Pneumonia is the major cause of death in children under five, particularly in developing countries. Antibiotics such as amoxicillin greatly help in mitigating this problem. However, there is a lack of an infant/toddler-friendly formulation for countries with limited clean water orr electricity. Here, we report the development of a shear-thinning hydrogel system for the oral delivery of amoxicillin to infant/toddler patients, without the need of clean water and refrigeration. The hydrogel formulation consists of metolose (hydroxypropyl methylcellulose) and amoxicillin. It preserves the structural integrity of antibiotics and their antibacterial activity over 12 weeks at room temperature. Pharmacokinetic profiling of mice reveals that the hydrogel formulation increases the bioavailability of drugs by ∼18% compared to that with aqueous amoxicillin formulation. More importantly, oral gavage of this formulation in a mouse model of secondary pneumococcal pneumonia significantly ameliorates inflammatory infiltration and tissue damage in lungs, with a 10-fold reduction in bacterial counts compared to those in untreated ones. Given the remarkable antibacterial efficacy as well as the use of FDA-regulated ingredients (metolose and amoxicillin), the hydrogel formulation holds great promise for rapid clinical translation.Keywords: amoxicillin; metolose; pediatric formulation; pneumonia; shear-thinning hydrogel;

Abnormal (keloid and hypertrophic) scars are a significant affliction with no satisfactory single modality therapy to-date. Available options are often ineffective, painful, potentially hazardous, and require healthcare personnel involvement. Herein a self-administered microneedle device based on drug-free physical contact for inhibiting abnormal scars is reported. Its therapeutic activity through microneedle contact eliminates hazards associated with toxic anti-scarring drugs while self-treatment enables administration flexibility.The microneedle patch was fabricated with FDA-approved liquid crystalline polymer under good manufacturing practice. It was first tested to ascertain its ability to inhibit (keloid) fibroblast proliferation. Later the microneedle patch was examined on the rabbit ear hypertrophic scar model to explore its potential in inhibiting the generation of abnormal scars post-injury. Finally, the microneedle patch was applied to the caudal region of a hypertrophic scar located on a female patient’s dorsum to verify clinical efficacy.On untreated control cultures, barely any non-viable fibroblasts could be seen. After 12-h treatment with the microneedle patch, the non-viable proportion increased to 83.8 ± 11.96%. In rabbit ear hypertrophic scar model, 100% of the control wounds without the presence of patches on rabbit ears generated regions of raised dermis originating from the wound site (3/3), whereas microneedle treatment prevented dermis tissue thickening in 83.33% of the wounds (15/18). In the clinical test, the microneedle patch was well tolerated by the patient. Compared to the untreated region, microneedle treatment decreased the number of infiltrated inflammatory cells, with less disrupted dermis tissue architecture and more flattened appearance.A self-administered, drug-free microneedle patch appears highly promising in reducing abnormal scarring as observed from in vitro, in vivo and clinical experiments. Larger cohort clinical studies need to be performed to validate its efficacy on abnormal scars.

Microneedles are an efficient and minimally invasive approach to transdermal drug delivery and extraction of skin interstitial fluid. Compared to solid microneedles made of silicon, metals and ceramics, polymeric microneedles have attracted extensive attention due to their excellent biocompatibility, biodegradability and nontoxicity. They are easy to fabricate in large scale and can load drugs in high amounts. More importantly, polymers with different degradation profiles, swelling properties, and responses to biological/physical stimuli can be employed to fabricate polymeric microneedles with different mechanical properties and performance. This review provides a guideline for the selection of polymers and the corresponding fabrication methods for polymeric microneedles while summarizing their recent application in drug delivery and fluid extraction. It should be noted that although polymeric microneedles can achieve efficient transdermal delivery of drugs, their wide applications were limited by their unsatisfactory transdermal therapeutic efficiency. Delivery of nanomedicines that incorporate drugs into functional nanoparticles/capsules can address this problem and thus may be an interesting direction in the future.

