1.Progress on carboxyl-substituted phthalocyanine photosen-sitizers and their drug delivery systems for photodynamic therapy.
Dan SHEN ; Hongjie HUANG ; Jincan CHEN ; Bowen LI ; Zhuo CHEN
Journal of Zhejiang University. Medical sciences 2025;54(4):500-510
Research in photodynamic therapy (PDT) primarily focuses on enhancing light penetration depth, improving oxygen supply, and optimizing photosensitizer delivery. Notably, the delivery efficiency of the photosensitizer is crucial for therapeutic efficacy. Carboxyl-substituted phthalocyanines, as important photosensitizing molecules, possess unique chemical modification sites that enable direct targeted delivery or integration into diverse delivery systems. Their synthesis predominantly employs mixed- or cross-condensation, selective synthesis, and axial modification strategies to introduce carboxyl groups. However, their inherent hydrophobicity significantly hinders effective delivery. To address this limitation, modifications with peptides or quaternary ammonium salt derivatives may facilitate precise delivery to tumor cells and pathogens. With advances in nanotechnology, carboxyl-substituted phthalocyanines can serve as key photosensitizer modules, effectively integrated into nanomaterials such as biomacromolecules, inorganic metals, and polymers for both active and passive delivery. Recently, researchers have exploited the π-π stacking and other intermolecular forces among carboxyl-substituted phthalocyanine molecules to drive their self-assembly into nano-micelles, enabling carrier-free delivery or co-delivery with other therapeutic agents for synergistic effects. This review systematically outlines the synthesis strategies for carboxyl-substituted phthalo-cyanines. Taking mono-carboxyl-substituted zinc phthalocyanine as a model molecule, the performance of three delivery modalities were compared: single-molecule targeted delivery, nanocarrier-encapsulated delivery, and carrier-free self-assembled delivery, in terms of PDT efficacy, biocompatibility, and imaging-guided tracing capabilities, to provide a systematic technical framework for the rational design of novel modular photosensitizers and to advance the clinical translation of PDT in precision oncology and anti-infective therapy.
Photochemotherapy/methods*
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Indoles/administration & dosage*
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Photosensitizing Agents/administration & dosage*
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Drug Delivery Systems
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Humans
2.Working memory deficits in Parkinson's disease mouse model
Tingting ZHAO ; Huating GU ; Miao ZHAO ; Tianzhi CHEN ; Yingjie AN ; Xian ZHANG ; Jincan HOU ; Peng CAO ; Linghui ZENG ; Chengyu LI
Chinese Journal of Pharmacology and Toxicology 2023;37(7):517-518
OBJECTIVE Parkinson's disease(PD)is a progressive neurodegenerative disease clinically char-acterized by dyskinesia,tremor,rigidity,abnormal gait,whereas 90%of patients with PD suffer from defects of the sense of smell before the appearance of the motor dysfunctions.However,the mechanism of olfactory disor-der is still not clear.METHODS We utilized olfaction based delayed paired association task in head-fixed mice.We focused on functional role of neural circuit using opto-genetic techniques.In addition,we viewed the synaptic transmission by slice physiological recording and count-ed the cell number of targeted circuits.RESULTS AND CONCLUSION In our experiments,olfactory working memory impairments were found in the PD mice,and the working memory impairment appeared before motor dys-functions.Furthermore,we also investigated the functional role of neural circuit for olfactory working memory in PD mice.Meanwhile,the excitatory post synaptic currents were decreased as a result of presynaptic release proba-bility suppression in PD mice.However cell loss wasn't found in working memory related circuit recently.These will provide a new idea of clinic diagnosis for PD.
