2017 Volume 28 Issue 9

Cell-surface cascaded landing location for nanotheranostics
Ren En , Wang Junqing , Liu Gang
2017, 28(9): 1799-1800  doi: 10.1016/j.cclet.2017.07.015
[Abstract](674) [FullText HTML] [PDF 161KB](0)
Abstract:
Theranostics is an appealing approach in precision medicine and it is still a critical challenge to design smart strategies which can precisely accumulate the functional probes/drugs into targeted disease areas. Cell-surface cascaded landing location is an effective strategy to develop functional drug-loading platforms to explore basic physiological processes at the cellular level and to facilitate the development of nanotheranostics for disease treatment.
Artificial periosteum in bone defect repair-A review
Wang Quan , Xu Jianxiang , Jin Haiming , Zheng Wenhao , Zhang Xiaolei , Huang Yixing , Qian Zhiyong
2017, 28(9): 1801-1807  doi: 10.1016/j.cclet.2017.07.011
[Abstract](682) [FullText HTML] [PDF 434KB](4)
Abstract:
Periosteum is a thin membrane that encases the surfaces of most bones. It is composed of an outer fibrous layer contains longitudinally oriented cells and collagen fibers and an inner cambial layer that consists of multipotent mesenchymal stem cells (MSCs) and osteogenic progenitor cells. Periosteum has a function of regulating cell and collagen arrangement, which is important to the integrity, modelling and remodelling of bone, particularly during bone defect repair. Apart from autograft and allograft, artificial periosteum, or tissue-engineered periosteum mimicking native periosteum in structure or function, made up of small intestinal submucosa, acellular dermis, induced membrane, cell sheets, and polymeric scaffolds, and so on, has been developed to be used in bone defect repair. In this review, we classify the artificial periosteum into three approaches based on the material source, that is, native tissues, scaffoldfree cell sheets and scaffold-cell composites. Mechanisms, methods and efficacy of each approach are provided. Existing obstacles and enabling technologies for future directions are also discussed.
Recent advances of transformable nanoparticles for theranostics
Zhang Kuo , Yang Pei-Pei , Zhang Jing-Ping , Wang Lei , Wang Hao
2017, 28(9): 1808-1816  doi: 10.1016/j.cclet.2017.07.001
[Abstract](655) [FullText HTML] [PDF 985KB](2)
Abstract:
In recent years, various transformable nanoparticles (NPs) were successfully prepared and widely utilized for biomedical applications. The sizes, surface charges or morphologies of transformable NPs would affect their behavior in physiological/pathological conditions including circulation, penetration, accumulation and retention etc. The other way round, the NPs could be precisely modulated in the specific physiological/pathological condition for precision theranostics of diseases. Herein, we summarized recent advances of transformable NPs for disease diagnostics and therapy. In this review, the transformation of NPs was divided into three groups including changes in size, surface charge and morphology, which was induced by internal stimuli, such as pH, enzyme, receptor or external stimuli, such as light, temperature etc. Moreover, we focused on the characterization of structural transformation in vivo, as well as the transformation-induced biological effects for theranostics of disease.
Pediatric ocular nanomedicines:Challenges and opportunities
D. Sheybani Natasha , Yang Hu
2017, 28(9): 1817-1821  doi: 10.1016/j.cclet.2017.07.022
[Abstract](817) [FullText HTML] [PDF 338KB](0)
Abstract:
The eye is a highly complex, yet readily accessible organ within the human body. As such, the eye is an appealing candidate target for a vast array of drug therapies. Despite advances in ocular drug therapy research, the focus on pediatric ocular drug delivery continues to be highly underrepresented due to the limited number of degenerative ocular diseases with childhood onset. In this review, we explore more deeply the reasons underlying the disparity between ocular therapies available for children and for adults by highlighting diseases that most commonly afflict children (with focus on the anterior eye) and existing prognoses, recent developments in ocular drug delivery systems and nanomedicines for children, and barriers to use for pediatric patients
Recent progress on DNA block copolymer
Pan Gaifang , Jin Xin , Mou Quanbing , Zhang Chuan
2017, 28(9): 1822-1828  doi: 10.1016/j.cclet.2017.08.022
[Abstract](638) [FullText HTML] [PDF 626KB](3)
Abstract:
DNA has gained great attention because of its unique structure, excellent molecular recognition property, and biological functions. When married with versatile synthetic polymers, the DNA conjugated polymer hybrids, known as DNA block copolymers (DBCs), have been launched and well developed for the syntheses of new materials and nanostructures with different functions in the past several decades. Compared to conventional synthetic block copolymers, using DNA as a building block provides several advantages over other polymer candidates, such as molecular recognition, programmable self-assembly, biocompatibility, and sequence-encoded information. In this review, recent developments in this area will be summarized and meaningful breakthroughs will be highlighted. We will discuss representative examples of recent progress in the syntheses, structure manipulations, and applications of DBCs.