Embryonic stem cells (ESCs)-derived embryoid body (EB) is a powerful model for the study of early embryonic development and the discovery of therapeutics for tissue regeneration. This article reports a smart nanosensor platform for labeling and tracking the survival and distribution of ESCs during the EB development in a real-time and non-invasive way. Compared with the cell tracker (i.e. DiO) and the green fluorescent protein (GFP), nanosensors provide the homogenous and highly-efficient ESC labeling. Following the internalization, intracellular nanosensors gradually release the non-fluorescent molecules that become fluorescent only in viable cells. This allows a continuous monitoring of ESC survival and distribution during the process of EB formation. Finally, we confirm that nanosensor labeling does not cause the significant influences to biological properties of the ESCs and EBs.Statement of SignificanceThe distribution pattern of viable embryonic stem cells (ESCs) within embryoid body (EB) is closely related with the maturation of EBs. Noninvasive and real-time monitoring of viable ESC distribution in EBs would allow researchers to optimize the culturing condition in time during the EB development and to select the suitable EBs for subsequent applications.Download high-res image (162KB)Download full-size image

This work investigated the antimicrobial activity of Ag octahedral nanoparticle containing polycaprolactone scaffolds (Ag–PCL) that is fabricated via cryomilling. The fabricated composite scaffolds exhibited localized antibacterial activity with no adverse effects on viability and osteogenic differentiation of human fetal mesenchymal stem cells (hfMSCs). Compared to plain PCL scaffolds, the Ag–PCL scaffolds significantly reduce bacteria survival to 32.2% over a 4 hour incubation.

Skin interstitial fluid (ISF) is an emerging source of biomarkers for disease diagnosis and prognosis. Microneedle (MN) patch has been identified as an ideal platform to extract ISF from the skin due to its pain-free and easy-to-administrated properties. However, long sampling time is still a serious problem which impedes timely metabolic analysis. In this study, a swellable MN patch that can rapidly extract ISF is developed. The MN patch is made of methacrylated hyaluronic acid (MeHA) and further crosslinked through UV irradiation. Owing to the supreme water affinity of MeHA, this MN patch can extract sufficient ISF in a short time without the assistance of extra devices, which remarkably facilitates timely metabolic analysis. Due to covalent crosslinked network, the MN patch maintains the structure integrity in the swelling hydrated state without leaving residues in skin after usage. More importantly, the extracted ISF metabolites can be efficiently recovered from MN patch by centrifugation for the subsequent offline analysis of metabolites such as glucose and cholesterol. Given the recent trend of easy-to-use point-of-care devices for personal healthcare monitoring, this study opens a new avenue for the development of MN-based microdevices for sampling ISF and minimally invasive metabolic detection.

Tissue adhesives have emerged as alternatives to suturing and stapling in the treatment of reconnection of injured tissues. They can be accurately applied to the regions of body that are not easy to access in a minimally invasive way without a high level of training. Recently, it was demonstrated that nanoparticles can directly glue hydrogels or tissues without the need for in situ polymerization or crosslinking. For example, silica nanoparticles can serve as connectors between tissues and exhibit adhesion even in the presence of blood. This work reports the adhesive effect of two antimicrobial nanoparticles, i.e. titanium dioxide and zinc oxide nanoparticles, between hydrogels, hydrogel/polymer, and liver tissues. These two nanoparticles exhibit comparable or even better adhesive effects in comparison to silica nanoparticles. In a skin wound mouse model, zinc oxide nanoparticles achieve successful wound closure and aesthetic wound healing, suggesting their capability as an effective antimicrobial tissue adhesive.

