Nanomedicine: Engineering Nanocomposite Materials for Cancer Therapy (Small 21/2010)

Cancer accounted for 13% of all deaths worldwide in 2005. Although early detection is critical for the successful treatment of many cancers, there are sensitivity limitations associated with current detection methodologies. Furthermore, many traditional anticancer drug treatments exhibit limited efficacy and cause high morbidity. The unique physical properties of nanoscale materials can be utilized to produce novel and effective sensors for cancer diagnosis, agents for tumor imaging, and therapeutics for cancer treatment. Functionalizing inorganic nanoparticles with biocompatible polymers and natural or rationally designed biomolecules offers a route towards engineering responsive and multifunctional composite systems. Although only a few such innovations have reached human clinical trial to date, nanocomposite materials based on functionalized metal and semiconductor nanoparticles promise to transform the way cancer is diagnosed and treated. This review summarizes the current state‐of‐the‐art in the development of inorganic nanocomposites for cancer‐related applications.     

Nanoelectromechanical Chip (NELMEC) Combination of Nanoelectronics and Microfluidics to Diagnose Epithelial and Mesenchymal Circulating Tumor Cells from Leukocytes

An integrated nano‐electromechanical chip (NELMEC) has been developed for the label‐free distinguishing of both epithelial and mesenchymal circulating tumor cells (ECTCs and MCTCs, respectively) from white blood cells (WBCs). This nanoelectronic microfluidic chip fabricated by silicon micromachining can trap large single cells (>12 µm) at the opening of the analysis microchannel arrays. The nature of the captured cells is detected using silicon nanograss (SiNG) electrodes patterned at the entrance of the channels. There is an observable difference between the membrane capacitance of the ECTCs and MCTCs and that of WBCs (measured using SiNG electrodes), which is the key indication for our diagnosis. The NELMEC chip not only solves the problem of the size overlap between CTCs and WBCs but also detects MCTCs without the need for any markers or tagging processes, which has been an important problem in previously reported CTC detection systems. The great conductivity of the gold‐coated SiNG nanocontacts as well as their safe penetration into the membrane of captured cells, facilitate a precise and direct signal extraction to distinguish the type of captured cell. The results achieved from epithelial (MCF‐7) and mesenchymal (MDA‐MB231) breast cancer cells circulated in unprocessed blood suggest the significant applications for these diagnostic abilities of NELMEC.     

Diameters of single-walled CNTs (SWCNTs) and related nanochemistry and nanobiology

We reviewed and examined recent progresses related to the nanochemistry and nanobiology of signal-walled carbon nanotubes (SWCNTs), focusing on the diameters of SWCNTs and how the diameters affect the interactions of SWCNT with protein and DNA, which underlay more complex biological responses. The diameters of SWCNTs are closely related to the electronic structure and surface chemistry of SWCNTs, and subsequently affect the interaction of SWCNTs with membrane, protein, and DNA. The surfaces of SWCNT with smaller diameters are more polar, and these with large diameters are more hydrophobic. The preference of SWCNT to interact with Trp/Phe/Met residues indicates it is possible that SWCNT may interfere with normal protein-protein interactions. SWCNT-DNA interactions often change DNA conformation. Besides the promising future of using SWCNTs as delivering nanomaterial, thermal therapy, and other biological applications, we should thoroughly examine the possible effects of carbon nanotube on interrupting normal protein-protein interaction network and other genetic effects at the cellular level.     

Paclitaxel-loaded hollow-poly(4-vinylpyridine) nanoparticles enhance drug chemotherapeutic efficacy in lung and breast cancer cell lines

