1.Preventive treatment of latent tuberculosis infections in schools clusters in Hefei during 2022-2024
GUO Ce, ZHANG Qiang, QIAN Bing, CHEN Shuangshuang, HE Yuqin, XU Rui, LI Zhen, ZHAO Cunxi, WU Jinju
Chinese Journal of School Health 2026;47(3):421-424
Objective:
To analyze the school tuberculosis (TB) outbreaks and preventive treatment in Hefei from 2022 to 2024, so as to provide reference for TB prevention and control in schools.
Methods:
Data were collected on all school based TB outbreaks occurring during 2022-2024 in Hefei, defined as ≥2 epidemiologically linked TB cases within the same school during a single semester. Statistical analyses were performed using the Chi square test.
Results:
Close contacts exhibited significantly higher TB incidence (2.88%) and latent mycobacterium tuberculosis infection (LTBI) rates (13.80%) in the school TB outbreaks, compared to non close contacts (0.12% and 2.63%, respectively). Among close contacts, secondary school students showed lower TB incidence (0.48%) and LTBI prevalence (3.42%) than both primary school or younger children (0.68%, 6.95%) and college students ( 0.78% , 6.50%), with statistically significant differences ( χ 2=360.91, 6.37; 791.71, 102.03, all P <0.05). The proportion of LTBI individuals recommended for preventive therapy was higher in primary school or younger groups (98.59%) than in secondary (95.25%) or college students (86.34%) ( χ 2=25.86, P <0.01). However, among those recommended, close contacts had higher uptake (85.82%) and completion rates (87.25%) of preventive therapy than non close contacts (69.63% and 70.57%); similarly, secondary school students demonstrated higher uptake (91.21%) and completion rates (86.45%) compared to primary school or younger (88.57%, 83.87%) and college students (57.28%, 64.08%) ( χ 2=30.52, 26.72; 125.17, 38.84, all P <0.01). Subsequent TB incidence among LTBI close contacts (13.30%) and among those who did not complete preventive therapy (22.73%) were significantly higher than among non close contacts (2.80%, 2.41%), respectively ( χ 2=32.19, 13.87, both P <0.05).
Conclusions
In school TB outbreaks, close contacts face higher LTBI prevalence and subsequent TB risk than non close contacts. College students show notably low adherence to preventive therapy. It is necessary to take targeted measures to improve the compliance of preventive measures among students.
2.Polypeptide-based Nanocarriers for Oral Targeted Delivery of CAR Genes to Pancreatic Cancer
Feng XIN ; Jian REN ; Zhao-Zhen LI ; Quan FANG ; Rui-Jing LIANG ; Lan-Lan LIU ; Lin-Tao CAI
Progress in Biochemistry and Biophysics 2026;53(2):431-441
ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.
3.Polypeptide-based Nanocarriers for Oral Targeted Delivery of CAR Genes to Pancreatic Cancer
Feng XIN ; Jian REN ; Zhao-Zhen LI ; Quan FANG ; Rui-Jing LIANG ; Lan-Lan LIU ; Lin-Tao CAI
Progress in Biochemistry and Biophysics 2026;53(2):431-441
ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.
4.Application of zero-trust architecture in hospital smart-management platform
You-qiong CHEN ; Bo YANG ; Zhen-qi ZHANG ; Lin-jie LI ; Rui SHI
Chinese Medical Equipment Journal 2025;46(8):50-57
Objective To investigate the application and effectiveness of a zero-trust network architecture(ZTNA)in a hospital's smart-management platform,providing a practical reference for network-architecture optimization in smart-hospital initiatives.Methods A single-arm mode was involved in the deployment of ZTNA.An encrypted tunnel was established by the zero-trust proxy gateway,and the components for zero-trust terminal security,behavior management,firewall,identity authentication,security operation and analysis center were synergized with the help of a logical bus to form a security protection system of end-to-end trust assessment,dynamic access control,micro-isolation and visualization,and the integration and access to the hospital's intelligent management platform were realized by means of ticket injection.Results ZTNA markedly enhanced data protection for the platform,and significantly improved user experience by simplified authentication and enhanced support for mobile operation.Conclusion ZTNA ensures the security of kinds of hospital business systems,and lays a foundation for large comprehensive hospitals to construct cross-region,cross-institution and multi-center medical information platforms and open data sharing modes.[Chinese Medical Equipment Journal,2025,46(8):50-57]
5.Case report and literature review of myocardial infarction caused by myocardial bridge
Xiao-qing KOU ; Yi-rong GAN ; Yun-long ZHANG ; Ding-xiong XIE ; Rui MAO ; Tian-xiang LIANG ; Xiao-li YANG ; Yan-zhen WANG
Chinese Journal of Interventional Cardiology 2025;33(2):111-116
Medical therapy and surgical intervention are the two primary approaches for treating myocardial bridge.However,there remains controversy regarding the use of coronary artery bypass grafting(CABG)and myocardial bridge unroofing.Here,we report a case of myocardial infarction following CABG in a patient with a myocardial bridge.The patient was admitted to Lanzhou First Peopie's Hospital with persistent chest pain,chest tightness,and shortness of breath lasting 2 hours.Physical examination revealed no significant abnormalities.Electrocardiography(ECG)indicated extensive anterior wall myocardial infarction.Laboratory findings showed myoglobin levels of 140.1 ng/ml and troponin Ⅰ levels of 2.59 ng/ml,with no other significant abnormalities.The initial diagnosis was acute extensive anterior wall myocardial infarction.Emergency coronary angiography revealed a myocardial bridge in the mid-segment of the left anterior descending artery(LAD).Emergency CABG using the left internal mammary artery to the LAD was performed,leading to symptomatic improvement,and the patient was discharged in stable condition.However,the patient experienced a recurrent myocardial infarction seven years post-surgery and received secondary preventive medical therapy.The patient is currently under ongoing follow-up care.CABG is an effective treatment for myocardial bridge.However,based on the case reported in this study,we recommend careful evaluation of whether a patient may benefit from CABG.
