Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses.     

Surface decoration of magnetic nanoparticles with folate-conjugated poly(N-isopropylacrylamide-co-itaconic acid): A facial synthesis of dual-responsive nanocarrier for targeted delivery of doxorubicin

The aim of study was to develop a novel drug nanocarrier via facile coating of a folate-conjugated dual-responsive copolymer with carboxylic functional groups on the surface of magnetic nanoparticles for the efficient loading and cell-specific targeting of a positively charged anticancer agent. The nanocarrier exhibited many favorable capabilities such as narrow distributed nano-ranged size (～30 nm), high drug loading capacity (～65%), and stimuli-responsive drug release. The results of various cell cytotoxicity studies such as MTT assay, DAPI staining, and flow cytometry concluded that the developed smart nanocarrier paves a way for efficient cancer therapy by the multiple targeting strategies.     

纳米靶向技术在智能释药系统的应用

智能纳米靶向释药载体能对外界环境的温度、pH值、电、磁、化学物质等的刺激信号做出响应，并控制药物按设定目标释放。根据不同机理，纳米靶向技术分生物靶向、理化靶向及复合靶向3种。综述了纳米靶向技术在智能释药系统的最新应用研究进展。随着纳米技术的进一步发展和现有技术的不断完善，纳米载体智能释药系统在实际应用中会大规模采用，为人类战胜疾病作出贡献。     

Development of Drug Delivery Systems Based on Layered Hydroxides for Nanomedicine

Layered hydroxides (LHs) have recently fascinated researchers due to their wide application in various fields. These inorganic nanoparticles, with excellent features as nanocarriers in drug delivery systems, have the potential to play an important role in healthcare. Owing to their outstanding ion-exchange capacity, many organic pharmaceutical drugs have been intercalated into the interlayer galleries of LHs and, consequently, novel nanodrugs or smart drugs may revolutionize in the treatment of diseases. Layered hydroxides, as green nanoreservoirs with sustained drug release and cell targeting properties hold great promise of improving health and prolonging life.     

杂交蛋白氧载体光动力治疗诱导免疫原性细胞死亡的研究

肿瘤细胞发生免疫原性细胞死亡能释放特定的信号分子,从而触发机体产生特异性抗肿瘤免疫应答,对评估肿瘤治疗方法的长期疗效具有重要意义。该研究以血红蛋白(Hb)和人血清白蛋白(HSA)为材料,采用二硫键共价偶联的方法构建了包载光敏剂二氢卟吩 e6(Ce6)的杂交蛋白氧载体(C@Hb/HSA),并考察了 C@Hb/HSA 对结肠癌细胞(CT26.WT)的光动力治疗效果和诱导免疫原性细胞死亡的情况。结果显示,在激光照射下,低剂量的 C@Hb/HSA 能显著提升CT26.WT 细胞内的活性氧水平,使其细胞存活率降低至(17.8±5.5)%。同时,基于 C@Hb/HSA 的光动力治疗能有效增加细胞表面钙网蛋白的暴露,从而增强 CT26.WT 细胞的免疫原性,促进树突状细胞的成熟。     

脂肪酸糖醇酯制备脂质纳米载体对姜黄素的包裹及释放性能的研究

采用溶解-超声法,以质量比90∶10的肉豆蔻酸赤藓糖醇单酯和月桂酸乙二醇单酯复配物为原料制备了脂质纳米载体,并对疏水性药物姜黄素进行包载,采用扫描电子显微镜和原子力显微镜对脂质纳米载体进行形态学表征,然后利用体外模拟消化系统探究包载姜黄素的脂质纳米载体进入消化道的释放与分解情况。结果表明:得到了粒径分布均匀、大小分别为250.63 nm及265.42nm的空脂质纳米载体及包载姜黄素的脂质纳米载体,包载率达到94.60%;通过不同温度的体外释放实验,发现在37、42℃下姜黄素释放率快速达到98%以上,证明脂质纳米载体对37℃以上的温度具有温敏性;在胃部消化过程中包载姜黄素的脂质纳米载体发生了载体溶解,姜黄素释放率快速上升达到97.81%并趋于平稳;而在胰脂酶、胆汁盐及pH的共同影响下,姜黄素在进入模拟的肠道环境后发生分解,其含量随消化进程快速下降,30 min便分解殆尽。     

Design of nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleic acid drugs: learning from virus

There are many challenges in developing efficient and target specific delivery systems of small molecule and nucleic acid drugs. Cell membrane presents one of the major barriers for the penetration of hydrophilic macromolecules across the plasma membrane. Nanocarriers have been designed to enhance their cellular uptake via endocytosis but following their cellular uptake, endosomal escape is the rate limiting step which restricts the value associated with the enhanced uptake by nanocarriers. Viruses are an excellent model for efficient cytosolic delivery by nanocarriers. Viruses exploit intracellular cues to release the genome to cytosol. In this review, we first discuss different endocytic uptake pathways and endosomal escape mechanisms. We then summarize the existing tools for studying the intracellular trafficking of nanocarriers. Finally, we highlight the important design elements of recent virus-based nanocarriers for efficient cellular uptake and endosomal escape.     

Mesoporous Silica Nanoparticles (MCM-41) Coated PEGylated Chitosan as a pH-Responsive Nanocarrier for Triggered Release of Erythromycin

A pH-responsive drug delivery system based on core shell structure of mesoporous silica nanoparticle (MSN) and chitosan-PEG copolymer was prepared and characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscope (SEM), and high-resolution transmission microscope (HR-TEM) techniques. In order to improve compatibility MSN and drug, mesoporous nanosilica was modified by 3-aminopropyl triethoxysilane. The release of erythromycin (a macrolide antibiotic) as a model drug was investigated in two pHs, 7.4 and 5.5.