Paclitaxel (PTX),one of the most effective cytotoxins for the treatment of breast and lung cancer,is limited by its severe side effects and low tumor selectivity.In this work,hollow-poly(4-vinylpyridine) (hollow-p4VP) nanoparticles (NPs) have been used for the first time to generate PTX@p4VP NPs,employing a novel technique in which a gold core in the center of the NP is further oxidized to produce the hollow structure into which PTX molecules can be incorporated.The hollow-p4VP NPs exhibit good physicochemical properties and displayed excellent biocompatibility when tested on blood (no hemolysis) and cell cultures (no cytotoxicity).Interestingly,PTX@p4VP NPs significantly increased PTX cytotoxicity in human lung (A-549) and breast (MCF-7) cancer cells with a significant reduction of PTX IC50 (from 5.9 to 3.6 nM in A-549 and from 13.75 to 4.71 nM in MCF-7).In addition,PTX@p4VP caused a decrease in volume of A-549 and MCF-7 multicellular tumor spheroids (MTS),an in vitro system that mimics in vivo tumors,in comparison to free PTX.This increased antitumoral activity is accompanied by efficient cell internalization and increased apoptosis,especially in lung cancer MTS.Our results offer the first evidence that hollowp4VP NPs can improve the antitumoral activity of PTX.This system can be used as a new nanoplatform to overcome the limitations of current breast and lung cancer treatments.     

A Nitric Oxide (NO) Nanoreporter for Noninvasive Real-Time Imaging of Macrophage Immunotherapy

Macrophage-centered therapeutic approaches that rely on immune modulation of tumor associated macrophages (TAMs) from a pro-tumorigenic phenotype (M2) to an anti-tumorigenic phenotype (M1) have facilitated a paradigm shift in macrophage immunotherapy. However, limited clinical success has been achieved due to the low response rates observed in different types of cancers. The ability to measure immune response in real time is critical in order to differentiate responders from non-responders; however, there are currently no platforms to monitor real-time macrophage immunotherapy response. Hence, there is an immediate need to develop imaging techniques that can longitudinally monitor macrophage immunotherapy response. Nitric oxide (NO) produced as a result of activation of macrophages to an anti-tumorigenic state is considered as a hallmark of M1 and can be a direct indication of response. In this study, a NO nanoreporter (NO-NR) is reported that enables real-time monitoring of macrophage immunotherapy drugs in vitro and in vivo. Furthermore, it is observed that sustained inhibition of colony stimulating factor 1 receptor (CSF1R) using a CSF1R inhibitor–NO-NR system leads to enhanced efficacy and better imaging signal. In conclusion, a first-of-its-kind NO nanoreporter tool is reported that can be used as an activatable imaging agent to monitor macrophage immunotherapy response in real time.     

Efficient Gene Therapy of Pancreatic Cancer via a Peptide Nucleic Acid (PNA)‐Loaded Layered Double Hydroxides (LDH) Nanoplatform

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignant tumors with extremely poor prognosis due to the later stage diagnosis when surgical resection is no longer applicable. Alternatively, the traditional gene therapy which drives pancreatic cancer cells into an inactive state and inhibiting the proliferation and metastasis, presents potentials to safely inhibit pancreatic cancer progression, but unfortunately has received limited success to date. Here, an efficient gene therapy of pancreatic cancer is shown via a peptide nucleic acid (PNA)‐loaded layered double hydroxides (LDHs) nanoplatform. Compared with the traditional DNA‐ or RNA‐based gene therapies, the gene therapy using PNA features great advantages in recognizing and hybridizing with the target mutant sequences to form PNA–DNA hybrids with significantly enhanced stability due to the absence of electrostatic repulsion, and the constrained flexibility of the polyamide backbone. Moreover, ultrasmall LDHs are engineered to load PNA and the obtained PNA‐loaded LDH platform (LDHs/PNA) is capable of efficiently and selectively targeting the intranuclear mutant sequences thanks to the proton sponge effect. Treatments with LDHs/PNA demonstrate markedly inhibited growth of pancreatic cancer xenografts via a cancer cell proliferation suppression mechanism. The results demonstrate the great potentials of LDHs/PNA as a highly promising gene therapy agent for PDAC.     

Fabrication of ultrathin Zn(OH)2 nanosheets as drug carriers

Ultrathin two-dimensional (2D) porous Zn(OH)2 nanosheets (PNs) were fabricated by means of one-dimensional Cu nanowires as backbones.The PNs have thickness of approximately 3.8 nm and pore size of 4-10 nm.To form "smart" porous nanosheets,DNA aptamers were covalently conjugated to the surface of PNs.These ultrathin nanosheets show good biocompatibility,efficient cellular uptake,and promising pH-stimulated drug release.     

