Enhanced In Vivo Tumor Detection by Active Tumor Cell Targeting Using Multiple Tumor Receptor‐Binding Peptides Presented on Genetically Engineered Human Ferritin Nanoparticles

Human ferritin heavy‐chain nanoparticle (hFTH) is genetically engineered to present tumor receptor‐binding peptides (affibody and/or RGD‐derived cyclic peptides, named 4CRGD here) on its surface. The affibody and 4CRGD specifically and strongly binds to human epidermal growth factor receptor I (EGFR) and human integrin αvβ3, respectively, which are overexpressed on various tumor cells. Through in vitro culture of EGFR‐overexpressing adenocarcinoma (MDA‐MB‐468) and integrin‐overexpressing glioblastoma cells (U87MG), it is clarified that specific interactions between receptors on tumor cells and receptor‐binding peptides on engineered hFTH is critical in active tumor cell targeting. After labeling with the near‐infrared fluorescence dye (Cy5.5) and intravenouse injection into MDA‐MB‐468 or U87MG tumor‐bearing mice, the recombinant hFTHs presenting either peptide or both of affibody and 4CRGD are successfully delivered to and retained in the tumor for a prolonged period of time. In particular, the recombinant hFTH presenting both affibody and 4CRGD notably enhances in vivo detection of U87MG tumors that express heterogeneous receptors, integrin and EGFR, compared to the other recombinant hFTHs presenting either affibody or 4CRGD only. Like affibody and 4CRGD used in this study, other multiple tumor receptor‐binding peptides can be also genetically introduced to the hFTH surface for actively targeting of in vivo tumors with heterogenous receptors.     

Red Blood Cell‐Facilitated Photodynamic Therapy for Cancer Treatment

Photodynamic therapy (PDT) is a promising treatment modality for cancer management. So far, most PDT studies have focused on delivery of photo­sensitizers to tumors. O₂, another essential component of PDT, is not artificially delivered but taken from the biological milieu. However, cancer cells demand a large amount of O₂ to sustain their growth and that often leads to low O₂ levels in tumors. The PDT process may further potentiate the oxygen deficiency, and in turn, adversely affect the PDT efficiency. In the present study, a new technology called red blood cell (RBC)‐facilitated PDT, or RBC‐PDT, is introduced that can potentially solve the issue. As the name tells, RBC‐PDT harnesses erythrocytes, an O₂ transporter, as a carrier for photosensitizers. Because photosensitizers are adjacent to a carry‐on O₂ source, RBC‐PDT can efficiently produce ¹O₂ even under low oxygen conditions. The treatment also benefits from the long circulation of RBCs, which ensures a high intraluminal concentration of photosensitizers during PDT and hence maximizes damage to tumor blood vessels. When tested in U87MG subcutaneous tumor models, RBC‐PDT shows impressive tumor suppression (76.7%) that is attributable to the codelivery of O₂ and photosensitizers. Overall, RBC‐PDT is expected to find wide applications in modern oncology.     

血红素铁改善缺铁性贫血效果观察

目的 了解血红素铁对缺铁性贫血的影响.方法 将符合贫血诊断的女性108人随机分为血红素铁组和对照组,并分别给予血红素铁和安慰剂,连续服用45 d,服用开始前和服用结束时对受试者进行膳食营养调查、体格检查和血液生化指标的检测并进行统计学分析.结果 血红素铁组血红蛋白的含量由试验前的(106.43±10.48) g/L上升到(117.34±10.25)g/L,平均升高了10.91 g/L(服用前后配对t检验,P＜0.05,服用后与对照组t检验,P＜0.05);红细胞游离原卟啉的含量由(942.15±96.34)μg/L下降为(820.53±109.95)μg/L(服用前后配对t检验,P＜0.05,服用后与对照组t检验,P＜0.05);试验组血清铁蛋白的含量由试验前的(25.19±6.71) ng/ml上升到(25.40±6.69) ng/ml,(服用前后配对t检验,P＞0.05).结论 血红素铁对缺铁性贫血具有一定的改善作用.并对受试者健康无不良影响.     

幼年特发性关节炎全身型血清铁蛋白的水平变化及临床意义

目的探讨血清铁蛋白（serumferritin,SF）在幼年特发性关节炎全身型（systemonset juvenileidiopathic ar-thritis,SoJIA）的水平变化及临床意义。方法采用化学发光法检测SoJIA组患儿（n=30）在治疗前活动期和治疗后病情缓解期SF水平的变化;同时检测感染性疾病组（n=30）、肿瘤组（n=30）及其他结缔组织病组（n=30）患儿的SF水平。结果 SoJIA组、感染性疾病组、肿瘤组及其他结缔组织病组患儿的血清SF水均升高;SoJIA组活动期血清SF水平显著高于其他3组（均P〈0.01）;SoJIA组活动期SF水平明显高于缓解期（P〈0.01）。结论 SF是诊断SoJIA有价值的实验室指标,并可为病情活动期及疗效观察提供依据。     

Ferritin–Polymer Conjugates: Grafting Chemistry and Integration into Nanoscale Assemblies

Controlled free radical polymerization chemistry is used to graft polymer chains to the corona of horse spleen ferritin (HSF) nanocages. Specifically, poly(methacryloyloxyethyl phosphorylcholine) (polyMPC) and poly(PEG methacrylate) (polyPEGMA) chains are grafted onto the nanocages by atom transfer radical polymerization (ATRP), in which the molecular weight of the polymer grafts is controlled by the monomer‐to‐initiator feed ratio. PolyMPC and polyPEGMA‐grafted ferritin show a generally suppressed inclusion into diblock copolymer films relative to native ferritin, and the polymer coating is seen to mask the ferritin nanocages from antibody recognition. The solubility of polyPEGMA‐coated ferritin in organic solvents enables its processing with polystyrene‐block‐poly(ethylene oxide) copolymers, and selective integration into the PEO domains of microphase‐separated copolymer structures.     

Functional iron deficiency in hemodialysis patients with high ferritin

Although functional iron deficiency (FID) may be present in hemodialysis (HD) patients with high serum ferritin levels (>800 ng/mL), current protocols often preclude the use of intravenous (IV) iron in these patients. However, it has not been demonstrated that iron supplementation during erythropoietin therapy is ineffective or unsafe in increasing hemoglobin (Hb) levels in patients with high serum ferritin. This report describes the hematologic efficacy and safety of ferric gluconate (FG) therapy in patients with serum ferritin >800 ng/mL. A retrospective analysis was performed on HD patients at a single California dialysis center from January 1 to December 31, 2003. Patients classified as having high ferritin levels (serum ferritin >800 ng/mL on at least 66% of routine monthly measurements and transferrin saturation [TSAT] <25% on at least 1 occasion) were stratified as follows: patients in Group I were suspected of having FID and received FG > or =250 mg IV over a 3-month period when Hb was <11 g/dL, and patients in Group II were thought not to have FID and received <250 mg FG over a 3-month period. Both groups received standard recombinant human erythropoietin therapy as per the unit's protocol. Of 496 patients, 95 exhibited high ferritin and of these, 39 patients had sufficient data for analysis. Group I patients (n=14) showed a significant increase in Hb levels compared with Group II (n=25). There was no increase in ferritin levels in response to iron administration. No significant differences in hospitalizations or infections were observed between groups. Hemodialysis patients with high ferritin levels may have FID, and IV iron therapy safely improves FID in some patients. A larger randomized trial examining the optimal management of iron administration in HD patients with high ferritin levels is warranted.