基于共价有机框架的仿生光动力学治疗试剂的构建

共价有机框架(COF)是一类新兴的多孔有机聚合物,因其具有较大的比表面积、有序的孔道结构以及良好的生物相容性,已成为具有潜力的纳米药物载体.制备了基于COF纳米颗粒的仿生纳米复合物,负载光敏剂孟加拉玫瑰红(RB),并包裹癌细胞膜(CMV)对该复合物进行仿生修饰.结果表明:制备的COF/RB@CMV纳米复合物具有良好的生物兼容性,能够被肿瘤细胞有效摄取,并在光照激活条件下产生对细胞具有高毒性的活性氧化物(ROS),进而起到了杀伤肿瘤细胞的作用.提出了一种新的基于COF的仿生纳米平台用作光动力学治疗(PDT)试剂.

类风湿性关节炎的动物模型

本文对在光动力疗法治疗类风湿性关节炎的研究中有关的动物模型的制作、发病过程、病理、发病原因及应用作一系统论述。

卟吩-f二甲酯合成及其反应机理研究

以叶绿素-a为起始原料,经酸性剔除中心金属镁离子得到脱镁叶绿酸-a甲酯.再经过空气氧化和重排反应将其转变为红紫素18-甲酯,在碱性条件下实施开环和脱羧反应,分别得到卟吩p6三甲酯、卟吩-f二甲酯.选择焦脱镁叶绿酸-a甲酯为起始原料,乙醇钠存在条件下进行空气氧化反应,则分别得到15-甲酰基卟吩-f二甲酯和卟吩-f二甲酯.表征了反应产物的化学结构,讨论和提出了可能的反应机理.

(3E/Z,13~1E/Z)焦脱镁叶绿酸-a甲酯13~1-酮肟的合成

以焦脱镁叶绿酸-a甲酯(MPP-a)为起始原料,经四氧化锇氧化形成焦脱镁叶绿酸-d甲酯,将其3-位甲酰基保护后与盐酸羟胺作用得到E-环成肟;利用3-位甲酰基与氯化苄基三苯基膦的Wittig反应,完成(3E/Z,131E/Z)-3b-苯基焦脱镁叶绿酸-a甲酯131-酮肟的合成及其异构体的分离.所合成的新化合物均经UV、IR、1HNMR及元素分析证明其结构.

Temperature-feedback two-photon-responsive metal-organic frameworks for efficient photothermal therapy

The realization of real-time thermal feedback for monitoring photothermal therapy(PTT)under near-infrared(NIR)light irradiation is of great interest and challenge for antitumor therapy.Herein,by assembling highly efficient photothermal conversion gold nanorods and a temperature-responsive probe((E)-4-(4-(diethylamino)styryl)-1-methylpyridin-1-ium,PyS)within MOF-199,an intelligent nanoplatform(AMPP)was fabricated for simultaneous chemodynamic therapy and NIR light-induced temperature-feedback PTT.The fluorescence intensity and temperature of the PyS probe are linearly related due to the restriction of the rotation of the characteristic monomethine bridge.Moreover,the copper ions resulting from the degradation of MOF-199 in an acidic microenvironment can convert H_(2)O_(2)into•OH,resulting in tumor ablation through a Fenton-like reaction,and this process can be accelerated by increasing the temperature.This study establishes a feasible platform for fabricating highly sensitive temperature sensors for efficient temperature-feedback PTT.

酸碱条件下脱镁叶绿酸-a甲酯的空气氧化反应

以对叶绿素 a甲酯 1为原料 ,在碱性条件下 ,其E 环经空气氧化发生重排而构成内酯 ,生成紫红素 18甲酯的镁铬合物 ,先后经硫酸脱金属镁离子和重氮甲烷酯化形成紫红素 18酯 3,在酸性条件下对 1进行空气氧化 ,其 132 位的氢原子被氧化而转变为羟基 ,生成 (S) 和 (R) 132 羟基脱镁叶绿 a甲酯异构体 4a和 4b 分离和表征了氧化产物 ,并根据反应条件提出可能的反应机理 所得到的氧化产物 叶绿酸衍生物均经UV、IR。

3-烷（酰基）取代-13^1-去氧焦脱镁叶绿酸-a甲酯的合成

以焦脱镁叶绿酸-a甲酯为起始原料,通过硼氢化钠对其E-环羰基实施还原而得到131-去氧焦脱镁叶绿酸-a甲酯,再选用四氧化锇对3-位乙烯基进行氧化,生成的131-去氧焦脱镁叶绿酸-d甲酯,再利用3-位甲酰基与正丁基基溴化镁或者环戊基溴化镁的格氏反应得到3-烷羟基卟吩.最后经氧化或者脱水反应,分别得到3-丁酰基和3-环戊亚甲基取代的131-去氧焦脱镁叶绿酸衍生物.所合成的新化合物均经UV,IR,1H NMR及元素分析证明其结构.

