Intercalated 2D nanoclay for emerging drug delivery in cancer therapy

Natural two-dimensional (2D) kaolinite nanoclay has been incorporated into an emerging drug delivery system.The basal spacing of the kaolinite nanoclay was expanded from 0.72 to 4.16 nm through the intercalation of various organic guest species of different chain lengths,which can increase the efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX).Original kaolinite (Kaolin) and the Kaolin intercalation compounds exhibited a high level of biocompatibility and very low toxicity towards cells of pancreatic cancer,gastric cancer,prostate cancer,breast cancer,colorectal cancer,esophageal cancer,and differentiated thyroid cancer.However,lung cancer and hepatocellular cancer cells need more strict compositional,structural,and morphological modulations for drug delivery carriers.DOX-Kaolin and the DOX-Kaolin intercalation compounds showed dramatically faster drug release in moderately acidic solution than in neutral condition,and exhibited enhanced therapeutic effects against ten model cancer cell cultures in a dose-dependent manner.The use of 2D nanoclay materials for a novel drug delivery system could feasibly pave a way towards high-performance nanotherapeutics,with superior antitumor efficacy and significantly reduced side effects.     

Multifunctional nanoassemblies of block copolymers for future cancer therapy

Abstract

Nanoassemblies from amphiphilic block copolymers are promising nanomedicine platforms for cancer diagnosis and therapy due to their relatively small size, high loading capacity of drugs, controlled drug release, in vivo stability and prolonged blood circulation. Recent clinical trials with self-assembled polymeric micelles incorporating anticancer drugs have shown improved antitumor activity and decreased side effects encouraging the further development of nanoassemblies for drug delivery. This review summarizes recent approaches considering stimuli-responsive, multifunctionality and more advanced architectures, such as vesicles or worm-like micelles, for tumor-specific drug and gene delivery.     

Multifunctional nanoassemblies of block copolymers for future cancer therapy

Nanoassemblies from amphiphilic block copolymers are promising nanomedicine platforms for cancer diagnosis and therapy due to their relatively small size, high loading capacity of drugs, controlled drug release, in vivo stability and prolonged blood circulation. Recent clinical trials with self-assembled polymeric micelles incorporating anticancer drugs have shown improved antitumor activity and decreased side effects encouraging the further development of nanoassemblies for drug delivery. This review summarizes recent approaches considering stimuli-responsive, multifunctionality and more advanced architectures, such as vesicles or worm-like micelles, for tumor-specific drug and gene delivery.     

纳米级碳酸钙粉末材料的制备研究

利用CO2-Ca(OH)2-H2O体系制备了纳米级碳酸钙粒子,探讨了无添加剂制备过程中CO2流量对粒子大小和分散性能的影响.碳化前,在体系中引入了能与Ca2 生成沉淀的化合物,研究了硅酸钠、草酸钾、硼酸等对促进碳酸钙成核的效果.利用TEM、XRD和粒度分布测试对产品进行了表征.结果表明:CO2的最佳流量为6～7mL/s.添加草酸钾后制得的产品,具有粒度均匀、分散性好等优点,粒子的平均粒径为60～70 nm.     

石墨烯纳米材料在药物释放和基因传递中的应用

石墨烯纳米材料由于其独特的结构和优良的机械、光学和电学性能,已经在物理、化学和材料科学等领域广泛应用。最新研究表明其特殊的属性可应用在生物医学领域的,综述了石墨烯纳米材料在生物医学领域如药物释放和基因传递中的应用,最后指出了石墨烯纳米材料在生物医学领域应用中目前存在的问题。     

Assembly of nano-superstructural aragonite CaCO3 by living bio-membrane

Biomimetic living templates, mung bean sprouts (MBS), were employed to control the crystallisation of calcium carbonate. Metastable aragonite superstructure can be readily generated in normal conditions. Some interesting morphologies including elaborate piny dendritic, flowerlike and rods were also prepared using citric acid, nitrilotriacetic acid and ethylenediaminetetraacetic acid as cooperation modifiers in the mineralisation process, under the conditions of 0.01% of crystal modifier and ambient temperature. These morphologies were assembled by some elaborate substructures, similar to nanowire and featherlike crystals. The products were characterised by SEM, XRD and FTIR, respectively. The results indicated that the formation of aragonite polymorph of calcium carbonate was favoured in this system. A probable mechanism was proposed.     

