China Takes the Lead in the Structural Determination of Lumbrokinase

After five years of arduous work, CAS scientists re cently succeeded in determining the structure of lumbrokinase (earthworm fibrinolytic enzyme),shedding light on the understanding of this drug at the molecular level and laying a foundation for drug design based on its structure.     

China Takes the Lead in the Structural Determination of Lumbrokinase

After five years of arduous work, CAS scientists recently succeeded in determining the structure of lumbrokinase (earthworm fibrinolytic enzyme), shedding light on the understanding of this drug at the molecular level and laying a foundation for drug design based on its structure.Cardiac and cerebrovascular diseases are among the three most lethal illnesses now rampant in the human population. Eight years ago, Chinese scientists succeeded in extracting lumbrokinase from earth-     

A Fundamental Study and Applied Exploration of Some Novel Photo-functional Materials

This project focuses on fundamental problems in the interdisciplinary research of chemistry and materials,covering main achievements on fundamental study and applied exploration of novel photo-functional materials.     

In pursuit of reconstructing missing human handsOA

<正>Human beings are the most intelligent living beings on Earth.Creating reconstructions of missing human limbs that can be naturally integrated into the human body is a lofty ambition and faces challenges in neuroscience,information science,mechanical and electronic engineering,and many other disciplines.Based on the development history of robotic prosthetic hands over the past 70 years,     

A Fundamental Study and Applied Exploration of Some Novel Photo-functional Materials

This project focuses on fundamental problems in the interdisciplinary research of chemistry and materials, covering main achievements on fundamental study and applied exploration of novel photo-functional materials.Significant progress was made in the design and con- struction of special photo-functional molecules and complexes by implementation of this project. (1) Organic nanomaterials were investigated sys- tematically in this project, extending the particularity of nanomaterials from metal…     

Research casts doubt on independen ancestral origin of cultivated rice

CAS botanists have made novel progress on studies of origin and domestication of the Asian cultivated rice Oryza sativa. Their work was published in the June issue of Genetics.     

Research casts doubt on independent ancestral origin of cultivated rice

CAS botanists have made novel progress on studies of origin and domestication of the Asian cultivated rice Oryza sativa. Their work was published in the June issue of Genetics.     

Self-fueling ferroptosis-inducing microreactors based on p H-responsive Lipiodol Pickering emulsions enable transarterial ferro-embolization therapyOA

Lipiodol chemotherapeutic emulsions remain one of the main choices for the treatment of unresectable hepatocellular carcinoma(HCC) via transarterial chemoembolization(TACE). However, the limited stability of Lipiodol chemotherapeutic emulsions would lead to rapid drug diffusion, which would reduce the therapeutic benefit and cause systemic toxicity of administrated chemotherapeutics. Therefore, the development of enhanced Lipiodol-based formulations is of great significance to enable effective a...     

Nanotechnology for the management of COVID-19 during the pandemic and in the post-pandemic eraOA

Following the global COVID-19 pandemic,nanotechnology has been at the forefront of research efforts and enables the fast development of diagnostic tools,vaccines and antiviral treatment for this novel virus(SARS-CoV-2).In this review,we first summarize nanotechnology with regard to the detection of SARS-C oV-2,including nanoparticle-based techniques such as rapid antigen testing,and nanopore-based se quencing and sensing techniques.Then we investigate nanote chnology as it applies to the develop...     

Climbing robots for manufacturingOA

Robotized intelligent manufacturing is a growing trend in the manufacturing of large and complex components in aviation,aerospace,marine engineering and other industries.With their expansive workspaces and flexible deployment,climbing manufacturing robots can create a revolutionary manufacturing paradigm for large and complex components.This paper defines the climbing manufacturing robot based on the application status of climbing robots and then analyzes four key technical re quirements:adhesio...     