Magnetic microbubbles (MMBs) are microbubbles (MBs) coated with magnetic nanoparticles (NPs). MMBs not only maintain the acoustic properties of MBs, but also serve as an important contrast agent for magnetic resonance imaging. Such dual-modality functionality makes MMBs particularly useful for a wide range of biomedical applications, such as localized drug/gene delivery. This article reports the ability of MMBs to release their particle cargo on demand under stable oscillation. When stimulated by ultrasound at resonant frequencies, MMBs of 450 nm to 200 μm oscillate in volume and surface modes. Above an oscillation threshold, NPs are released from the MMB shell and can travel hundreds of micrometers from the surface of the bubble. The migration of NPs from MMBs can be described with a force balance model. With this technology, we deliver doxorubicin-containing poly(lactic-co-glycolic acid) particles across a physiological barrier both in vitro and in vivo, with a 18-fold and 5-fold increase in NP delivery to the heart tissue of zebrafish and tumor tissue of mouse, respectively. The penetration of released NPs in tissues is also improved. The ability to remotely control the release of NPs from MMBs suggests opportunities for targeted drug delivery through/into tissues that are not easily diffused through or penetrated.

Bionanocomposites need to have a homogeneous distribution of nanomaterials in the polymeric matrix to achieve consistent mechanical and biological functions. However, a significant challenge lies in achieving the homogeneous distribution of nanomaterials, particularly through a solvent-free approach. This report introduces a technology to address this need. Specifically, cryomilling, a solvent-free, low-temperature processing method, was applied to generate a bionanocomposite film with well-dispersed nanoparticles. As a proof-of-concept, polycaprolactone (PCL) and doxorubicin-containing silica nanoparticles (Si-Dox) were processed through cryomilling and subsequently heat pressed to form the PCL/Si-Dox (cPCL/Si-Dox) film. Homogeneous distribution of Si-Dox was observed under both confocal imaging and atomic force microscopy imaging. The mechanical properties of cPCL/Si-Dox were comparable to those of the pure PCL film. Subsequent in vitro release profiles suggested that sustained release of Dox from the cPCL/Si-Dox film was achievable over 50 days. When human cervical cancer cells were seeded directly on these films, uptake of Dox was observed as early as day 1 and significant inhibition of cell growth was recorded on day 5.

Noninvasive and longitudinal monitoring of gene expression in living cells is essential for understanding and monitoring cellular activities. Herein, a smart magnetic nanosensor is constructed for the real-time, noninvasive, and longitudinal monitoring of cellular mRNA expression through the layer-by-layer deposition of molecular beacons (MBs) and polyethylenimine on the iron oxide nanoparticles. The loading of MBs, responsible for the signal intensity and the tracking time, was easily tuned with the number of layers incorporated. The idea was first demonstrated with the magnetic nanosensors for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, which was efficiently internalized into the cells under the influence of magnetic field. This nanosensor allowed the continuous monitoring of the cellular GAPDH mRNA expression for 1 month. Then this platform was further utilized to incorporate two kinds of MBs for alkaline phosphatase (ALP) and GAPDH mRNAs, respectively. The multifunctional nanosensors permitted the simultaneous monitoring of the reference gene (GAPDH mRNA) and the early osteogenic differentiation marker (ALP mRNA) expression. When the fluorescence signal ratio between ALP mRNA MBs and GAPDH mRNA MBs was taken, the dynamic osteogenic differentiation process of MSCs was accurately monitored.Keywords: layer-by-layer deposition; magnetic nanoparticle; molecular beacon; mRNA detection; nanosensor; osteogenic differentiation

Cellular labeling with inorganic nanoparticles such as magnetic iron oxide nanoparticles, quantum dots, and fluorescent silica nanoparticles is an important method for the noninvasive visualization of cells using various imaging modalities. Currently, this is mainly achieved through the incubation of cultured cells with the nanoparticles that eventually reach the intracellular compartment through specific or nonspecific internalization. This classic method is advantageous in terms of simplicity and convenience, but it suffers from issues such as difficulties in fully removing free nanoparticles (suspended in solution) and the lack of selectivity on cell types. This article reports an innovative strategy for the specific labeling of adherent cells without the concern of freely suspended nanoparticles. This method relies on a nanocomposite film that is prepared by homogeneously dispersing nanoparticles within a biodegradable polymeric film. When adherent cells are seeded on the film, they adhere, spread, and filtrate into the film through the micropores formed during the film fabrication. The pre-embedded nanoparticles are thus internalized by the cells during this infiltration process. As an example, fluorescent silica nanoparticles were homogeneously distributed within a polycaprolactone film by utilizing cryomilling and heat pressing. Upon incubation within physiological buffer, no silica nanoparticles were released from the nanocomposite film even after 20 d of incubation. However, when adherent cells (e.g., human mesenchymal stem cells) were grown on the film, they became fluorescent after 3 d, which suggests internalization of silica nanoparticles by cells. In comparison, the suspension cells (e.g., monocytes) in the medium remained nonfluorescent no matter whether there was the presence of adherent cells or not. This strategy eventually allowed the selective and concomitant labeling of mesenchymal stem cells during their harvest from bone marrow aspiration.Keywords: adherent cells; bone marrow aspiration; mesenchymal stem cells; nanocomposite polymeric film; nanoparticles; selective cell labeling