Synthesis of protein nano-conjugates for cancer therapy

A eukaryotic cell contains thousands of proteins that regulate its cellular function; delivering functional proteins into cells to rectify cellular functions holds great promise for treatment of various diseases, especially cancers. In this context, ribonuclease (RNase), an enzyme that breaks down ribonucleic acid (RNA), has great potential for cancer therapy. However, its therapeutic application is hampered by poor intracellular delivery efficiency and inhibition by ubiquitous intracellular RNase inhibitors. In this work, by designing and synthesizing RNase nano-conjugates by in situ atom transfer radical polymerization (ATRP), we demonstrate a simple solution to address both challenges. Compared with native RNase, nano-conjugates exhibit significantly enhanced intracellular delivery efficiency, inhibitor resistance, and a near five-fold increase in cytotoxicity. This work provides a novel platform for delivery of therapeutic proteins for cancer therapy and other applications.     

Exploration of Antigen Induced CaCO3 Nanoparticles for Therapeutic Vaccine

Therapeutic vaccines possess particular advantages and show promising potential to combat burdening diseases, such as acquired immunodeficiency syndrome, hepatitis, and even cancers. An efficient therapeutic vaccine would strengthen the immune system and eventually eliminate target cells through cytotoxic T lymphocytes (CTLs). Unfortunately, insufficient efficacy in triggering such an adaptive immune response is a problem that remains unsolved. To achieve efficient cellular immunity, antigen‐presenting cells must capture and further cross‐present disease‐associated antigens to CD8 T cells via major histocompatibility complex I molecules. Here, a biomimetic strategy is developed to fabricate hierarchical ovalbumin@CaCO₃ nanoparticles (OVA@NP, ≈500 nm) under the templating effect of antigen OVA. Taking advantage of the unique physicochemical properties of crystalline vaterite, cluster structure, and high loading, OVA@NP can efficiently ferry cargo antigen to dendritic cells and blast lysosomes for antigen escape to the cytoplasm. In addition, the first evidence that the physical stress from generated CO₂ induces autophagy through the LC3/Beclin 1 pathways is presented. These outcomes cooperatively promote antigen cross‐presentation, elicit CD8 T cell proliferation, ignite a potent and specific CTL response, and finally achieve prominent tumor therapy effects.     

醇钙法和醇-水二元溶剂法制备亚稳态球霰石相CaCO3

提出了醇钙法概念, 并采用该方法制备了亚稳态球霰石相CaCO₃, 即利用CaCl₂溶解于乙醇形成的络合物与Na₂CO₃水溶液之间的反应制备球霰石相CaCO₃。主要研究了陈化时间和反应温度对产物晶相组成和颗粒形貌的影响, 并与相同条件下传统醇-水二元溶剂法制备CaCO₃进行了对比。X射线衍射(XRD)表征结果表明, 两种制备方法得到的产物中球霰石相的含量均随反应时间的延长和反应温度的升高而降低, 但是醇钙法得到的球霰石的含量远大于醇-水二元溶剂法, 且醇钙法得到的球霰石的稳定性也远优于醇-水二元溶剂法。SEM观察结果表明, 两种制备方法得到的产物中的球霰石和方解石颗粒均为其典型形貌, 即球状和菱方状。     

碳化法制备超细碳酸钙反应中凝胶现象的研究

为了研究制备超细碳酸钙过程中凝胶现象对反应过程及产物性能的影响,本文中以碳化法制备超细碳酸钙中的凝胶现象为例,研究了不同工艺参数(温度、石灰乳浓度、碳化气体流量、添加剂)对凝胶现象的影响,探讨了凝胶产生的微观原因,并提出了加入适当成核添加剂以避免凝胶产生的新方法。研究结果表明,避免凝胶出现或减轻凝胶现象的主要方法是在保持产品粒径达到要求的前提下控制反应温度在一定范围内,CO2的气体流量不能过大,石灰乳液浓度不能过高。选择适当的能产生微晶的添加剂来优化反应进程,能够与体系中的反应物作用产生微晶的物质,避免凝胶的发生。     

Multifunctional nanoparticle systems for combined chemo- and photothermal cancer therapy

Hyperthermia has long been considered as an adjuvant therapy for treating various diseases. Cancer treatment exploiting hyperthermia shows great clinical potential for a wide range of tumors. Importantly, the efficacy of hyperthermal therapy has recently been enhanced by the development of functional nanomaterials. The unique physicochemical properties of nanomaterials afford the specific localization of hyperthermia to primary tumors and early-stage cancers. In particular, due to their high rate of light-to-heat conversion and their capacity to be activated by tissue-penetrating electromagnetic radiation, near-infrared (NIR) light-absorbing plasmonic nanomaterials have attracted considerable attention as candidates for noninvasive photothermal therapy. The purpose of this article is to provide a overview on the current development in multifunctional nanomaterials capable of combined hyperthermia-chemotherapy delivery.     

