摘要：Chlorin e6-pHLIPss-AuNRs, a gold nanorod-photosensitizer conjugate containing a pH （low） insertion peptide （pHLIP） with a disulfide bond which imparts extracellular pH （pHe）-driven tumor targeting ability, has been successfully developed for bimodal photodynamic and photothermal therapy. In this bimodal therapy, chlorin e6 （Ce6）, a second-generation photosensitizer （PS）, is used for photodynamic therapy （PDT）. Gold nanorods （AuNRs） are used as a hyperthermia agent for photothermal therapy （PTT） and also as a nanocarrier and quencher of Ce6. pHLIPss is designed as a pile-driven targeting probe to enhance accumulation of Ce6 and AuNRs in cancer cells at low pH. In Ce6- pHLIPss-AuNRs, Ce6 is close to and quenched by AuNRs, causing little PDT effect. When exposed to normal physiological pH 7.4, Ce6-pHLIPs^-AuNRs loosely associate with the cell membrane. However, once exposed to acidic pH 6.2, pHLIP actively inserts into the cell membrane, and the conjugates are translocated into cells. When this occurs, Ce6 separates from the AuNRs as a result of disulfide bond cleavage caused by intracellular glutathione （GSH）, and singlet oxygen is produced for PDT upon light irradiation. In addition, as individual PTT agent, AuNRs can enhance the accumulation of PSs in the tumor by the enhanced permeation and retention （EPR） effect. Therefore, as indicated by our data, when exposed to acidic pH, Ce6-pHLIPss-AuNRs can achieve synergistic PTT/PDT bimodality for cancer treatment.

摘要：Drug administration customized to individual cells could intrinsically address cancer heterogeneity and provide a safe and effective method for delivering personalized treatment. To accomplish this, we developed a smart nanodrug delivery system characterized by cancer cell-targeted drug delivery and intracellular biomarker-responsive drug activation. This system was composed of a long-nicked DNA duplex formed by tandem hybridization of two extended antisense oligonucleotides whose ends were separately blocked with a cancer cell-specific aptamer, AS1411,and a replaceable anti-biomarker probe(ABP). We demonstrated that this DNA nanodrug was directed to cancer cells with the guidance power of AS 1411 and then activated by the presence of a given intracellular biomarker. By using such a belt-and-braces strategy, this DNA nanodrug system could safely and efficiently accelerate apoptosis of target cancer cells. Moreover, since the expression level of biomarkers tends to indicate the specific physiological state of individual cells, biomarker-responsive activation of the nanodrug is expected to enable customized drug administration at the cellular level.

摘要：目的寻找筛查慢性肾脏病的有效策略,并描述慢性肾脏病的自然病程。设计横断面健康调查(HUNT Ⅱ研究)后的8年随访。地点挪威 Nord-TrΦndelag 县。对象 65604人(该国家≥20岁的成年人占70.6%)。主要研究终点指标终末期肾病(ESRD)发生率和心血管事件死亡率,二者通过联接到中心登记处的个人信息进行监测。结果人群中3069/65 604(4.7%)有慢性肾脏病(CKD)(估算肾小球滤过率55岁的人群,其中93.2%(92.4%～94.0%)有 CKD,发现1例 CKD则需要筛查8.7(8.5～9.0)人。美国 KDOQI 指南得出相似的筛查结果,英国慢性肾脏病指南的筛查结果仅为51.6%(49.6%～53.4%)。而只筛查既往有明确糖尿病史或高血压病史的人群的结果为44.2%(42.7%～45.7%),每发现1例CKD 需要筛查6人。在8年的随访中,3069例CKD 患者仅有38例进展为终末期肾病;而且,无高血压和糖尿病,女性,年龄≥70岁或筛查时肾小球滤过率(GFR)为45～59ml/min/1.73m^2者,他们发生 ESRD 的危险性尤其低。相比而言,心血管事件死亡率则很高,筛查时 GFR 为45～59,30～44和55岁的人群进行筛查是发现 CKD 患者最有效的策略,但是在这些患者中发生 ESRD 的危险性较低。