This report describes the design and synthesis of gold nanostars (AuNSs) containing liposomes by the in situ reduction of gold precursor, HAuCl4 (pre-encapsulated within the liposomes) through HEPES diffusion and reduction. Compared with the conventional process that encapsulates the pre-synthesized gold nanoparticles into liposomes during the thin-film hydration step, this facile and convenient method allows the formation and simultaneous encapsulation of AuNSs within liposomes. The absorption spectra of AuNSs can be tuned between visible and near infra-red (NIR) regions by controlling the size and morphology of AuNSs through varying the concentrations of HAuCl4 and HEPES. As a proof of concept, we demonstrate the synthesis of AuNSs with a maximum absorbance at 803 nmwithin the temperature-sensitive liposomes. These liposomes can produce stronger photoacoustic signals (1.5 fold) in the NIR region than blood. Furthermore, when there are drugs (i.e., doxorubicin) within these liposomes, the irradiation with the NIR pulse laser will disrupt the liposomes and trigger the 100% release of these pre-encapsulated drugs within 10 seconds. In comparison, there is neglectable contrast enhancement or minor release (10%) of drugs for the pure liposomes under the same conditions. Finally, cell experiment shows the potential therapeutic application of this system.本文通过在脂质体内还原金的前体HAuCl4原位合成了金纳米星. 这种设计跟常用的在脂质体内装载金纳米球的方法相比, 优点是方 便快捷的同时实现了金纳米材料的形成和装载. 通过改变实验条件, 合成的金纳米星具有可控的尺寸, 以及在可见区到近红外区之间的可 控吸收光谱. 作为一个例子, 我们在脂质体内合成了最大吸收在803nm的金纳米星. 这种材料具有温度敏感性, 在近红外区可以产生比血液 好1.5倍的光声造影信号. 当我们把抗癌药物阿霉素装载到这种脂质体内时, 近红外区的激光照射可以在10秒内触发药物100%的释放. 相对应的, 不含纳米星的脂质体在同等条件下只能释放10%的药物, 也不具备光声造影的信号增强. 最后, 我们在癌细胞内测试了该脂质体的疗效, 初步验证了该体系的应用前景.

•Quantum Dots (QDs) are good candidates to label Pseudomonas aeruginosa, a Gram-negative pathogen, for imaging purposes.•Heat shock method was found to be an efficient and harmless labeling method for labeling P. aeruginosa with QDs.•The heat shock process does not show any negative effect over the cells activity even at sub-toxic concentrations.Biocompatible nanoparticles are good candidates to label bacteria for imaging and diagnosis purposes. A high labeling efficiency reduces the concentration of nanoparticles required for labeling and allows the labeled bacteria to be tracked for longer periods. This report explores the optimal labeling strategy for Pseudomonas aeruginosa, a common gram-negative opportunistic pathogen, with quantum dots. Three strategies including direct incubation, calcium chloride treatment, and heat shock are compared and the labeling efficiency is assessed through fluorescence microscopy and flow cytometry analysis. Of the three, heat shock is finally selected due to its comparable labeling efficiency and simplicity. Through the assay of the respiration rate of bacteria together with morphology analysis, the heat shock process does not show any negative effect over the cells activity even at sub-toxic concentrations.