3.Research advances in tibial insertion of posterior cruciate ligament and location of tibial tunnel
Zhen CHEN ; Lingpeng JIN ; Jian ZHANG ; Jincan ZHANG ; Yunxiao WANG ; Jiangtao DONG
Chinese Journal of Orthopaedic Trauma 2022;24(7):640-644
Posterior cruciate ligament (PCL) plays an important role in maintaining the stability of knee. PCL injury is often accompanied by serious axial and rotational instability, and severe PCL injury is likely to be combined with injuries to the anterior cruciate ligament, medial collateral ligament and other tissues which are often repaired by necessary posterior cruciate ligament reconstruction (PCLR) to restore their physiological functions. However, PCLR research is not as common as the research into the anterior cruciate ligament reconstruction, not only due to controversies in the anatomy and mechanics of PCL but also due to a higher failure rate and more complications following PCLR. This situation is closely related to the anatomical characteristics of the PCL tibial insertion. The present review deals with the anatomy, mechanics and clinical research of the PCL tibial insertion in order to provide more references for PCLR operators.
4.Impact of neoadjuvant chemotherapy on long-term prognosis for borderline resectable pancreatic cancer treated with combined allogeneic vascular replacement
Jincan HUANG ; Fei PAN ; Tao JIANG ; Jing WANG ; Qing CHEN ; Mengxiu HUANG ; Qiang HE ; Ren LANG
Chinese Journal of Hepatobiliary Surgery 2022;28(8):582-586
Objective:To evaluate the impact of neoadjuvant chemotherapy on long-term prognosis of patients with borderline resectable pancreatic cancer (BRPC) treated with combined allograft revascularization.Methods:The data of patients with BRCP who were treated at Beijing Chaoyang Hospital, Capital Medical University from March 2016 to March 2021 were retrospectively analysed. Of 52 patients who underwent radical surgery combined with allograft revascularization in this study, there were 24 males and 28 females, aged (60.3±10.6) years old. These patients were divided into two groups based on whether they received neoadjuvant chemotherapy before surgery. There were 19 patients in the neoadjuvant chemotherapy group and 33 patients in the vascular replacement group. Outpatient clinic and telephone follow-up were used. The clinical data and prognostic differences between the two groups were then analysed.Results:Of 52 patients who underwent surgery successfully, 14 patients (26.9%) developed postoperative complications. The incidence of postoperative pancreatic fistula was significantly lower in the neoadjuvant chemotherapy group than the vascular replacement group (0 vs. 21.2%, P<0.05). The median survivals were 15 and 13 months in the neoadjuvant chemotherapy and the vascular replacement groups, respectively, with a significant difference in cumulative postoperative survival between the two groups ( P=0.039). For patients with BRPC, CA19-9>400 U/ml ( RR=4.540, 95% CI: 2.332-8.836, P<0.001) was an independent risk factor for long-term survival after surgery. Conclusions:Neoadjuvant chemotherapy reduced the incidence of postoperative pancreatic fistula and improved survival prognosis in patients with BRPC. A high preoperative serum CA19-9 level was an independent risk factor for long-term survival in patients with BRPC.
5.Effect of tiotropium on urination disorder in benign prostatic hyperplasia patients with chronic obstructive pulmonary disease
Gang WANG ; Yi ZHAN ; Jincan HE ; Guang CHEN
The Journal of Practical Medicine 2017;33(3):459-461
Objective To study the effect of tiotropium on urination disorder in benign prostatic hyperplasia (BPH) patients with chronic obstructive pulmonary disease (COPD).Methods In our prospective pilot study,96 BPH patients with COPD patients were enrolled as the treatment group and another 25 similar cases as the control group:In the former group tiotropium was administered and the control group was not.The two groups were compared in terms of the score by the international Prostate Symptom Score(IPSS),the quality of life by QOL,maximum flow rate (Q-max),average flow rate (Q-ave),time to Q-max (TTQ-Max),prostate volume (PVR) and bladder voiding efficiency (BVE) after six months treatment.Results As compared to the control,after six months treatment,such indexes in the treatment group as IPSS (15.1 ± 4.1,16.3 ± 3.4 and 14.7 ± 3.1,P =0.864),QOL(3.9 ± 0.8,4.0± 0.8 and 4.0 ± 0.9,P =0.992),Q-Max(ml/s) (8.5 ± 2.9,10.9 ± 2.2 and 9.0 ± 2.4,P =0.214),Q-ave(ml/s) (3.9 ±1.2,5.0 ± 1.4 and 3.8 ± 0.9,P =0.054),TTQ-Max(s) (11.1 ± 5.6,11.2 ± 4.0 and 10.4 ± 5.1,P =0.424),PVR(mL)(56.8 ± 33.3,62.3 ± 30.5 and 57.4 ± 29.5,P =0.981),BVE(%) (75.6 ± 13.8,72.7 ± 10.5 and 74.3 ± 12.1,P =0.992).showed no significant differences.Conclusion Tiotropium does not adversely affect lower urinary tract functions in BPH patients with COPD.