6.Study on the effectiveness and safety of a novel intravascular shock wave balloon for pre-treatment of severe coronary artery calcification lesions
Rui-tao ZHANG ; Zhen-yu TIAN ; Yong ZENG ; Guo-sheng FU ; Li XU ; Jian LIU ; Jian-ping LI ; Zhi-hui ZHANG ; Xin-qun HU ; Xiang CHENG ; Wen LU ; Ming CUI ; Yi-da TANG
Chinese Journal of Interventional Cardiology 2025;33(2):61-70
Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30%and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P<0.001],the degree of stenosis was significantly reduced[(13.24±6.60)%vs.(65.18±10.59)%,P<0.001].Procedural success was achieved in 100%of cases,and device success was 98.8%.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P<0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P<0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P<0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P<0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.
7.Long-term follow-up of percutaneous pulmonary valve implantation using domestic self-expanding valve-prospective single-center experience
Qian-bei HE ; Qiao LI ; Yi-jian LI ; Rui-tao LI ; Bo-feng CHAI ; Zhi-cheng CHEN ; Zhi-xiang YU ; Zhen-gang ZHAO ; Yuan FENG
Chinese Journal of Interventional Cardiology 2025;33(5):241-248
Objective To explore the long-term efficacy of percutaneous pulmonary valve implantation(PPVI)and the durability of the domestic self-expanding Venus P valve.Methods A total of 8 patients with post-surgical right ventricular outflow tract(RVOT)dysfunction,who were admitted to hospital from October 2014 to July 2016 and deemed anatomically suitable for PPVI with self-expanding valve,were included prospectively.Clinical,imaging,procedural and follow-up data were analyzed.The survival rates,perioperative and long-term complication rates,long-term efficacy of PPVI,and long-term function of Venus P in 8 patients were evaluated.The immediate procedural results were evaluated by clinical implant success rate,which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation<moderate and peak trans-pulmonary pressure gradient<40 mmHg.Results A total of 8 patients were included,with 7 females,aged 14 to 36 years.The initial diagnosis included post-surgical Tetralogy of Fallot(5 cases),post-surgical Trilogy of Fallot(1 case),post-surgical Quadricuspid pulmonary valve stenosis(1 case)and post-surgical Double-Outlet Right Ventricle(1 case).The indications of PPVI included RVOT-pulmonary obstruction and regurgitation(1 case)and isolated regurgitation(7 cases).Clinical implant success was achieved in all of the 8 patients with firmly fixed valve,and there were no such complications as valve detachment,displacement or stent fracture.All patients experienced significant symptom relief after the procedure.The right ventricular end-diastolic volume index(RVEDVi)measured by CMR 6 months after PPVI showed a significant decrease compared to preprocedural values[(89.99±13.85)ml/m2 vs.(144.93±11.28)ml/m2,P=0.001].Postoperative pulmonary regurgitation were significantly improved or disappeared in all patients,and there was no statistically significant difference in the average peak pressure gradient measured by echocardiogram between preoperative and the latest follow-up[(23.25±8.39)mmHg vs.(18.75±6.28)mmHg,P=0.210].Over an average follow-up period of(9.25±0.71)years,1 case of infective endocarditis occurred 5 years after PPVI.During the follow-up,no death,deterioration of heart failure,malignant arrhythmia or other serious complications were observed.All patients completed 8-year follow-up,and 3 completed 10-year follow-up.All patients were graded as NYHA functional class one at the latest follow-up.Conclusions PPVI using the domestically produced self-expanding Venus P is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable anatomy.Our study confirms the long-term efficacy and durability of Venus P from multiple perspectives,and no severe stent fracture occurred without pre-stent implantation in the native RVOT.
