Photothermal therapy (PTT) is a promising clinical antitumor strategy. However, local hyperthermia inevitably induces heat damage to adjacent normal tissues, while alternative mild-temperature therapy (MPTT, T < 45 °C) is also inefficient due to the overexpressed hyperthermia-induced heat shock proteins (HSPs) by cancer cells. Therefore, developing PTT strategies with minimizing damage to healthy tissues with improved cellular temperature sensitivity is extremely valuable for clinical application. Herein, we proposed the strategy of disrupting the intracellular redox environment via destroying the ROS-defending systems to promote MPTT. The gold(III) porphyrin-Fe3+-tannic acid nanocomplexes (AuTPP@TA-Fe NPs) were achieved via interfacial cohesion and supramolecular assembly of bioadhesive species, which could trigger the Fenton reaction to produce ·OH radicals and downregulation of reductive TrxR enzyme and mitochondrial chaperone protein Hsp60. The aggravation of oxides and the inactivation of Hsp60 provide favorable pathways for impeding the heat shock-induced self-repair mechanism of cancer cells, which strengthens AuTPP@TA-Fe NPs mediated MPTT.

The invention relates to a preparation method for a lysosomal membrane coated nanoparticle. Under the function of the driving of macrophages, an active lysosomal membrane coated nanoparticle is synthesized. Specifically, the preparation method comprises the following steps of: firstly, activating the macrophages by lipopolysaccharides, stimulating the secretion of lysosomal related proteases in the macrophages, and enhancing the enzymatic activity of the lysosomal related proteases; then, utilizing the phagocytic ability of the macrophages to jointly incubate the prepared nanoparticle and themacrophages to enable the macrophages to carry out phagocytosis on the nanoparticle, and carrying out internalization on the nanoparticle in macrophage lysosome; and finally, utilizing a lysosome extraction kit to extract the lysosome to obtain the lysosomal membrane coated nanoparticle. Compared with a preparation method for a traditional lipid membrane coated nanoparticle, on one hand, the preparation method disclosed by the invention is simple, and does not need to consider damage caused for the membrane by pressure or electric shock. On the other hand, the macrophages are taken as drivingforce, and the prepared lysosomal membrane coated nanoparticle keeps the activity of hydrolase in the lysosome.

肿瘤微环境在肿瘤的发生和发展过程中发挥着至关重要的作用,越来越多的研究致力于开发可调节或响应肿瘤微环境的药物,但它们存在靶向性差、性质不稳定、生物利用度低等问题,难以最大程度发挥治疗效果.随着纳米技术的飞速发展,基于肿瘤微环境设计的纳米药物在抗肿瘤治疗中受到了广泛关注:一方面可通过响应肿瘤微环境,赋予纳米药物更多功能(如药物可控释放、肿瘤组织深部渗透等),提升抗肿瘤疗效;另一方面可通过调节肿瘤微环境,破坏肿瘤细胞生长所需的"土壤"(如肿瘤基质细胞、肿瘤细胞外基质等),高效抑制肿瘤生长.本文综述了近年来基于肿瘤微环境构建纳米药物的思路及其应用,并对存在的问题进行系统探讨,以期为纳米药物的设计提供指导性参考.

凭借独特的尺寸效应和理化性质,纳微颗粒在生物医药领域的应用日益广泛,其与细胞的相互作用也备受关注,对其进行定量测量和机制研究愈发重要.目前,原子力显微镜(atomic force microscopy,AFM)由于具有高灵敏度(皮牛级)、高分辨率(纳米级)以及在生理环境中可进行实时检测等优势成为检测颗粒与细胞相互作用的重要工具.利用AFM检测颗粒与细胞相互作用,有助于确定作用过程中的重要参数,解释颗粒在药物递送、免疫响应和细胞力学等应用方面深层次的机制.本文中,笔者就原子力显微镜检测颗粒与细胞相互作用及其应用进行系统的综述,并对其未来的发展方向进行展望.

We describe here the synthesis and cell-selective delivery of a cationic Pt(IV)-backboned prodrug-like polymer P(DSP-DAEP). P(DSP-DAEP) features excellent aqueous solubility, unusually high (44.5%) drug loading, can be rapidly reduced to release the active cisplatin, and is more potent than its small molecular Pt(IV) precursor DSP. P(DSP-DAEP) can be formulated with an oppositely charged methoxyl poly(ethylene glycol)-block-poly(L-phosphotyrosine) (mPEG-b-PpY) to afford a polyion micelle (Pt-PIC) by taking advantage of polyelectrolyte coacervation. Preliminary in vitro cellular uptake and cytotoxicity assays indicate that Pt-PIC exhibits receptor (surface alkaline phosphatase)-dependent uptake and cytotoxicity. Overall, our results suggest a new approach to the improved therapeutic index of platinum-based anticancer drugs via cell-selective delivery.