Cell membrane-covered nanoparticles as biomaterials

Surface engineering of synthetic carriers is an essential and important strategy for drug delivery in vivo. However, exogenous properties make synthetic nanosystems invaders that easily trigger the passive immune clearance mechanism, increasing the retention effect caused by the reticuloendothelial systems and bioadhesion, finally leading to low therapeutic efficacy and toxic effects. Recently, a cell membrane cloaking technique has been reported as a novel interfacing approach from the biological/immunological perspective, and has proved useful for improving the performance of synthetic nanocarriers in vivo. After cell membrane cloaking, nanoparticles not only acquire the physiochemical properties of natural cell membranes but also inherit unique biological functions due to the presence of membrane-anchored proteins, antigens, and immunological moieties. The derived biological properties and functions, such as immunosuppressive capability, long circulation time, and targeted recognition integrated in synthetic nanosystems, have enhanced their potential in biomedicine in the future. Here, we review the cell membrane-covered nanosystems, highlight their novelty, introduce relevant biomedical applications, and describe the future prospects for the use of this novel biomimetic system constructed from a combination of cell membranes and synthetic nanomaterials.     

Transportation of AIE-visualized nanoliposomes is dominated by the protein corona

Liposomes, especially cationic liposomes, are the most common and well-investigated nanocarriers for biomedical applications, such as drug and gene delivery. Like other types of nanomaterials, once liposomes are incubated in a biological milieu, their surface can be immediately cloaked by biological components to form a protein corona, which confers a new ‘biological identity’ and modulates downstream interactions with cells. However, it remains unclear how the protein corona affects the transportation mechanism after liposomes interact with cells. Here, we employed home-made aggregation-induced-emission-visualized nanoliposomes TR4@Lipo as a model to investigate transportation with or without the protein corona by optical imaging techniques. The results show that the protein corona can change the cellular transportation mechanism of TR4@Lipo from energy-independent membrane fusion to energy-dependent endocytosis. The protein corona also modulates the intracellular distribution of loaded cargoes. This knowledge furthers our understanding of bio-nano interactions and is important for the efficient use of cationic liposomes.     