Development and application of nano-flavor-drug carriers in neurodegenerative diseases
Ji Wei-Hong , Xiao Zuo-Bing , Liu Gui-Ying , Zhang Xin
2017, 28(9): 1829-1834  doi: 10.1016/j.cclet.2017.06.024
[Abstract](630) [FullText HTML] [PDF 182KB](0)
Abstract:
Neurodegenerative disease is one of the serious diseases of the human nervous system. There is no effective way to treat neurodegenerative diseases. Flavors such as curcumin, coumarin, have attracted increasing attention due to having a beneficial therapeutic effect on Alzheimer's disease and Parkinson's disease. But the use of most drugs is limited in clinical treatment because of blood-brain barrier. The use of nano-drug carriers such as liposomes, polymer micelles, polymer nanoparticles and magnetic nanoparticles, which can carry drugs across the blood-brain barrier, has brought hope for the treatment of neurodegenerative diseases.
Self-assembled small molecular weight hydrogels of prodrugs
Zhou Yanfang , Li Xingyi
2017, 28(9): 1835-1840  doi: 10.1016/j.cclet.2017.04.033
[Abstract](579) [FullText HTML] [PDF 380KB](0)
Abstract:
Molecular self-assembly is very ordinary phenomenon in the biological process such as protein folding, DNA encoding and etc. Inspired by this inherent biological process, nanostructure such as nanofibers, nanosphere, and so on formed by the therapeutic agents and its derivatives that can further self-assemble into supramolecular hydrogels have attained considerable attentions in the field of drug delivery due to its favorable features such as high and precise drug payload, carrier-free and excellent biocompatibility. Additionally, the prodrug hydrogelator can be rationally designed to fine-tune over its drug release behavior and degradation in response to various biological stimulus (temperature, pH, ionic strength and etc.). This review summarized and discussed the recent advancement in the self-assembled small molecular weight hydrogels of prodrugs.
H2O2-responsive theranostic nanomedicine
Yu Luodan , Chen Yu , Chen Hangrong
2017, 28(9): 1841-1850  doi: 10.1016/j.cclet.2017.05.023
[Abstract](623) [FullText HTML] [PDF 1312KB](2)
Abstract:
The fast progress of stimuli-responsive theranostic nanomedicine can achieve the specific and highperformance diagnosis and therapy of various diseases. Especially, H2O2-responsive theranostic nanomedicine is recently emerging as a new stimuli-responsive modality showing the great potential for the theranostic of diseases with overexpressed H2O2 because H2O2 is associated with several kinds of human diseases as the most stable and abundant reactive oxygen species. This review summarizes and discusses the very-recent developments of H2O2-responsive theranostic nanoplatforms for versatile biomedical applications, including diagnostic imaging, attenuating tumor hypoxia, enhancing the therapeutic efficiency of photodynamic therapy/radiation therapy/chemotherapy and theranostic of inflammation/diabetic. The facing challenges and future developments of H2O2-responisve theranostics are also briefly discussed to further promote the clinical translation of this new responsive theranostic modality. It is highly believed that H2O2-responsive theranostic nanomedicine will be extensively developed a new specific and efficient theranostic modality to benefit the personalized biomedicine in the near future.
Advances in quantum dot-mediated siRNA delivery
Zhi-Yao He , Jin Zhao-Hui , Zhan Mei , Qin Zhou , Li Zhi , Xu Ting
2017, 28(9): 1851-1856  doi: 10.1016/j.cclet.2017.07.012
[Abstract](631) [FullText HTML] [PDF 328KB](0)
Abstract:
Nano-sized quantum dots (QDs) exhibit uniquely optical properties that are tunable with different sizes and shapes. QDs can emit narrow symmetric bands under a wide excitation range, possess antiphotobleaching stability, and be bio-functionalized on the large surface area. Therefore, QDs are attractive vectors for imaging-guided therapy. Small-interfering RNA (siRNAs)-based therapeutics hold great potential to target a large part of the currently undruggable genes, but overcoming the lipid bilayer to deliver siRNA into cells has remained a major challenge to solve for widespread development of siRNA therapeutics. In this mini-review, we focus on theranostic QD/siRNA assembles for enhancing delivery of siRNA and facilitating evaluation of therapeutic efficacy via imaging of QDs, with special attention to carbonaceous QDs for delivery of siRNA.