Dy0.6Tb0.3Pr0.1(Fe0.95Mn0.05)x取向晶体的结构与磁致伸缩

采用Ｃｚｏｃｈｒａｌｓｋｉ方法生长了Ｄｙ０．６Ｔｂ０．３Ｐｒ０．１（Ｆｅ０．９５Ｍｎ０．０５）ｘ（１．８５≤ｘ≤１．９５）取向合金。所有合金主相为立方Ｌａｖｅｓ相结构,择优取向不完整择优取向的方向与Ｘ的大小有关。研究了沿着这些样品的生长方向的磁致伸缩性能以及磁致伸缩性能与压力之间的关系。     

La0.5Y0.5Ni4.8Mn0.1Al0.1和La0.5Y0.5Ni4.8Al0.2合金的储氢性能研究

针对两种新型稀土型储氢合金La0.5Y0.5Ni4.8Mn0.1Al0.1和La0.5Y0.5Ni4.8Al0.2的储氢特性进行研究分析。实验表明,相同温度下,La0.5Y0.5Ni4.8Mn0.1Al0.1和La0.5Y0.5Ni4.8Al0.2合金的PCT曲线基本重合,且都具有优良的吸氢动力学性能;相比之下,后者的滞后系数要小于前者,吸氢量较大,吸氢速率也较快,故其储氢性能较优。300次吸放氢循环实验结果表明,La0.5Y0.5Ni4.8Al0.2合金的吸氢动力学性能虽然略有下降,但抗粉化性能较好。     

Intelligent anticancer drug delivery performances of two poly(N-isopropylacrylamide)-based magnetite nanohydrogels

This article evaluates the anticancer drug delivery performances of two nanohydrogels composed of poly(N-isopropylacrylamide-co-itaconic anhydride) [P(NIPAAm-co-IA)], poly(ethylene glycol) (PEG), and Fe₃O₄ nanoparticles. For this purpose, the magnetite nanohydrogels (MNHGs) were loaded with doxorubicin hydrochloride (DOX) as a universal anticancer drug. The morphologies and magnetic properties of the DOX-loaded MNHGs were investigated using transmission electron microscopy (TEM) and vibrating–sample magnetometer (VSM), respectively. The sizes and zeta potentials (ξ) of the MNHGs and their corresponding DOX-loaded nanosystems were also investigated. The DOX-loaded MNHGs showed the highest drug release values at condition of 41?°C and pH 5.3. The drug-loaded MNHGs at physiological condition (pH 7.4 and 37?°C) exhibited negligible drug release values. In vitro cytotoxic effects of the DOX-loaded MNHGs were extensively evaluated through the assessing survival rate of HeLa cells using the MTT assay, and there in vitro cellular uptake into the mentioned cell line were examined using fluorescent microscopy and fluorescence-activated cell sorting (FACS) flow cytometry analyses. As the results, the DOX-loaded MNHG1 exhibited higher anticancer drug delivery performance in the terms of cytotoxic effect and in vitro cellular uptake. Thus, the developed MNHG1 can be considered as a promising de novo drug delivery system, in part due to its pH and thermal responsive drug release behavior as well as proper magnetite character toward targeted drug delivery.     

Iridium(III) Complex–Derived Polymeric Micelles with Low Dark Toxicity and Strong NIR Excitation for Phototherapy and Chemotherapy

Iridium(III) complexes are potent candidates for photodynamic therapy. However, their clinical usage is impeded by their poor water solubility, high dark toxicity, and negligible absorption in near‐infrared region (NIR region). Here, it is proposed to solve these challenges by developing an iridium(III) complexe‐based polymeric micelle system. This system is self‐assembled using an iridium(III) complex‐containing amphiphilic block polymer. The upconversion nanoparticles are included in the polymeric micelles to permit NIR excitation. Compared with the nonformulated iridium(III) complexes, under NIR stimulation, this polymeric micelle system exhibits higher ¹O₂ generation efficiency, negligible dark toxicity, excellent tumor‐targeting ability, and synergistic phototherapy–chemotherapy effect both in vitro and in vivo.     