6.Protective effects of salidroside on endothelial progenitor cells damaged by radiation
Shantao LIU ; Jincan ZHU ; Xiaoyu CHEN ; Gexiu LIU
Chinese Journal of Pathophysiology 2016;32(2):240-244
AIM:To explore the protective effects of salidroside on endothelial progenitor cells (EPCs) dam-aged by radiation and its mechanisms.METHODS:EPCs from normal peripheral blood were cultured in fibronectin-coated flasks with endothelial progenitor medium.The effects of salidroside on the viability, migration, adhesion and apoptosis of radiation-damaged EPCs were detected.The viability, apoptosis and migration of the cells were assayed by CCK-8 assay, flow cytometry and Transwell chamber experiment, respectively.The cell adhesion assay was performed by re-plating the cells on fibronectin-coated dishes, and then the adherent cells were counted.The expression of Akt protein in the cells was assessed by Western blotting.RESULTS:Salidroside improved the viability, and migratory and adhesive capacities of the EPCs, and decreased the apoptosis after radiation.Salidroside also increased the protein level of phosphorylated Akt.How-ever, the effects of salidroside on radiation-damaged EPCs were inhibited by phosphatidylinositol 3-kinase inhibitor LY294002.CONCLUSION: Salidroside protects EPCs from radiation damages and its mechanism is associated with en-hancing phosphatidylinositol 3-kinase/Akt signaling pathway.
7.Effect of salidroside on activity of endothelial progenitor cells and phos-phoinositide 3-kinase/Akt signaling pathway
Zhilan ZHOU ; Linjing WANG ; Gexiu LIU ; Jincan ZHU ; Xiaoyu CHEN ; Shantao LIU
Chinese Journal of Pathophysiology 2014;(7):1192-1195
AIM: To investigate whether salidroside has influence on the activities of endothelial progenitor cells (EPCs) and its mechanism.METHODS:Mononuclear cells from normal human peripheral blood were cultured in fi-bronectin coated flasks in endothelial progenitor medium .After 7 d, EPCs were characterized as adherent cells with acLDL-DiI uptaking and lectin binding by direct fluorescent staining .The proliferation and migration of EPCs were analyzed by MTT assay and Transwell chamber assay , respectively.The EPCs adhesion assay was performed by re-plating the cells on fibronectin-coated dishes , and then adherent cells were counted .NO and Akt protein were also detected .RESULTS:Sali-droside promoted EPCs proliferative , migratory and adhesive capacities in a concentration dependent manner .Salidroside also increased NO secretion , and the level of phosphorylated Akt protein .However , the effects of salidroside on EPCs were inhibited by phosphoinositide 3-kinase inhibitor LY294002.CONCLUSION:Salidroside regulates the activity of EPCs by phosphoinositide 3-kinase/Akt signaling pathway .
