and Masson staining, verified the improved bone formation, less inflammation, infection, and fibrosis encapsulation. The immunofluorescence staining confirmed the immunomodulatory ability of AgNPs-PDA@TNN <i>in vivo</i>. <b>Conclusion:</b> The bionic insect wing AgNPs-PDA@TNN coating exhibited bactericidal property, immunomodulatory ability, and enhanced osteointegration. Thus, this multidimensional bionic implant surface holds promise as a novel strategy to prevent periprosthetic infection.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotinamide mononucleotide enhances fracture healing by promoting skeletal stem cell proliferation.","authors":"Yitian Shi, Jiayin Peng, Mengfan Liu, Xiling Qi, Siyu Li, Qiangqiang Li, Qing Jiang, Liming Zheng, Jiankun Xu, Yun Zhao, Yifeng Zhang","doi":"10.7150/thno.98149","DOIUrl":"https://doi.org/10.7150/thno.98149","url":null,"abstract":"<p><p>The process of skeletal regeneration initiated by stem cells following injury, especially in fractures, is significantly impaired by aging and adverse factors. Nicotinamide mononucleotide (NMN), a critical endogenous precursor of nicotinamide adenine dinucleotide (NAD), has garnered extensive attention for its multifaceted regulatory functions in living organisms and its wide-ranging therapeutic potential. However, whether NMN contributes to trauma-induced skeletal regeneration remains unclear. <b>Methods</b>: The transverse femoral shaft fracture model was employed to evaluate the potential advantages of NMN administration for overall repair during the initial fracture stages in male mice through micro-CT analysis, histochemistry, and biomechanical testing. The pro-proliferative function of NMN on skeletal stem cells (SSCs) was investigated through flow cytometry, qRT-PCR, NAD content measurement, and cell proliferation assay. <b>Results</b>: In this study, we observed that the administration of NMN during the initial phase of fracture in mice led to a larger callus and corresponding improvement in micro-CT parameters. NMN enhances the cartilaginous component of the callus by elevating the NAD content, consequently accelerating subsequent endochondral ossification and the fracture healing process. Subsequent analyses elucidated that NMN was beneficial in promoting the expansion of diverse stem cells <i>in vivo</i> and <i>in vitro</i> potentially via modulation of the Notch signaling pathway. Moreover, the depletion of macrophages profoundly obstructs the proliferation of SSCs. <b>Conclusion</b>: Our discoveries provide a potential strategy for enhancing fracture healing through stimulation of callus SSC proliferation at an early stage, shedding light on the translational value of NMN as an enhancer for skeletal regeneration and highlighting the pivotal role of macrophage-stem cell interactions in governing the regenerative influence of NMN on stem cells.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A hierarchically acidity-unlocking nanoSTING stimulant enables cascaded STING activation for potent innate and adaptive antitumor immunity.","authors":"Shunyao Zhu, Tao He, Yan Wang, Yushan Ma, Wenmei Li, Songlin Gong, Yanghui Zhu, Xiangwei Wang, Xu Xu, Qinjie Wu, Changyang Gong, Yanjie You","doi":"10.7150/thno.98272","DOIUrl":"https://doi.org/10.7150/thno.98272","url":null,"abstract":"<p><p><b>Rationale:</b> Neoadjuvant chemotherapy (NAC) has been recognized as an indispensable strategy for advanced malignancies. Nevertheless, the enhancement of overall patient survival in NAC recipients has encountered challenges due to the limited sustainability of its efficacy and the inability to prevent postoperative tumor recurrence and metastasis. <b>Methods:</b> We devise a hierarchically unlocking nanoSTING stimulant liposome (AUG) as a neoadjuvant chemoimmunotherapy agent in the debulking of tumors prior to surgery and prevention of postoperative tumor recurrence and metastasis by simultaneously activating innate and adaptive antitumor immune responses. In the weakly acidic tumor microenvironment, the