The design, mechanism and biomedical application of self-healing hydrogels
Li Qiwen , Liu Chenlu , Wen Junru , Wu Yongzhi , Shan Yue , Liao Jinfeng
2017, 28(9): 1857-1874  doi: 10.1016/j.cclet.2017.05.007
[Abstract](722) [FullText HTML] [PDF 1274KB](5)
Abstract:
Hydrogels are promising materials with outstanding characteristics such as tunable and reversible physical/chemical properties, stimuli-responsiveness, biomimetic, and biocompatibility. However, the structural and functional integrity of the hydrogels can be compromised by external mechanical forces or chemical erosion when used, especially in sophisticated in vivo environment. To address this problem, self-healing hydrogels which possess the intrinsic ability of self-repair have been developed to adapt to destructive factors. In this review, we focused on the current advances made in self-healing hydrogels. First, the testing methods for self-healing hydrogels were summarized. Then, we looked into the designing strategies of self-healing hydrogels and illustrated the self-healing mechanism. What's more, the biomedical application of self-healing hydrogels in vivo was discussed.
PEGylated BODIPY assembling fluorescent nanoparticles for photodynamic therapy
Zhu Yu , Lin Wenhai , Zhang Wei , Feng Yuqin , Wu Zhineng , Chen Li , Xie Zhigang
2017, 28(9): 1875-1877  doi: 10.1016/j.cclet.2017.06.017
[Abstract](654) [FullText HTML] [PDF 310KB](5)
Abstract:
Two amphiphilic macromolecules were synthesized from polyethylene glycol monomethylether (PEG) and borondipyrrolmethene (BODIPY) via one-pot multicomponent Passerini reaction, and they could self-assemble into stable nanoparticles (NPs) in aqueous media. The optical properties, including fluorescence resonance energy transfer (FRET) were studied in detail. The obtained NPs possess good cytocompatibility, and could be used for living cell imaging and effective photodynamic therapy (PDT). These results shed light on one-pot synthesis of PEGylated fluorescent nanoparticles via multicomponent reaction for biomedical application.
pH Readout enhanced ELISA for point-of-care testing of cardiac troponin I
Miao Luyang , Zhang Lianhua , Jiao Lei , Tan Xiaofeng , Wei Qin , Li He
2017, 28(9): 1878-1880  doi: 10.1016/j.cclet.2017.04.018
[Abstract](600) [FullText HTML] [PDF 241KB](1)
Abstract:
Enzyme-linked immunosorbent assay (ELISA) as a conventional method for protein quantification has its characteristic properties, however, it is challenging to implement excellent portability and sensitivity at the same time. In this study, we described a pH ELISA using synthetic melanin nanoparticles (SMNPs) for the co-immobilization of glucose oxidase (GOx) and second antibody (Ab2) as signal labels, portable pH meter as signal readout device for point-of-care testing (POCT) of cardiac troponin I (cTnI). In accordance with the varying amount of cTnI, following sandwich type immunoassay, proportional SMNPs-GOx-Ab2 were immobilized specifically resulting in corresponding decrease of pH values owing to GOx loaded on SMNPs can high-efficiency convert glucose into gluconic acid. This assay is easy-to-use, portable, sensitive and able to realize POCT, affording a linear range from 0.5 pg/mL to 10 ng/mL and low limit of detection (LOD) of 0.15 pg/mL towards cTnI, which was demonstrated the significant promising in the early diagnosis and screening of acute myocardial infarction.