13^1-烷亚基-13^1-去氧焦脱镁叶绿酸-α甲酯的合成

以焦脱镁叶绿酸-α甲酯为起始原料,通过与对称直链烷基溴化镁或者环己基溴化镁进行格氏反应,将131-位羰基转化为烷羟基,经脱水在E-环形成环外碳碳双键,完成双烷亚甲基取代的131-去氧焦脱镁叶绿酸衍生物的合成。所合成的新化合物均经UV,IR,1H NMR及元素分析证明其结构。

姜黄素与焦脱镁叶绿酸-α甲酯的Knoevenagel反应研究

以脱镁叶绿酸-a甲酯1为原料,在酸性条件下加热,将其转化为焦脱镁叶绿酸-a甲酯2.选择四氧化锇为氧化剂将其3-位乙烯基氧化成甲酰基,在碱性条件下,与姜黄素进行Knoevenagel缩合反应,得到联有姜黄素化学结构的卟吩衍生物4.所得叶绿素衍生物均经UV、IR1、H NMR及元素分析证明其分子结构..

Photodynamic therapy prolongs metal stent patency in patients with unresectable hilar cholangiocarcinoma

AIM:To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC). METHODS:This was a retrospective analysis of patients with hilar CC referred to our institution from December, 1999 to January, 2011. Out of 232 patients, thirty-three patients with unresectable hilar CC were treated. Eighteen patients in the PDT group were treated with uncovered metal stents after one session of PDT. Fifteen patients in the control group were treated with metal stents alone. Porfimer sodium (2 mg/kg) was administered intravenously to PDT patients. Fortyeight hours later, PDT was administered using a diffusing fiber that was advanced across the tumor by either endoscopic retrograde cholangiopancreatography or percutaneous cholangiography. After performance of PDT, uncovered metal stents were inserted to ensure adequate decompression and bile drainage. Patient survival rates and cumulative stent patency were calculated using Kaplan-Meier analysis with the log-rank test. RESULTS:The PDT and control patients were comparable with respect to age, gender, health status, pretreatment bilirubin, and hilar CC stage. When compared to control, the PDT group was associated with significantly prolonged stent patency (median 244 ± 66 and 177 ± 45 d, respectively, P = 0.002) and longer patient survival (median 356 ± 213 and 230 ± 73 d, respectively, P = 0.006). Early complication rates were similar between the groups (PDT group 17%, control group 13%) and all patients were treated conservatively. Stent malfunctions occurred in 14 PDT patients (78%) and 12 control patients (80%). Of these 26 patients, twenty-two were treated endoscopically and four were treated with external drainage. CONCLUSION:Metal stenting after one session of PDT may be safe with acceptable complication rates. The PDT group was associated with a significantly longer stent patency than the control group in patients with unresectable hilar CC.

5-aminolaevulinic Acid-photodynamic Therapy for the Treatment of Cervical Condylomata Acuminata

Objective To investigate the efficacy and safety of photodynamic therapy （PDT） with topical 5-aminolaevulinic acid （ALA） on cervical condylomata acuminata. Methods Patients with cervical condylomata （n=30） were allocated into primary and recurrent group, and were given topical ALA under occlusive dressing for 3 hours followed by irradiation with semiconductor laser at a dose of 100 Jcm 2 and a power of 100 roW. The treatment was repeated 7 days later if the lesion was not completely removed after the first treatment. Complete response rate and recurrence rate of wart lesions as well as rate of adverse reaction were analyzed. Results The total complete response rate of PDT was 100% and the total recurrence rate was 5% after 3 months of follow-up. Recurrence rate of recurrent group was significantly lower than that of prior managements （100%, P〈0.01）. The side effects of PDT in patients mainly included mild burning and/or stinging restricted to the illuminated areas, and was significant lower than their own control （25% vs. 100%, P〈0.05）. Conclusion Compared with conventional therapies, topical application of ALA-PDT is a simple, effective, safe, well-tolerated, and low recurrence rate treatment for cervical condylomata acuminata.