Synthesis of biomolecule-modified mesoporous silica nanoparticles for targeted hydrophobic drug delivery to cancer cells

Synthetic methodologies integrating hydrophobic drug delivery and biomolecular targeting with mesoporous silica nanoparticles are described. Transferrin and cyclic-RGD peptides are covalently attached to the nanoparticles utilizing different techniques and provide selectivity between primary and metastatic cancer cells. The increase in cellular uptake of the targeted particles is examined using fluorescence microscopy and flow cytometry. Transferrin-modified silica nanoparticles display enhancement in particle uptake by Panc-1 cancer cells over that of normal HFF cells. The endocytotic pathway for these particles is further investigated through plasmid transfection of the transferrin receptor into the normal HFF cell line, which results in an increase in particle endocytosis as compared to unmodified HFF cells. By designing and attaching a synthetic cyclic-RGD, selectivity between primary cancer cells (BT-549) and metastatic cancer cells (MDA-MB 435) is achieved with enhanced particle uptake by the metastatic cancer cell line. Incorporation of the hydrophobic drug Camptothecin into these two types of biomolecular-targeted nanoparticles causes an increase in mortality of the targeted cancer cells compared to that caused by both the free drug and nontargeted particles. These results demonstrate successful biomolecular-targeted hydrophobic drug delivery carriers that selectively target specific cancer cells and result in enhanced drug delivery and cell mortality.     

纳米碳酸钙表面处理对PVC／CaCO3性能的影响

采用硬脂酸与硅烷偶联剂表面处理、PMMA水解接枝处理等方法对CaCO3进行表面改性,考察改性纳米钙对PVC／CaCO3复合材料力学性能的影响。     

Soluplus/TPGS mixed micelles for dioscin delivery in cancer therapy

Background: Dioscin has shown cytotoxicity against cancer cells, but its poor solubility and stability have limited its clinical application. In this study, we designed mixed micelles composed of TPGS and Soluplus^® copolymers entrapping the poorly soluble anticancer drug dioscin.

Method: In order to improve the aqueous solubility and bioactivity of dioscin, TPGS/Soluplus^® mixed micelles with an optimal ratio were prepared using a thin-film hydration method, and their physicochemical properties were characterized. Cellular cytotoxicity and uptake of the dioscin-loaded TPGS/Soluplus^® mixed micelles were studied in MCF-7 breast cancer cells and A2780s ovarian cancer cells. The pharmacokinetics of free dioscin and dioscin-loaded TPGS/Soluplus^® mixed micelles was studied in vivo in male Sprague-Dawley rats via a single intravenous injection in the tail vein.

Results: The average size of the optimized mixed micelle was 67.15?nm, with 92.59% drug encapsulation efficiency and 4.63% drug loading efficiency. The in vitro release profile showed that the mixed micelles presented sustained release behavior compared to the anhydrous ethanol solution of dioscin. In vitro cytotoxicity assays were conducted on human cancer cell lines including A2780s ovarian cancer cells and MCF-7 breast cancer cells. The mixed micelles exhibited better antitumor activity compared to free dioscin against all cell lines, which may benefit from the significant increase in the cellular uptake of dioscin from mixed micelles compared to free dioscin. The pharmacokinetic study showed that the mixed micelle formulation achieved a 1.3 times longer mean residual time (MRT) in circulation and a 2.16 times larger area under the plasma concentration–time curve (AUC) than the free dioscin solution.

Conclusion: Our results suggest that the dioscin-loaded mixed micelles developed in this study might be a potential nano drug-delivery system for cancer chemotherapy.     

纳米碳酸钙湿法表面改性的研究

利用季铵型阳离子表面活性剂对纳米碳酸钙进行了湿法表面改性。对湿法改性前后的纳米碳酸钙进行了红外光谱(FTIR)、X射线衍射(XRD)及透射电镜(TEM)分析。采用Zeta电位、分散体系浊度、沉降体积、表观粘度等分析方法对改性前后纳米碳酸钙在水中的界面行为进行评价。另外,通过激光粒度仪对改性前后纳米碳酸钙分散液的粒度分布进行了测定。实验结果表明,经湿法表面改性后,纳米碳酸钙在水中的润湿性及分散性有很大改善。     

PVC/CPE/CaCO_3复合材料熔体的动态流变行为EI北大核心CSCD

以聚氯乙烯(PVC)为基体,采用熔融共混法制备了PVC/氯化聚乙烯(CPE)/碳酸钙(CaCO3)复合材料,对不同CPE含量的PVC/CPE/CaCO_3复合材料的动态流变行为与力学性能进行了研究。结果表明:随着CPE含量的增加,复合材料熔体的储能模量(G′)与损耗模量(G″)先升高后降低,而松弛指数(λ_1)、特征松弛时间(τ_2)则分别呈现减小与增大的趋势,当CPE含量由0phr变为10phr时,复合材料冲击性能提高了约133.5%。通过对复合材料熔体动态流变行为进行分析,可以推测出CPE与CaCO_3颗粒之间逐渐形成部分包覆、全包覆、过包覆的结构模型,从而解释了CPE增韧复合材料的机理。