Synthetic progress in wet chemistry synthesis of plasmonic nanoparticles provides a rational route to engineer their sizes and shapes, formulating so-called plasmonic periodic table. Control over self-assembly of these plasmonic atoms allows for fabrication of unique SERS substrates which are soft and elastic enabling direct identification of chemicals sitting on topologically complex surfaces or satellite SERS particles. Satellite SERS particle can be designed and fabricated into multifunctional particles by utilizing multicomponent hybrid nanostructures, in particular involving a combination of magnetic and plasmonic properties. In this PhD work, I’ve focused on designing a bifunctional metal-metal oxide Fe3O4@AuNPs@Ag particle. The bifunctional particles were then synthesized, applied and enhanced for biosensing in microfluidic platform developed in CSIRO microfluidic lab to improve the assay time and binding specificity. With extensive tuning on plasmonic particle size, fluid flow and mixing time, these particles were demonstrated to achieve low limit of detection of rabbit Immunoglobulin G antibody with improved binding specificity compared to conventional non-microfluidic immunoassay. In another application, I’ve used this bifunctional particle for mechanical sensing. To do this, I’ve grown gold nanowires (AuNWs) on Fe3O4 particle. After the growth, this particle became a three dimensional conductive percolation network which can be useful in pressure sensing applications. I have also explored the ability of using this particle in fabrication of sensors for other mechanical sensing application such as strain, wind and magnetic field sensing.

纳米颗粒作为抗肿瘤药物的理想载体，正受到越来越多的关注。近年来的研究发现，抗肿瘤纳米载药颗粒的粒径、形状、表面电荷等理化因素很大程度上影响细胞对载体的摄取及响应能力，进而影响药效的发挥。在微观细胞层面上理解载体理化性质的影响，可以有针对性地设计纳米药物输送体系，使药物获得理想的血液循环时间、肿瘤靶向能力和抗肿瘤效果。就目前的研究进展而言，纳米颗粒的功能特性、其他性质与生物学效应及抗肿瘤效果的相关研究依然存在一定的空白，并且抗肿瘤药物载体的设计也需要新的思路与方法。

BACKGROUND: The non-specific distribution of anticancer drugs in vivo may cause serious side effects and low bioavailability. Drug carriers with the active targeting abilities can solve these problems. OBJECTIVE: To review the recent studies on carrier preparation for anticancer drug delivery and summarize different types of active targeting strategies for drug carrier. METHODS: A computer-based online search was performed for articles published from 2004 to 2011 in Web of Knowledge database with the English key words that closely related to various active targeting strategies, such as "tumor, drug carrier, active targeting". Totally 58 articles were retrieved, and finally 26 of them met the requirement. RESULTS AND CONCLUSION: Active targeting strategy is the first problem need to consider and the most important part in designing anticancer drug carriers. It contributes to the actual effect of drug delivery and bioavailability of drug. Drug carriers with various active targeting abilities can carry antitumor drugs to tumor sites and significantly reduced the non-specific distribution of drugs in vivo in order to decrease the side effects and enhanced bioavailability.

Apoferritin-encapsulated Pt nanoparticles (AFt-Pt) were bio-mimetically prepared by an in situ reduction method in the unique 8 nm spherical cage of apoferritin. The average size of AFt-Pt was 4.3 +/- 0.9 nm. The spherical structure of apoferritin remained intact after loading Pt particles in its cavity. Apoferritin coating increased the amount of Pt internalized in HepG2 cells by about three times via receptor-mediated endocytosis. AFt-Pt showed greatly improved biocompatibility compared with polyvinylpyrrolidone stabilized Pt nanoparticles (PVP-Pt). More than 80% of cells survived after treatment with 100 mM AFt-Pt for 48 h. By camouflaging the particles with a protein corona, apoferritin conferred a cell-recognizable identity to the particles, which strikingly ameliorated the bio-effects of the nanoparticles.

The unicellular green alga Haematococcus pluvialis accumulates a high-valuable astaxanthin under stress conditions. Beta-carotene ketolase (BKT), a key enzyme in astaxanthin biosynthesis in H. pluvialis, catalyzes the conversion of β-carotene to canthaxanthin and zeaxanthin to astaxanthin. Electrophoresis mobility shift assay (EMSA) was used in H. pluvialis to identify transcription factor binding sites within a 309bp promoter region (-617/-309) of beta-carotene ketolase gene and a 59bp sequence between -396 and -338bp was found to have a specific binding activity to the nuclear protein. Sequence analysis revealed that this important functional region contains neither TATA nor CAAT box but a G-box involved in the responsiveness of light, anaerobiosis, p-coumaric acid and hormone.