hydrazone bond within AUG is initially cleaved, leading to the release of a cyclic seven-membered ring containing tertiary amine that serve to activate the stimulator of interferon genes (STING) pathway. Following this, AUG undergoes degradation within lysosomes, facilitating the release of doxorubicin and ultimately inducing immunogenic cell death along with leakage of double-stranded DNA into the cytoplasm. <b>Results:</b> The hierarchically acidity-unlocking pattern enables cascaded STING activation, achieving over 90% tumor growth inhibition in subcutaneous xenograft model and preventing 75% of mice from postsurgical metastasis or recurrence when combined with immune checkpoint inhibitors. <b>Conclusion:</b> Our strategy highlights the potency of AUG as a neoadjuvant paradigm for presurgical tumor debulking and as a preventive measure against postoperative tumor recurrence and metastasis.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxanthine is a metabolic biomarker for inducing GSDME-dependent pyroptosis of endothelial cells during ischemic stroke.","authors":"Jing Ye, Xinyuan Bi, Shiyu Deng, Xianghui Wang, Ze Liu, Qian Suo, Jiao Wu, Haoran Chen, Yong Wang, Kun Qian, Rubing Shi, Jing Zhao, Guo-Yuan Yang, Jian Ye, Yaohui Tang","doi":"10.7150/thno.100090","DOIUrl":"https://doi.org/10.7150/thno.100090","url":null,"abstract":"<p><p><b>Rationale:</b> Stroke induces metabolic changes in the body, and metabolites have become potential biomarkers for stroke. However, the specific metabolites involved in stroke and the mechanisms underlying brain injury during stroke remain unclear. <b>Methods:</b> Surface-enhanced Raman spectroscopy (SERS) and liquid chromatography-mass spectrometry (LC‒MS) analysis of clinical serum samples from 69 controls and 51 ischemic stroke patients who underwent reperfusion within 24 hours were performed to identify differentially abundant metabolites. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) and then intravenously injected with hypoxanthine. The infarct area was evaluated via tetrazolium chloride (TTC) staining, and behavior tests were conducted. Blood-brain barrier (BBB) leakage was assessed by Evans blue and IgG staining. Human blood vessel organoids were used to investigate the mechanism of hypoxanthine-induced pyroptosis of endothelial cells. <b>Results:</b> SERS and LC‒MS revealed the metabolic profiles of serum from stroke patients and controls with high sensitivity, speed and accuracy. Hypoxanthine levels were significantly elevated in the acute stage of ischemic stroke in both patients and mice (p < 0.001 after Bonferroni correction). In addition, increasing hypoxanthine increased the infarct area and aggravated BBB leakage and neurobehavioral deficits in mice after ischemic stroke. Further mechanistic studies using endothelial cells, human blood vessel organoids, and stroke mice demonstrated that hypoxanthine-mediated gasdermin E (GSDME)-dependent pyroptosis of endothelial cells occurs through intracellular Ca²⁺ overload. <b>Conclusion:</b> Our study identified hypoxanthine as an important metabolite that induces vascular injury and BBB disruption in stroke through triggering GSDME-dependent pyroptosis of endothelial cells.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: A thermosensitive, reactive oxygen species-responsive, MR409-encapsulated hydrogel ameliorates disc degeneration in rats by inhibiting the secretory autophagy pathway: Erratum.","authors":"Qiangqiang Zheng, Haotian Shen, Zongrui Tong, Linxiang Cheng, Yuzi Xu, Zhiyun Feng, Shiyao Liao, Xiaojian Hu, Zongyou Pan, Zhengwei Mao, Yue Wang","doi":"10.7150/thno.103020","DOIUrl":"https://doi.org/10.7150/thno.103020","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.7150/thno.47723.].