Immune fluorescence test strips based on quantum dots for rapid and quantitative detection of carcino-embryonic antigen
Wu Yudong , Peng Weipan , Zhao Qian , Piao Jiafang , Zhang Bo , Wu Xiaoli , Wang Hanjie , Shi Zhihong , Gong Xiaoqun , Chang Jin
2017, 28(9): 1881-1884  doi: 10.1016/j.cclet.2017.07.026
[Abstract](591) [FullText HTML] [PDF 324KB](1)
Abstract:
At present, many researchers focused on the point-of-care testing (POCT), a method of disease markers detection without large-scale instruments and specialized persons. However, most POCT diagnostic methods were suffered from poor detection sensitivity or inefficiency in quantitative detection. Herein, we developed a newly QD-immune fluorescence test strips (QD-IFTS) based on quantum dots (QDs) as the fluorescence nanocarrier to prepare the immune fluorescence probes in the classical immunochromatography detection system for sensing carcino-embryonic antigen (CEA), a kind of glycoprotein produced by intestinal tissue and a broad spectrum of tumor marker for cancer diagnosis. And we designed a homemade strips fluorescence reader for detection of fluorescence intensity of QDs on the QD-IFTS. Under the optimized reaction conditions, chromatographic time of the newly QD-IFTS was only 25 min, sample volume of the newly QD-IFTS was only 40 μL and the LOD of the newly QD-IFTS was 0.72 ng/mL. In addition, the efficiency and robustness of the newly QD-IFTS were confirmed by successfully application in 300 clinical serum samples, and the results revealed great potential in clinical POCT of other biomarkers.
Fabrication of a polypseudorotaxane nanoparticle with synergistic photodynamic and chemotherapy
Xu Tao-Tao , Li Jun-Hua , Cheng Fu-Rong , Zhang Yi-Xin , Cao Jun , Gao Wen-Xia , He Bin
2017, 28(9): 1885-1888  doi: 10.1016/j.cclet.2017.07.029
[Abstract](585) [FullText HTML] [PDF 423KB](0)
Abstract:
A polypseudorotaxane (PPR) nanoparticle was fabricated by the self-assembly of mPEG-protoporphyrin IX (PpIX) conjugate and α-CDs via the host-guest interaction. The nanoparticle loaded with anticancer drug doxorubicin (DOX) exerted synergistic photodynamic and chemotherapy. The nanoparticle was spherical with the mean size of 89 nm, the low critical micelle concentration (CMC) of DOX-loaded nanoparticle was 9.3 μg/mL and the drug loading content was 9.93%. The in vitro anticancer activity test revealed that the DOX-loaded nanoparticle exhibited promising reactive oxygen species (ROS) cytotoxicity and chemotherapeutic efficacy to cancer cells. The PPR nanoparticle is potentially promising for synergistic photodynamic and chemotherapy for cancers.
C60(OH)n-loaded nanofibrous membranes protect HaCaT cells from ROS-associated damage
Guo Mengyu , Bi Shuying , Liu Jing , Xu Wenshi , Zhou Guoqiang , Liu Ying , Chen Chunying
2017, 28(9): 1889-1892  doi: 10.1016/j.cclet.2017.07.021
[Abstract](609) [FullText HTML] [PDF 386KB](0)
Abstract:
Environmental stress factors could lead to the excess generation of reactive oxygen species (ROS) that induces various forms of skin damage related to oxidative stress. Polyhydroxylated fullerene derivative C60(OH)n, acting as an effective agent for prevention of skin aging, is widely used in the lotion and sunscreens in the field of cosmetics, but rarely used in the masks. In this study, we prepared C60(OH)n loaded nanofibrous membranes to protect human keratinocyte cells from ROS-associated damage and suppress the elevation of intracellular ROS and Ca2+ along with the apoptotic cell death. Two FDAapproved biodegradable polymers, PLGA and PCL, have been used for making the electrospun nanofibers, with C60(OH)n added to the polymers as an antioxidant. The nanofibrous membranes with good biocompatibility might be potentially applied in clinical practice to reduce skin aging.
A potential flower-like coating consisting of calcium-phosphate nanosheets on titanium surface
Ma Quanquan , Liao Jinfeng , Tian Taoran , Zhang Qi , Cai Xiaoxiao
2017, 28(9): 1893-1896  doi: 10.1016/j.cclet.2017.07.028
[Abstract](576) [FullText HTML] [PDF 295KB](0)
Abstract:
Titanium and its alloys have been widely used as implant materials in bio-medicine. Additionally, surface modification has been utilized to improve the chemical and morphological properties of materials. More specifically, biocoating, especially the calcium-phosphate nano-coating, has been widely used in the research field. In this study, a novel calcium-phosphate nanoflower coating was performed on the titanium surface by a simple approach. This study indicated that the novel calcium-phosphate flower-like coating consisting of calcium-phosphate nanosheets had high surface area, low cytotoxicity as well as promising cell affinity. Hence it could be a potential alternative modification method for titanium.
Biocompatible microcapsules with a water core templated from single emulsions
Kong Linlin , Amstad Esther , Hai Mingtan , Ke Xinyou , Chen Dong , Zhao Chun-Xia , Weitz David A.