Preface to Special Topic: Microfluidics in Drug Delivery

In this special topic of Biomicrofluidics, the importance of microfluidics in the field of drug delivery is highlighted. Different aspects from cell-drug carrier interactions, delivery vehicle assembly to novel drug delivery devices are considered. The contributing reviews and original articles illustrate the synergistic outcomes between these two areas of research with the aim to have a positive impact on biomedical applications.Microfluidics is certainly one of the huge success stories when it comes to anticipated impact and fulfilled promises in academic research environments. Microfluidic approaches are game changers in many disciplines in natural science, including (bio)medical science. In the latter case, the fields of biosensing/diagnostics, tissue engineering, and drug discovery/delivery have benefited from concepts which allow for the fast throughput manipulation of fluids at the submillimeter length scale.A key aim in microfluidic-assisted drug discovery is the development of strategies which will facilitate the identification of potential “hits”—new drugs with the anticipated therapeutic benefit. In this context, “organ(disease)-on-chips” are considered as highly sophisticated in vitro models with lower cost and less ethical issues compared to extensive testing in animals. This technology is still very young with countless research challenges to be addressed and eventually overcome, but the few current reports are promising, and include “gut-on-chip,” “cancer-on-chip,” or “blood vessel-on-chip.” Additionally, intravenously injected drug delivery vehicles are exposed to the blood stream and the induced mechanical forces which are likely to affect their interaction with cells and tissue. Therefore, understanding the diffusion phenomena of biomolecules in microfluidic devices as reviewed by Yesil-Celiktas and coworkers in the current special content is crucial.¹ What is more, the contribution by Hosta-Rigau and colleagues provides a comprehensive overview over the interaction of drug carriers and cells in microfluidic-based systems which deliver a simple, but yet more realistic model of the dynamic in vivo situation.² Further, to illustrate the relevance of shear stress when assessing the potential of nanocarriers for drug delivery applications, we assembled novel block copolymers consisting of poly(cholesteryl acrylate) as the hydrophobic core and poly(N-isopropylacrylamide) as the hydrophilic extensions together with lipids into vesicles using the evaporation-rehydration method.³ Following on, we biologically evaluated the assemblies with applied shear stress using macrophages. In a related report by the Chakraborty group, a biocompatible acoustic microfluidic system was outlined including the effect of microbubbles with the applied acoustic field on biological cells.⁴From a different perspective, droplet microfluidics has become a popular method to assemble a huge diversity of particles of different size, shape, and morphology equipped with options for active or passive drug release. Microfluidics provides unique opportunities and flexibility to fabricate decent amounts of mono-disperse drug carriers using monomers, polymers, lipids, or inorganic precursor materials as building blocks. The assembly of size-tunable polymer/lipid particles by Sun et al.,⁵ and the fabrication of poly (lactic-co-glycolic acid) nanoparticles incorporated within poly (ethylene glycol) (PEG) microgels by the Chen group,⁶ provide interesting examples in this context. Further, artefacts associated with this technique have to be addressed and understood to avoid inaccurate and misleading data as reported by Litten et al.⁷ Microfluidic techniques can also be employed for cell encapsulation. Fan et al. demonstrated the trapping of human colon cancer cells in hydrogel particles with preserved viability and response to inflammatory stimuli.⁸Novel drug delivery devices which consider microfluidic concepts and set-ups are an interesting addition to traditional approaches. Implantable drug delivery systems provide an alternative to ensure constant drug level in blood without relying on the compliance of the patient while circumventing challenges involved in oral drug delivery coming from drug instability or limited absorbance among others. Yi and coworkers propose a reservoir approach in combination with a heat responsive valve towards the long term delivery of solid drugs.⁹ What is more, nebulizers, as alternative to inhalers for pulmonary drug delivery, suffer from miniaturization and drug degradation issues. Cortez-Jugo et al. report on a novel portable acoustomicrofluidic device, which successfully nebulized monoclonal antibodies into a fine aerosol mist including the first positive biological evaluation.¹⁰Further, combining microfluidics with sensing concepts as illustrated by Knoll and coworker¹¹ is of importance, since the design of drug delivery vehicles strongly relies on the fundamental understanding of the interaction between biomolecules, cells, and tissue.Taken together, these articles give an overview over the use of microfluidics in the area of drug delivery, which goes beyond the assembly of drug carries, but also provides a platform for their biological evaluation or the design of entirely new drug delivery devices. I hope that this collection of articles will stimulate new ideas and future collaborations between engineers/chemists/physicist and biologists towards the common goal to provide solutions for biomedical challenges. Finally, I would like to thank Professor Leslie Yeo for the invitation to be the guest editor for this special topic, and Christine Urso and other editorial and production staffs of Biomicrofluidics for making it a reality.     

Preparation,Characterization and Cytotoxic Effects of Pegylated Nanoliposomal Containing Carboplatin on Ovarian Cancer Cell Lines

Carboplatin is a chemotherapeutic agent used against various malignancies such as ovarian carcinoma. The aim of this study is to improve the therapeutic efficacy of carboplatin using pegylated liposomal nanocarriers. Nanoparticles were synthesized using thin film hydration technique and characterized for shape morphology, particle size, zeta potential and drug-release properties. In the next step, A2780S and A2780CP ovarian cancer cell lines were used to determine the efficacy of nanodrug by MTT assay. The particle size and zeta potential of nanodrug were measured 244.3 ± 19.6 nm and ?22.9 ± 1.7 mV, respectively. High encapsulation capacity (78.6 ± 3.7 %) confirmed the efficiency of technique. The cytotoxicity results also showed that nanodrug compared to free drug improve the efficacy of carboplatin against both A2780S (P < 0.01) and A2780CP (P < 0.05) cell lines. In conclusion, the findings of our study suggested pegylated liposomal nanocarriers are proper for carboplatin delivery to ovarian cancer cell lines A2780S and A2780CP.     