8.Effect of salidroside on radiation-induced bone marrow adipogenesis
Jincan ZHU ; Xiaoyu CHEN ; Chengcheng LIU ; Aizhen ZHU ; Shantao LIU ; Gexiu LIU
Chinese Journal of Radiological Medicine and Protection 2014;34(10):735-738
Objective To investigate the potential and underlying molecular mechanism of salidroside in ameliorating radiation-induced bone marrow adipogenesis and stimulating hematopoiesis.Methods The female BALB/c mice aged 6-7 weeks were randomly divided into normal control group,radiation group and salidroside group.The radiation group and salidroside group were irradiated with 6.0 Gy of 60Co γ-rays.The salidroside group was intraperitoneally injected with 30 mg· kg-1 · d-1 salidroside at 12 h and then every day until 8th d after radiation.The normal control group and radiation group were treated with equal volume of saline as control of salidroside.At 14 d after radiation,the mice weight,peripheral blood count,femur bone marrow histology,and the proportion of adipocyte area were measured,and the expressions of PPAR-γ and FABP4 were detected by q-PCR.Results After irradiation,the numbers of white blood cells,hemoglobin and platelet in peripheral blood were reduced obviously,and the percentage of adipocyte area was increased significantly.Compared with mice in the radiation group,salidroside inhibited adipogenesis and reduced the proportion of adipocyte area (t =13.31,P < 0.05) by reducing the expressions of PPAR-γ and FABP4 (t =8.64,13.19,P < 0.05).The number of white blood cells was partly recovered at 7 d after irradiation (t =5.80,P < 0.05).Both white blood cells and hemoglobinin in peripheral blood of the salidroside group were higher than those in the radiation group at 14 d after irradiation.Conclusions Salidroside could inhibit radiation-induced bone marrow adipogenesis and regulate bone marrow microenvironment,thereby promotes hematopoietic recovery in mice after radiation injury.
9.Identification of the polymorphs of clopidogrel bisulfate based on the steric morphology parameters of crystals.
Long CHEN ; Liuyi WANG ; Xianzhen YIN ; Jincan WANG ; Ruihao LIU ; Dan WANG ; Haiyan LI ; Weifeng ZHU ; Jiwen ZHANG
Acta Pharmaceutica Sinica 2013;48(9):1459-63
The crystal form of solid substance had intrinsic correlation with its three dimensional crystal morphology. Based on the characterization of the three dimensional crystal morphology of clopidogrel bisulfate, this research is to establish a model based on the three dimensional morphological parameters. The granular samples composed of polymorphs of clopidogrel bisulfate and microcrystalline cellulose (MCC) were scanned by synchrotron radiation X-ray microscopic CT technology (SR-microCT) and the three dimensional structural models for which were constructed. Seven groups of three dimensional morphological parameters were calculated. Finally, the mathematical model was established with the multi-layer perception (MLP) artificial neutral network methods to identify and predict the polymorphs of clopidogrel bisulfate. The success rate of the model prediction for the polymorphs of clopidogrel bisulfate was 92.7% and the area under the ROC curve was 96.2%. The polymorphs of drugs could be identified and predicted through the numerical description of the three dimensional morphology. The volume, number of the vertices and the surface area were the major determinants for the identification of the polymorphs of clopidogrel bisulfate.
10.Protective effect of 1,25-(OH)2D3 on radiation-induced bone marrow microenvironment injury
Xiaoyu CHEN ; Aizhen ZHU ; Chengcheng LIU ; Jincan ZHU ; Gexiu LIU
Chinese Journal of Radiological Medicine and Protection 2013;33(4):337-340
Objective To investigate the protective effect of 1,25-(OH) 2D3 on radiation-induced bone marrow microenvironment injury and to explore the related molecular mechanism.Methods Sixty 7-week old male BALB/c mice were randomly divided into control group without any treatment; radiation group exposed to 6.0 Gy 60Co γ-rays with DMSO,and 1,25-(OH)2 D3 + radiation group treated with 1,25-(OH)2D32.5 μg/kg dissolved in DMSO each day and 6 Gy of γ-rays.The body weight and peripheral white blood cells,femur bone marrow histology,and the proportion of adipocyte area were measured.The expression of peroxisome proliferator-activated receptor-gamma (PPARγ) was detected immunohistochemistrically at 8 d after irradiation.Results After irradiation,the number of white blood cells and the body weight decreased obviously,and the percentage of adipocyte area was increased significantly.Compared with radiation group,1,25-(OH)2D3 reduced the decrease rate of body weight (t =-2.23,-2.34,P < 0.05),partly recovered the number of white blood cells at 4 or 8 d after irradiation(t =-4.99,-4.46,P < 0.05),and reduced the proportion of adipocyte area (t =-3.75,-2.10,P < 0.05).With immunohistochemistrical assay,it was found that 1,25-(OH) 2D3 inhibited adipogenesis by reducing the expression of PPARγ.Conclusions 1,25-(OH) 2 D3 decreases radiationinduced adipogenesis and hence protects the bone marrow microenvironment from radiation damage.

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