Early apoptosis and cell death induced by ATX-S10Na(Ⅱ)-mediated photodynamic therapy are Bax- and p53-dependent in human colon cancer cells

AIM： To investigate the roles of Bax and p53 proteins in photosensitivity of human colon cancer cells by using lysosome-localizing photosensitizer, ATX-S10Na （Ⅱ）. METHODS： HCT116 human colon cancer cells and Bax-null or p53-null isogenic derivatives were irradiated with a diode laser. Early apoptosis and cell death in response to photodynamic therapy were determined by MTT assays, annexin Ⅴ assays, transmission electron microscopy assays, caspase assays and western blotting. RESULTS： Induction of early apoptosis and cell death was Bax- and p53-dependent. Bax and p53 were required for caspase-dependent apoptosis. The levels of anti-apoptotic Bcl-2 family proteins, Bcl-2 and Bcl-xL, were decreased in Bax- and p53-independent manner. CONCLUSION： Our results indicate that eady apoptosis and cell death of human colon cancer cells induced by photodynamic therapy with lysosome-localizing photosensitizer ATX-S10Na （Ⅱ） are mediated by p53- Bax network and low levels of Bcl-2 and Bcl-xL proteins. Our results might help in formulating new therapeutic approaches in photodynamic therapy.

In Vitro Lethal Effect of Photodynamic Therapy on Human Pancreatic Cancer Cells and Its Major Influencing Factors

OBJECTIVE To investigate the in vitro lethal effect of photo- dynamic therapy （PDT） using the photosensitizer hematoporphyrin on the human pancreatic cancer cell line Panc-1, the major influencing factors and the mechanisms of treatment. METHODS Three factors--the time needed for photosensitizer and cell incubation, the photosensitizer concentration （PhoC） and the exposure dose （ExpD）--were examined with different levels of these factors. Optical density （OD） was used as a measure of CCK-8 in the experiment, and was converted to the rate of cell survival. The separate effect of each factor on the photodynamic action was studied, and the interactions were investigated. The effects of different incubation times and PhoC levels on the fluorescence intensity （FI） of the intracellular photosensitizer were determined, and the mechanisms of these factors leading to the therapeutic effects of PDT discussed. RESULTS An increase in the photosensitizer and cell incubation time, an increase of PhoC, and enhancement of the ExpD, produced a corresponding decrease in the rate of Panc-1 cell survival after PDT （P 〈 0.05）. PDT achieved its maximum lethal effects 16 h after starting the incubation, with a PhoC of 10 mg/L and an ExpD of 20 J/cm2; at these levels a synergistic interaction between PhoC and the ExpD occurred, decreasing the cell survival rate （P 〈 0.05）. Neither simple administration of photosensitizer without ExpD （0 J/cm2） or illumination in the absence of PhoC （0 mg/L） affected the rate of cell survival （P 〉 0.05）. With an increase of PhoC and lengthening of the incubation time, the FI of the intracellular photosensitizer accordingly increased （P 〈 0.05）, and attained its maximum value at a PhoC of 10 mg/L and 36 h after the incubation. With an increase of PhoC, the FI of the photosensitizer, hematoporphyrin, in the solution increased progressively at first and then decreased （fluorescence quenching）. CONCLUSION PDT with the photosensitizer hematoporphyrin has clear lethal effects on the human pancreatic cancer cell line Panc-1, but the presence of a photosensitizer and laser irradiation by themselves do not have independent lethal effects. The three influencing factors--the time for photosensitizer and cell incuba- tion, PhoC and ExpD--correlate positively with the PDT response, within certain limits. Beyond these limits, the PDT response does not significantly increase. The main mechanism of the PDT response lies in the effect of these factors on the level of the intracellular photosensitizer and the fluorescence quenching of the photosensitizer. A synergistic effect exists between PhoC and ExpD.

Photodynamic Therapy for Gynecological Diseases and Breast Cancer

Photodynamic therapy （PDT） is a minimally invasive and promising new method in cancer treatment. Cytotoxic reactive oxygen species （ROS） are generated by the tissueqocalized non-toxic sensitizer upon illumination and in the presence of oxygen. Thus, selective destruction of a targeted tumor may be achieved. Compared with traditional cancer treatment, PDI has advantages including higher selectivity and lower rate of toxicity. The high degree of selectivity of the proposed method was applied to cancer diagnosis using fluorescence. This article reviews previous studies done on PDT treatment and photodetection of cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, ovarian and breast cancer, and PDT application in treating non-cancer lesions. The article also highlights the clinical responses to PDT, and discusses the possibility of enhancing treatment efficacy by combination with immunotherapy and targeted therapy.