Development of vertical SU-8 microtubes integrated with dissolvable tips for transdermal drug delivery

Polymer-based microneedles have drawn much attention in the transdermal drug delivery resulting from their flexibility and biocompatibility. Traditional fabrication approach deploys various kinds of molds to create sharp tips at the end of needles for the penetration purpose. This approach is usually time-consuming and expensive. In this study, we developed an innovative fabrication process to make biocompatible SU-8 microtubes integrated with biodissolvable maltose tips as novel microneedles for the transdermal drug delivery applications. These microneedles can easily penetrate the skin''s outer barrier represented by the stratum corneum (SC) layer. The drug delivery device of mironeedles array with 1000 μm spacing between adjacent microneedles is proven to be able to penetrate porcine cadaver skins successfully. The maximum loading force on the individual microneedle can be as large as 7.36 ± 0.48N. After 9 min of the penetration, all the maltose tips are dissolved in the tissue. Drugs can be further delivered via these open biocompatible SU-8 microtubes in a continuous flow manner. The permeation patterns caused by the solution containing Rhodamine 110 at different depths from skin surface were characterized via a confocal microscope. It shows successful implementation of the microneedle function for fabricated devices.     

A remotely operated drug delivery system with an electrolytic pump and a thermo-responsive valve

Implantable drug delivery devices are becoming attractive due to their abilities of targeted and controlled dose release. Currently, two important issues are functional lifetime and non-controlled drug diffusion. In this work, we present a drug delivery device combining an electrolytic pump and a thermo-responsive valve, which are both remotely controlled by an electromagnetic field (40.5 mT and 450 kHz). Our proposed device exhibits a novel operation mechanism for long-term therapeutic treatments using a solid drug in reservoir approach. Our device also prevents undesired drug liquid diffusions. When the electromagnetic field is on, the electrolysis-induced bubble drives the drug liquid towards the Poly (N-Isopropylacrylamide) (PNIPAM) valve that consists of PNIPAM and iron micro-particles. The heat generated by the iron micro-particles causes the PNIPAM to shrink, resulting in an open valve. When the electromagnetic field is turned off, the PNIPAM starts to swell. In the meantime, the bubbles are catalytically recombined into water, reducing the pressure inside the pumping chamber, which leads to the refilling of the fresh liquid from outside the device. A catalytic reformer is included, allowing more liquid refilling during the limited valve''s closing time. The amount of body liquid that refills the drug reservoir can further dissolve the solid drug, forming a reproducible drug solution for the next dose. By repeatedly turning on and off the electromagnetic field, the drug dose can be cyclically released, and the exit port of the device is effectively controlled.     

Multimodal channel cancer chemotherapy by 2D functional gadolinium metal–organic framework

2D nanomaterials generally exhibit enhanced physiochemical and biological functions in biomedical applications due to their high surface-to-volume ratio and surface charge. Conventional cancer chemotherapy based on nanomaterials has been hindered by their low drug loading and poor penetration in tumor tissue. To overcome these difficulties, novel materials systems are urgently needed. Hereby, the lanthanide-based porphyrin metal–organic framework (MOF) nanosheets (NSs) with promising cancer imaging/chemotherapy capacities are fabricated, which display superior performance in the drug loading and tumor tissue penetration. The biodegradable PPF-Gd NSs deliver an ultrahigh drug loading (>1500%) and demonstrate the stable and highly sensitive stimuli-responsive degradation/release for multimodal tumor imaging and cancer chemotherapy. Meanwhile, PPF-Gd NSs also exhibit excellent fluorescence and magnetic resonance imaging capability in vitro and in vivo. Compared to the traditional doxorubicin (DOX) chemotherapy, the in vivo results confirm the evident suppression of the tumor growth by the PPF-Gd/DOX drug delivery system with negligible side effects. This work further supports the potential of lanthanide-based MOF nanomaterials as biodegradable systems to promote the cancer theranostics technology development in the future.     