Regenerative medicine, which replaces or regenerates human cells, tissues or organs, to restore or establish normal function, is one of the fastest-evolving interdisciplinary fields in healthcare. Over 200 regenerative medicine products, including cell-based therapies, tissue-engineered biomaterials, scaffolds and implantable devices, have been used in clinical development for diseases such as diabetes and inflammatory and immune diseases. To facilitate the translation of regenerative medicine from research to clinic, nanotechnology, especially magnetic nanoparticles have attracted extensive attention due to their unique optical, electrical, and magnetic properties and specific dimensions. In this review paper, we intend to summarize current advances, challenges, and future opportunities of magnetic nanoparticles for regenerative medicine.

Assessment of intracellular mRNA expression is invaluable for understanding cellular signaling activities, identifying disease stages, and monitoring the gene expression pattern of therapeutic cells during their culture, expansion and/or differentiation process. Previous methods suffer from the need to disrupt the biological samples to perform polymerase chain reaction analysis which can be laborious, fragmented and destructive. Herein, we develop a mRNA nanosensor based on the sustained release of mRNA-specific molecular beacons (probes that fluoresce upon hybridization) from the biodegradable poly(D,L-lactide-co-glycolide) nanoparticles. Post cellular internalization, the particles gradually degrade and release the encapsulated probes which are initially weakly fluorescent. When the released probes meet and hybridize with target mRNA, they restore pre-quenched fluorescence. By virtue of quantifying the fluorescence intensity, we can estimate the cellular mRNA expression. As a case study, β-actin mRNA expression in mesenchymal stem cells cultured on a 3D matrix was monitored and compared with those cultured on a 2D plate for one week. Critically, the observed expression profile shows a great correlation with the established quantitative polymerase chain reaction analysis.

Heterogeneous Au–Fe3O4 dumbbell nanoparticles (NPs) are composed of Au NPs and Fe3O4 NPs that bring in optical and magnetic properties respectively. This article reports the engineering of Au–Fe3O4 NPs as gene carriers for magnetic gene transfection as well as contrast agents for micro-optical coherence tomography (μOCT). As a proof-of-concept, Au–Fe3O4 NPs are used to deliver the green fluorescent protein to HEK 293T cells and their entrance into the cells is monitored through μOCT.

Stem cell tracking can reveal the underlying biological processes of stem-cell-based therapies such as the migration and biodistribution of human mesenchymal stem cells (hMSCs) in cancer therapy. Nanoparticle-based contrast agents offer unprecedented opportunities for achieving this goal due to their unique and tunable imaging capabilities. However, most nanoparticles are still in the process of development due to challenges such as retention time and safety issues, and are inaccessible to most researchers. In this article, we investigate the potential application of core–shell fluorescent silica nanoparticles (i.e. C dots), which are commercially available and approved by the FDA for clinical trials. Specifically we demonstrate that 500 nm C dots have prolonged cellular retention (up to one month), minimal contrast agent transfer (at least three weeks) between cells in a co-culture Boyden chamber system, and minimal influence on the hMSC properties including viability, proliferation, differentiation, and tropism to tumor cells.

Engineering cells with active-ingredient-loaded micro/nanoparticles is becoming increasingly popular for imaging and therapeutic applications. A critical yet inadequately addressed issue during its implementation concerns the significant number of particles that remain unbound following the engineering process, which inadvertently generate signals and impart transformative effects onto neighboring nontarget cells. Here we demonstrate that those unbound micro/nanoparticles remaining in solution can be efficiently separated from the particle-labeled cells by implementing a fast, continuous, and high-throughput Dean flow fractionation (DFF) microfluidic device. As proof-of-concept, we applied the DFF microfluidic device for buffer exchange to sort labeled suspension cells (THP-1) from unbound fluorescent dye and dye-loaded micro/nanoparticles. Compared to conventional centrifugation, the depletion efficiency of free dyes or particles was improved 20-fold and the mislabeling of nontarget bystander cells by free particles was minimized. The microfluidic device was adapted to further accommodate heterogeneous-sized mesenchymal stem cells (MSCs). Complete removal of unbound nanoparticles using DFF led to the usage of engineered MSCs without exerting off-target transformative effects on the functional properties of neighboring endothelial cells. Apart from its effectiveness in removing free particles, this strategy is also efficient and scalable. It could continuously process cell solutions with concentrations up to 107 cells·mL–1 (cell densities commonly encountered during cell therapy) without observable loss of performance. Successful implementation of this technology is expected to pave the way for interference-free clinical application of micro/nanoparticle engineered cells.Keywords: cell engineering; cell separation; Dean flow fractionation; microfluidics; nanoparticle