Metal stenting to resolve post-photodynamic therapy stricture in early esophageal cancer

Photodynamic therapy (PDT) is an established endoscopic technique for ablating Barrett's esophagus with high-grade dysplasia or early-stage intraepithelial neoplasia. The most common clinically significant adverse effect of PDT is esophageal stricture formation. The strictures are usually superficial and might be dilated effectively with standard endoscopic accessories, such as endoscope balloon or Savary dilators. However, multiple dilations might be required to achieve stricture resolution in some cases. We report the case of stricture that recurred after dilation with a bougie, which was completely relieved by a self-expandable metal stent.

Synergetic anticancer effect of combined gemcitabine and photodynamic therapy on pancreatic cancer in vivo

AIM： To investigate the anti-tumor effects of combined cytotoxic drug （gemcitabine） and photodynamic therapy （PDT） on human pancreatic cancer xenograft in nude mice.METHODS： Human pancreatic cancer cell line SW1990 was used in the investigation of the in vivo effect of combined gemcitabine and PDT on human pancreatic cancer xenograft in mice. Sixty mice were randomly allocated into a control group （without treatment）, photosensitizer treatment group （2 mg/kg photosan, without illumination）, chemotherapy group （50 mg/kg gemcitabine i.p.）, PDT group （2 mg/kg photosan ＋ laser irradiation） and combined treatment group （photosan ＋ chemotherapy）, with 12 mice in each group. Tumor size was measured twice every week. Anti-tumor activity in different groups was evaluated by tumor growth inhibition （TGI）RESULTS： No significant anti-tumor effect was observed either in photosensitizer treatment group or in chemotherapy group. PDT led to necrosis in cancer lesions and significantly reduced tumor volume compared with photosensitizer on day 6 and at the following time points after initialization of therapy （0.24 ± 0.15-0.49 ± 0.08 vs 0.43 ± 0.18-1.25± 0.09, P 〈 0.05）. PDT significantly reduced tumor volume in combined treatment group compared with photosensitizer treatment group （0.12 ± 0.07-0.28 ± 0.22 vs 0.39 ± 0.15-2.20 ± 0.12, P 〈 0.05）, small dose chemotherapy group （0.12 ± 0.07-0.28 ± 0.12 vs 0.32 ± 0.14-1.16 ± 0.08, P 〈 0.05） and control group （0.12 ± 0.07-0.28 ± 0.12 vs 0.43 ± 0.18-1.25 ± 0.09, P 〈 0.05）. TGI was higher in the combined treatment group （82.42%） than in the PDT group （58.18%）.CONCLUSION： PDT has a significant anti-tumor effect, which is maintained for a short time and can be significantly enhanced by small doses of gemcitabine.

Enhancement of the Photodynamic Therapy Effect on Streptococcus Mutans Biofilm

Biofilm is a community of bacteria, less susceptible to traditions treatments. Although photodynamic therapy （PDT） is a very effective way to microorganism inactivation, in biofilm it is not as efficient as it is in planktonic bacteria cultures. The increment of an element to increase the effectiveness of PDT was our aim. Therefore, this in vitro study evaluates the susceptibility ofa biofilm formed by Streptococcus mutans on metallic surface of orthodontic accessories under the application of PDT with a surfactant. Samples obtained from blades of orthodontic bands （NiCr）, where used as adhesion surface for the biofilm. They were treated with 1 mg/ml of curcumin, with 0.1% of sodium dodecyl sulfate and exposed to 30 J/cm^2 of light （455 nm）. Eight experimental groups were studied, including the positive and negative controls. The results show that the group with PDT and surfactant had a significant decrease （p 〈 0.001） in viability. In this case, the reduction observed was of 5.6 log10 （CFU/ml） in comparison to the control group. We have shown that, even though the biofilm is very tough and complex structure, we are able to promote almost the complete inactivation ofS. mutans in systems similar to an orthodontic treated patient＇s mouth.