</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noninvasive closed-loop acoustic brain-computer interface for seizure control.","authors":"Junjie Zou, Houminji Chen, Xiaoyan Chen, Zhengrong Lin, Qihang Yang, Changjun Tie, Hong Wang, Lili Niu, Yanwu Guo, Hairong Zheng","doi":"10.7150/thno.99820","DOIUrl":"https://doi.org/10.7150/thno.99820","url":null,"abstract":"<p><p><b>Rationale:</b> The brain-computer interface (BCI) is core tasks in comprehensively understanding the brain, and is one of the most significant challenges in neuroscience. The development of novel non-invasive neuromodulation technique will drive major innovations and breakthroughs in the field of BCI. <b>Methods:</b> We develop a new noninvasive closed-loop acoustic brain-computer interface (aBCI) for decoding the seizure onset based on the electroencephalography and triggering ultrasound stimulation of the vagus nerve to terminate seizures. Firstly, we create the aBCI system and decode the onset of seizure via a multi-level threshold model based on the analysis of wireless-collected electroencephalogram (EEG) signals recorded from above the hippocampus. Then, the different acoustic parameters induced acoustic radiation force were used to stimulate the vagus nerve in a rat model of epilepsy-induced by pentylenetetrazole. Finally, the results of epileptic EEG signal triggering ultrasound stimulation of the vagus nerve to control seizures. In addition, the mechanism of aBCI control seizures were investigated by real-time quantitative polymerase chain reaction (RT-qPCR). <b>Results:</b> In a rat model of epilepsy, the aBCI system selectively actives mechanosensitive neurons in the nodose ganglion while suppressing neuronal excitability in the hippocampus and amygdala, and stops seizures rapidly upon ultrasound stimulation of the vagus nerve. Physical transection or chemical blockade of the vagus nerve pathway abolish the antiepileptic effects of aBCI. In addition, aBCI shows significant antiepileptic effects compared to conventional vagus nerve electrical stimulation in an acute experiment. <b>Conclusions:</b> Closed-loop aBCI provides a novel, safe and effective tool for on-demand stimulation to treat abnormal neuronal discharges, opening the door to next generation non-invasive BCI.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing photothermal therapy of tumors with image-guided thermal control of gene-expressing bacteria.","authors":"Fengyi Zeng, Meng Du, Yaozhang Yang, Jinghui Fang, Yuanyuan Wang, MeeiChyn Goh, Yan Lin, Huaiyu Wang, Fei Yan, Zhiyi Chen","doi":"10.7150/thno.98257","DOIUrl":"https://doi.org/10.7150/thno.98257","url":null,"abstract":"<p><p><b>Purpose:</b> Bacteria-mediated tumor therapy has showed promising potential for cancer therapy. However, the efficacy of bacterial monotherapy treatment which can express and release therapeutic proteins in tumors has been found to be unsatisfactory. To date, synergistic therapy has emerged as a promising approach to achieve stronger therapeutic outcomes compared to bacterial monotherapy. It is a challenge to visualize these tumor-homing bacteria <i>in vivo</i> and guide them to express and release in situ therapeutic proteins. <b>Procedure:</b> We have developed a kind of engineered bacteria (named CGB@ICG) genetically incorporating acoustic reporter proteins and thermo-inducible ClyA expression gene circuit and chemically modified with indocyanine green on the bacterial surface. The presence of acoustic reporter proteins and indocyanine green facilitates the visualization of CGB@ICG via contrast-enhanced ultrasound imaging and optical imaging, making it possible to guide the sound wave or laser to irradiate precisely these bacteria for inducing the expression of ClyA protein via acoustic- or photothermal effects. The expression and secretion of ClyA protein in the tumor, combined with photothermal therapy, greatly enhanced the anti-tumor efficacy of the engineered bacteria and improved their biosafety. <b>Results:</b> We successfully performed multimodal imaging of CGB@ICG <i>in vivo</i> resulting in remoting control the expression of ClyA protein in tumor. <i>In vivo</i> experiments showed that bacteria-mediated therapy combined photothermal therapy exhibited a rapid decrease in tumor volume compared to other groups, while the tumor volume of the combination therapy group continued to decrease and even achieved complete healing. Thus, combination therapy not only reduced the rate of tumor growth but also prevented the proliferation of tumor cells for an extended period. <b>Conclusion:</b> Our study demonstrated that CGB@ICG serves as an efficacious imaging agent and delivery vector to combine engineered bacteria with photothermal therapy, holding great promise for tumor treatment.