Thermal Stability of Amorphous Hydride Mg_(50)Ni_(50)H_(54) and Mg_(30)Ni_(70)H_(45)

The thermal stability of amorphous ternary hydrides Mg_(50)Ni_(50)H_(54) and Mg_(30)Ni_(70)H_(45) and their corre-sponding amorphous binary alloys Mg_(50)Ni_(50) and Mg_(30)Ni_(70) were studied with X-ray diffraction(XRD) and differential scanning calorimetry(DSC). Samples of the amorphous alloys were preparedby mechanical alloying and the amorphous hydrides were obtained by charging the alloys with gas-eous hydrogen at 3.0 MPa and 423 K. It was found that the amorphous hydrides released most oftheir hydrogen before the crystallization of the essentially hydrogen depleted amorphous alloy. Thecrystallization temperature of amorphous Mg_(50)Ni_(50)H_(54) elevated and that of amorphousMg_(30)Ni_(70)H_(45) did not change in relation to the original binary amorphous alloy. This is very excep-tional for amorphous hydrides. The reason for the effects of hydrogen absorption/desorption on thecrystallization of amorphous alloys was discussed.     

Synergistic Enzyme-Mimetic Catalysis-Based Non-Thermal Sonocavitation and Sonodynamic Therapy for Efficient Hypoxia Relief and Cancer Ablation (Small 42/2023)

Non-invasive cancer treatment strategies that enable local non-thermal ablation, hypoxia relief, and reactive oxygen species (ROS) production to achieve transiently destroying tumor tissue and long-term killing tumor cells would greatly facilitate their clinical applications. However, continuously generating oxygen cavitation nuclei, reducing the transient cavitation sound intensity threshold, relieving hypoxia, and improving its controllability in the ablation area still remains a significant challenge. Here, in this work, an Mn-coordinated polyphthalocyanine sonocavitation agent (Mn-SCA) with large d-π-conjugated network and atomic Mn-N sites is identified for the non-thermal sonocavitation and sonodynamic therapy in the liver cancer ablation. In the tumor microenvironment, the catalytical generation of oxygen assists cavitation formation and generates microjets to ablate liver cancer tissue and relieve hypoxia, this work reports for the first time to utilize the enzymatic properties of Mn-SCA to lower the cavitation threshold in situ. Moreover, under pHIFU irradiation, high reactive oxygen species (ROS) production can be achieved. The two merits in liver cancer ablation are demonstrated by cell destruction and high tumor inhibition efficiency. This work will help deepen the understanding of cavitation ablation and the sonodynamic mechanisms related to the nanostructures and guide the design of sonocavitation agents with high ROS production for solid tumor ablation.     

Plasma surface treatments of poly(l-lactic acid) (PLLA) and poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV)

The surfaces of poly(l-lactic acid) (PLLA) and poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) were modified by oxygen and nitrogen plasma treatments. The physical and chemical surface characteristics were evaluated by contact angle tests, scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). The plasma treatments caused an increase in both contact angle and roughening, altered the surface morphology, inserted polar groups, and, consequently, enhanced the hydrophilicity for both PLLA and PHBV polymers.     

Acousto-optic interaction in alpha-BaB(2)O(4)and Li(2)B(4)O(7) crystals

Experimental studies and analysis of acousto-optic diffraction in alpha-BaB(2)O(4) and Li(2)B(4)O(7) crystals are given. Ultrasonic wave velocity, elastic compliance and stiffness coefficients, and piezo-optic and photoelastic coefficients of alpha-BaB(2)O(4) and Li(2)B(4)O(7) crystals are determined. The acousto-optic figure of merit has been estimated for different possible geometries of acousto-optic interaction. It is shown that the acousto-optic figures of merit for alpha-BaB(2)O(4) crystals reach the value M(2)=(270 +/- 70) x 10(-15) s(3)/kg for the case of interaction with the slowest ultrasonic wave. The directions of propagation and polarization of those acoustic waves are obtained on the basis of construction of acoustic slowness surfaces. The acousto-optic diffraction is experimentally studied for alpha-BaB(2)O(4) and Li(2)B(4)O(7) crystals.