2017, 28(9): 1897-1900  doi: 10.1016/j.cclet.2017.07.017
[Abstract](565) [FullText HTML] [PDF 329KB](0)
Abstract:
Biocompatible microcapsules with a water core are widely used to encapsulate hydrophilic actives. Here, a facile method to fabricate monodisperse biocompatible microcapsules with a water core in large quantity is reported. Microfluidic technology is utilized to emulsify the inner aqueous phase containing the shell polymer into monodisperse drops in the outer oil phase. As the cosolvent in the inner aqueous phase diffuses into the outer oil phase, the solubility of the shell polymer decreases, which eventually precipitates. Since the shell polymer, shellac, contains both hydrophilic and hydrophobic groups, it tends to wet both the inner aqueous phase and the outer oil phase, thus forming a solid shell at the periphery of the drop. We show that the diffusion rate of hydrophilic molecules encapsulated in the water core decreases as their molecular weight increases and the property of the microcapsules could further be modified by polyelectrolyte multilayer coating. These microcapsules are fabricated using FDA-approved polymer and non-toxic solvents and are of great use in drugs, cosmetics and foods.
11-Mercaptoundecanoic acid functionalized gold nanoclusters as fluorescent probes for the sensitive detection of Cu2+ and Fe3+ ions
Bai Zhiqun , Ren Xiangling , Gong Zhen , Hao Chenxi , Chen Yongmei , Wan Pingyu , Meng Xianwei
2017, 28(9): 1901-1904  doi: 10.1016/j.cclet.2017.05.005
[Abstract](599) [FullText HTML] [PDF 301KB](2)
Abstract:
Metal ions are physiologically essential, but excessive metal ions may cause severe risk to plants and animals. Here, we prepared gold nanoclusters (Au NCs) protected by 11-mercaptoundecanoic acid (11-MUA), which have excellent fluorescence properties for the detection of metal ions. The results showed that the copper ions (Cu2+) and iron ions (Fe3+) in the solution have obvious quenching effect on the fluorescence intensity of Au NCs. The detection range of Fe3+ was 0.8-4.5 mmol/L (R2=0.992) and 4.5-11.0 μmol/L (R2=0.997). And Cu2+ has a lower linear range (0.1-1.0 μmol/L, R2=0.993). When EDTA was added into the reaction system, it was observed that the quenching effect of Cu2+ and Fe3+ on Au NCs showed different phenomenon. Then, the effect of metal ions on the fluorescence of Au NCs was investigated. The selective detection of Cu2+ was achieved by EDTA masking of Fe3+. In addition, we realized the metal ions detection application of Au NCs in the serum
Micelle or polymersome formation by PCL-PEG-PCL copolymers as drug delivery systems
Hu Chunyan , Chen Zhuo , Wu Shengjie , Han Yanfeng , Wang Hai , Sun Hongfan , Kong Deling , Leng Xigang , Wang Chun , Zhang Linhua , Zhu Dunwan
2017, 28(9): 1905-1909  doi: 10.1016/j.cclet.2017.07.020
[Abstract](933) [FullText HTML] [PDF 280KB](5)
Abstract:
Poly(ε-caprolactone)-b-poly(ethylene glycol)-b-poly(ε-caprolactone) (PCL-b-PEG-b-PCL, PCEC) triblock copolymers have been widely investigated in last several decades. Here, by altering the weight ratio of monomers in ring-opening polymerization, a series of PCEC triblock copolymers with varying hydrophobicity were synthesized, which were characterized by FTIR, 1H NMR, GPC and DSC. When PCEC copolymers with different weight ratios of PCL/PEG were dispersed in different aqueous solutions, they could self-assemble and form two distinctive nanoparticular structures:micelles or polymersomes. We then chose paclitaxel (PTX) as the model drug and encapsulate PTX into PCEC polymeric micelles and polymersomes. The physicochemical characterizations of the nanoparticles such as morphology, the size and distribution, zeta potential, drug loading content, and encapsulation efficiency were also performed. Our results showed that polymeric micelles or polymersomes from PCEC both displayed narrow size distributions and could achieve high drug loading efficiencies.In vitro cellular uptake results suggested that Nile Red loaded polymeric micelles or polymersomes displayed more internalization after 24 h incubation than those after 4 h incubation. These findings suggest that polymeric micelles and polymersomes based on PCL-b-PEG-b-PCL copolymers have great potential to effectively delivery hydrophobic drugs.
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