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collagen type I PET/MRI enables evaluation of treatment response in pancreatic cancer in pre-clinical and first-in-human translational studies.","authors":"Shadi A Esfahani, Hua Ma, Shriya Krishna, Sergey Shuvaev, Mark Sabbagh, Caitlin Deffler, Nicholas Rotile, Jonah Weigand-Whittier, Iris Y Zhou, Ciprian Catana, Onofrio A Catalano, David T Ting, Pedram Heidari, Eric Abston, Michael Lanuti, Genevieve M Boland, Priyanka Pathak, Hannah Roberts, Kenneth K Tanabe, Motaz Qadan, Carlos Fernandez-Del Castillo, Angela Shih, Aparna R Parikh, Colin D Weekes, Theodore S Hong, Peter Caravan","doi":"10.7150/thno.100116","DOIUrl":"https://doi.org/10.7150/thno.100116","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is an invasive and rapidly progressive malignancy. A major challenge in patient management is the lack of a reliable imaging tool to monitor tumor response to treatment. Tumor-associated fibrosis characterized by high type I collagen is a hallmark of PDAC, and fibrosis further increases in response to neoadjuvant chemoradiotherapy (CRT). We hypothesized that molecular positron emission tomography (PET) using a type I collagen-specific imaging probe, ⁶⁸Ga-CBP8 can detect and measure changes in tumor fibrosis in response to standard treatment in mouse models and patients with PDAC. <b>Methods:</b> We evaluated the specificity of ⁶⁸Ga-CBP8 PET to tumor collagen and its ability to differentiate responders from non-responders based on the dynamic changes of fibrosis in nude mouse models of human PDAC including FOLFIRNOX-sensitive (PANC-1 and PDAC6) and FOLFIRINOX-resistant (SU.86.86). Next, we demonstrated the specificity and sensitivity of ⁶⁸Ga-CBP8 to the deposited collagen in resected human PDAC and pancreas tissues. Eight male participant (49-65 y) with newly diagnosed PDAC underwent dynamic ⁶⁸Ga-CBP8 PET/MRI, and five underwent follow up ⁶⁸Ga-CBP8 PET/MRI after completing standard CRT. PET parameters were correlated with tumor collagen content and markers of response on histology. <b>Results:</b> ⁶⁸Ga-CBP8 showed specific binding to PDAC compared to non-binding ⁶⁸Ga-CNBP probe in two mouse models of PDAC using PET imaging and to resected human PDAC using autoradiography (P < 0.05 for all comparisons). ⁶⁸Ga-CBP8 PET showed 2-fold higher tumor signal in mouse models following FOLFIRINOX treatment in PANC-1 and PDAC6 models (P < 0.01), but no significant increase after treatment in FOLFIRINOX resistant SU.86.86 model. ⁶⁸Ga-CBP8 binding to resected human PDAC was significantly higher (P < 0.0001) in treated versus untreated tissue. PET/MRI of PDAC patients prior to CRT showed significantly higher ⁶⁸Ga-CBP8 uptake in tumor compared to pancreas (SUV_mean: 2.35 ± 0.36 vs. 1.99 ± 0.25, P = 0.036, n = 8). PET tumor values significantly increased following CRT compared to untreated tumors (SUV_mean: 2.83 ± 0.30 vs. 2.25 ± 0.41, P = 0.01, n = 5). Collagen deposition significantly increased in response to CRT (59 ± 9% vs. 30 ± 9%, P=0.0005 in treated vs. untreated tumors). Tumor and pancreas collagen content showed a positive direct correlation with SUV_mean (R² = 0.54, P = 0.0007). <b>Conclusions:</b> This study demonstrates the specificity of ⁶⁸Ga-CBP8 PET to tumor type I collagen and its ability to differentiate responders from non-responders based on the dynamic changes of fibrosis in PDAC. The results highlight the potential use of collagen PET as a non-invasive tool for monitoring response to treatment in patients with PDAC.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}