Drug Delivery of Hydroxyurea to Breast Cancer Using Liposomes

It is clear that cancer is one of the most mortal diseases in the world and the most prevalent among women is breast cancer. As hydroxyurea (HU)—a drug which is used in chemotherapy—has many adverse effects in long-term despite of its therapeutic properties, we made use of nano drug delivery technology in order to reduce adverse effects and increase therapeutic index. Thus, liposomation is a novel way in drug delivery systems. In this study a mixture of phosphatidylcholine and cholesterol was mixed and HU was added to the resultant mixture. The mean diameter of the nanoliposomal HU measured with the Zeta Sizer device (equal to 402.5 nm) and its encapsulation efficiency was 70.8 %. Besides, using dialysis, the pattern of drug release from nanoliposomes has been studied and the results showed that the drug release of nanoliposomal drug within 28 h was equal to 25.85 %. This study showed that the cytotoxicity effect of nanoliposomal drug is more than that of the standard drug.     

The 2008 Benjamin Franklin Medal in Chemistry is presented to Albert Eschenmoser, Dr. sc.nat

The Franklin Institute, Philadelphia, Pennsylvania, awards the 2008 Benjamin Franklin Medal in Chemistry to Professor Albert Eschenmoser for his seminal efforts in the chemical etiology of nucleic acid structure, which through systematic exploration employing chemical synthesis of potentially natural structural alternatives to DNA, demonstrated that Watson-Crick base pairing is not unique to the ribofuranosyl system, and that DNA’s structure represents an optimization of several factors rather than a maximization of base-pairing strength.In his early scientific career, Professor Albert Eschenmoser established himself as one of the premier synthetic organic chemists in the world, with the monumental achievement of two total syntheses of Vitamin B₁₂, the first in collaboration with Professor Robert B. Woodward of Harvard University.However, since the 1980s, Professor Eschenmoser has concentrated his research interest in establishing the area of chemical etiology of nucleic acid structures to understand better the structural and functional uniqueness of the molecular basis of nature’s genetic information carrier—DNA and RNA. This systematic investigation of potential natural nucleic acid alternatives has demonstrated experimentally that Watson-Crick base pairing is not a unique property of DNA and RNA. Moreover, his research on homo-DNA revealed that the helicality of the famous double-stranded DNA is a direct outcome of the 5-membered ring nature of the deoxyribofuranose structure unit, while the study on p-RNA demonstrated that nature did not choose her genetic system by the standard of maximal base pairing strength, but instead optimization. Of equal significance, his recent design and synthesis of TNA (α-threofuranosyl nucleic acid), found to possess extraordinary base-paring properties, led to the hypothesis suggesting TNA as a possible precursor to the “RNA World”. Finally, his research on the correlation between the differences in the pKa of nucleic bases and their base-pairing strength led to a novel principal for the selection of nucleic base alternatives with proper bonding strength.     

Osmotically driven drug delivery through remote-controlled magnetic nanocomposite membranes

Implantable drug delivery systems can provide long-term reliability, controllability, and biocompatibility, and have been used in many applications, including cancer pain and non-malignant pain treatment. However, many of the available systems are limited to zero-order, inconsistent, or single burst event drug release. To address these limitations, we demonstrate prototypes of a remotely operated drug delivery device that offers controllability of drug release profiles, using osmotic pumping as a pressure source and magnetically triggered membranes as switchable on-demand valves. The membranes are made of either ethyl cellulose, or the proposed stronger cellulose acetate polymer, mixed with thermosensitive poly(N-isopropylacrylamide) hydrogel and superparamagnetic iron oxide particles. The prototype devices'' drug diffusion rates are on the order of 0.5–2 μg/h for higher release rate designs, and 12–40 ng/h for lower release rates, with maximum release ratios of 4.2 and 3.2, respectively. The devices exhibit increased drug delivery rates with higher osmotic pumping rates or with magnetically increased membrane porosity. Furthermore, by vapor deposition of a cyanoacrylate layer, a drastic reduction of the drug delivery rate from micrograms down to tens of nanograms per hour is achieved. By utilizing magnetic membranes as the valve-control mechanism, triggered remotely by means of induction heating, the demonstrated drug delivery devices benefit from having the power source external to the system, eliminating the need for a battery. These designs multiply the potential approaches towards increasing the on-demand controllability and customizability of drug delivery profiles in the expanding field of implantable drug delivery systems, with the future possibility of remotely controlling the pressure source.