8.Correlation between serum zinc level and prognosis of patients with sepsis
Xiao-Gang WANG ; Jia-Jun MA ; Rui-Xin ZHU ; Li-Bing ZHOU ; Sai-Hu HUANG ; Shui-Yan WU ; Wen-Si NIU ; Jie HUANG ; Zhen-Jiang BAI
Parenteral & Enteral Nutrition 2025;32(5):278-282
Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725~0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.
9.Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique (version 2025)
Sihao HE ; Junchao XING ; Tongwei CHU ; Zhengqi CHANG ; Xigao CHENG ; Fei DAI ; Xiaobing JIANG ; Jie HAO ; Jiang HU ; Jinghui HUANG ; Tianyong HOU ; Fei LUO ; Bo LIAO ; Changqing LI ; Lei LIU ; Guodong LIU ; Peng LIU ; Sheng LU ; Weishi LI ; Yang LIU ; Zhen LIU ; Wei MEI ; Peifu TANG ; Bing WANG ; Bing WANG ; Ce WANG ; Hongli WANG ; Liang WANG ; Shengru WANG ; Xiaobin WANG ; Yang WANG ; Yingfeng WANG ; Zheng WANG ; Jianzhong XU ; Guoyong YIN ; Haiyang YU ; Qiang YANG ; Zhaoming YE ; Bin ZHANG ; Chengmin ZHANG ; Jun ZOU ; Qiang ZHOU ; Min ZHAO ; Rui ZHOU ; Xiaojun ZHANG ; Yongfei ZHAO ; Zhongrong ZHANG ; Zehua ZHANG ; Yingze ZHANG
Chinese Journal of Trauma 2025;41(11):1035-1047
For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.
10.Combination of hyaluronidase and pH-responsive, IR780-loaded photosensitive micelle enhanced anticancer effect in triple-negative breast cancer
Rui YANG ; Qinghua WANG ; Lan MING ; Su LI ; Zhen JIA ; Jiuda ZHAO ; Daozhen CHEN
Chinese Journal of Oncology 2025;47(9):885-895
Objectives:To investigate the enhancement of tumor penetration and photodynamic therapy (PDT) efficacy in triple-negative breast cancer by hyaluronidase (HAase) using a novel pH-responsive IR780-loaded photosensitive micelle.Methods:The pH-responsive IR780-loaded photosensitive micelles were prepared using the nanoprecipitation method, and their morphology, size, and encapsulation efficiency were characterized. The in vitro stability and pH-responsive drug release of the micelles were also evaluated. The cytotoxicity of the micelles on triple-negative breast cancer cells (MDA-MB-231) was assessed using a cell counting kit. A nude mouse breast cancer model was established, and HAase was injected intratumorally 24 hours before intravenous injection of the photosensitive micelles. The effect of HAase on the biodistribution and tumor uptake of the micelles was detected using small animal in vivo imaging. CD31 and HIF-1α immunofluorescence staining were performed to investigate the mechanism of HAase-enhanced tumor penetration. The body weight and tumor volume of the mice were measured, and necrosis and apoptosis of tumor tissues were assessed using HE staining and TUNEL staining, respectively. Results:Transmission electron microscopy showed that the micelles had a uniform particle size of approximately 60-70 nm, with a hydrated particle size of (98.03±0.22) nm. The IR780 encapsulation efficiency was 74.15%, with a drug loading content of 2.07%. After 7 days at 4 ℃, there was no significant change in hydrated particle size ( P=0.062). The 24-hour release rates of the micelles in PBS at pH 7.4 and 6.5 were (2.41±0.21)% and (43.69±2.09)%, respectively, showing a significant difference ( P<0.000 1). The cytotoxicity assay revealed that the cell viability in the micelles group without light exposure was significantly higer than that in the micelles group under light exposure [(97.00±5.38)% vs. (53.27±9.00)%, P=0.000 2]. The micelles were able to target and accumulate in the tumor tissue, and this accumulation increased significantly with HAase treatment. CD31 and HIF-1α immunofluorescence staining indicated that the CD31 signal was enhanced [(0.27±0.05)% vs. (4.57±0.27)%, P<0.000 1] and the HIF-1α signal was reduced [(5.14±0.38)% vs. (0.08±0.04)%, P<0.000 1] in the HAase-treated group compared to that in the micelle-only group. After 11 days of treatment with HAase combined with photosensitive micelles, there was no statistically significant difference in mouse body weight ( P>0.05). However, the tumor volume inhibition rate in the HAase-micelle-mediated PDT group was significantly higher than that in the micelle-mediated PDT group [(87.66±6.37)% vs. (25.34±12.63)%, P=0.002]. Histological staining showed a significant increase in tumor cell necrosis and apoptosis in the HAase-micelle-mediated PDT group. Conclusion:HAase enhances the deep tumor penetration and targeted accumulation of pH-responsive IR780-loaded photosensitive micelles, significantly improves the efficacy of photodynamic therapy in triple-negative breast cancer.


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