Comparison of photodynamic therapy for skin cancers and pre-cancers with δ-aminolevulinic acid

Objective:The aim of the study was to compare the effects of photodynamic therapy(PDT) with δ-aminolevulinic acid(ALA) for patients with different kinds of skin cancers and pre-cancers.Methods:The present study enrolled seventyfive cases,which included 17 cases of actinic keratosis(AK),9 cases of Bowen's disease,11 cases of superficial basal cell carcinomas(BCC),23 cases of nodule basal cell carcinomas and 15 cases of squamous cell carcinomas(SCC),and every patient had single lesion.All patients were treated with 20% ALA topically and He-Ne laser weekly for three times,and followed up 1-3 years.Results:After therapy,the rates of complete reaction(CR) were 100% in AK lesions,77.8% in Bowen's diseases,90.9% in superficial BCCs,47.8% in nodule BCCs,and 50.3% in SCCs,which had significant differences among these five kinds of lesions(H = 18.27,P < 0.05).The therapeutic effectiveness of ALA-PDT for AK was superior to that of Bowen's disease(Q = 4.364,P < 0.05),superficial BCC(Q = 5.55,P < 0.01),SCC(Q = 8.94,P < 0.01) and nodule BCC(Q = 17.91,P < 0.01);the effect of Bowen's disease was better than that of SCC(Q = 7.8,P < 0.01),nodule BCC(Q = 13.44,P < 0.01);the effect of superficial BCC was better than that of SCC(Q = 9.73,P < 0.01),nodule BCC(Q = 16.28,P < 0.01),but similar with Bowen's disease(Q = 0.96,P > 0.05);the effect of SCC was better than that of nodule BCC(Q = 17.74,P < 0.01).Conclusion:Our study shows that therapeutic effectiveness of ALA-PDT for AK is best in five diseases,and Bowen's disease and superficial BCC are secondary,while nodule BCC and SCC are at the bottom.

A Novel Regimen for Perioral Dermatitis by Photodynamic Therapy

Some patients with perioral dermatitis are not relieved despite many medications. These patients confront pain, psychological bother and social/occupational limitations. Being efficient for a wide variety of diseases including infectious inflammative degenerative or tumoral, photodynamic therapy holds a good chance to cure diseases of unknown origin, such as perioral dermatitis. This study presents the results of three women with chronic perioral dermatitis that persisted for years with partial response to medical regimen. They asked for photodynamic treatment to ease off their suffering. The duration of follow-up was up to five years. Following PDT （photodynamic therapy）, the patients discontinued medications, redness decreased and eruption disappeared. In these patients, a single PDT treatment provided prolonged relief of perioral dermatitis for up to three years. These data are encouraging but not sufficient. Further study is warranted.

Clinical Application of Photodynamic Therapy

Photodynamic therapy（PDT） is a new medical technology, the study on photodynamic therapy was in full swing in the past two decade. Scientists have made great progress in it. Photosensitizer,oxygen and light source play important role in photodynamic therapy. PDT is a light activated chemotherapy. A photon is adsorbed by a photosensitizer which moves the drug into an excited state. The excited drug can then pass its energy to oxygen to create a chemical radical called “singlet oxygen”. Singlet oxygen attacks cellular structures by oxidation. Such oxidative damage might be oxidation of cell membranes or proteins. When the accumulation of oxidative damage exceeds a threshold level,the cell begins to die. Photodynamic therapy allows selective treatment of localized cancer. PDT involves administration of a photosensitizer to the patients, followed by delivery of light to the cancerous region. The light activates the agent which kills the cancer cells. Without light,the agent is harmless. As a new therapy,photodynamic Therapy has great Advantage in treating cancers. 1. PDT avoids systemic treatment. The treatment occurs only where light is delivered, hence the patient does not undergo go needless systemic treatment when treating localized disease. Side-effects are avoided, from losing hair or suffering nausea to more serious complications. 2. PDT is selective. The photosensitizing agent will selectively accumulate in cancer cells and not in surrounding normal tissues. Hence ,there is selective targeting of the cancer and sparing of surrounding tissues. 3. when surgery is not possible. PDT kills cancer cells but does not damage collagenous tissue structures,and normal cells will repopulate these structures. Hence,if a patient has cancer in a structure that cannot be removed surgicaily（eg. ,the upper bronchi of the lung） ,PDT can still treat the site. 4. PDT is repeatable. Uniike radiation therapy,PDT can be used again and again. Hence,it offers a means of longterm management of cancer even if complete cure is not attainable.