Nucleic acid therapeutics (NATs) are valuable tools in the modulation of gene expression in a highly specific manner. So far, NATs have been actively pursued in both pre-clinical and clinical studies to treat diseases such as cancer, infectious and inflammatory diseases. However, the clinical application of NATs remains a considerable challenge owing to their limited cellular uptake, low biological stability, off-target effect, and unfavorable pharmacokinetics. One concept to address these issues is to deliver NATs within stimuli-responsive liposomes, which release their contents of NATs upon encountering environmental changes such as temperature, pH, and ion strength. In this case, before reaching the targeted tissue/organ, NATs are protected from degradation by enzymes and immune system. Once at the area of interest, localized and targeted delivery can be achieved with minimal influence to other parts of the body. Here, we discuss the latest developments and existing challenges in this field.From the Clinical EditorNucleic acid therapeutics have been shown to enhance or eliminate specific gene expression in experimental research. Unfortunately, clinical applications have so far not been realized due to problems of easy degradation and possible toxicity. The use of nanosized carriers such as liposomes to deliver nucleic acids is one solution to overcome these problems. In this review article the authors describe and discuss the potentials of various trigger-responsive "smart" liposomes, with a view to help other researchers to design better liposomal nucleic acid delivery systems.

Due to their size and tailorable physicochemical properties, nanomaterials are an emerging class of structures utilized in biomedical applications. There are now many prominent examples of nanomaterials being used to improve human health, in areas ranging from imaging and diagnostics to therapeutics and regenerative medicine. An overview of these examples reveals several common areas of synergy and future challenges. This Nano Focus discusses the current status and future potential of promising nanomaterials and their translation from the laboratory to the clinic, by highlighting a handful of successful examples.

•A photo responsive liposomal system for controlled release is proposed and synthesized.•With Calcein as a model drug, we evaluate the encapsulation efficiency and the release kinetic profile upon heat/light stimulation.•We further characterized their size, morphology, phase transition temperature and stability.•The mechanism behind the photo-triggered release relies on liposome membrane disruption by microbubble cavitation upon laser treatment.Drug-carriers, capable of releasing the drug at the target sites upon external stimuli, are attractive for theranostic applications. In recent years, photo-responsive nanoparticles (NPs) have received considerable attention because of their potentials in providing spatial, temporal, and dosage control over the drug release. However, most of the relevant technologies are still in the process of development and are unprocurable by the clinics. Here, we demonstrated facile fabrication of these photo-responsive NPs by loading hydrophilic gold NPs within thermo-responsive liposomes. Calcein was used as a model drug to evaluate the encapsulation efficiency and the release kinetic profile upon heat/light stimulation. Furthermore, we characterized their size, morphology, phase transition temperature and stability. Finally, we demonstrated that this photo-triggered release might be due to the membrane disruption caused by microbubble cavitation.

Correction for ‘Fluorescence quenching between unbonded graphene quantum dots and gold nanoparticles upon simple mixing’ by Yi Liu et al., RSC Adv., 2014, 4, 35673–35677.

Fluorescence quenching is an interesting phenomenon that has been widely utilized in developing fluorescence-based sensors. However, most of the research focuses on the quencher and fluorophore in the bonded states. The fluorescence quenching between two unbonded nanostructures has been rarely studied. In this work, we observed and studied the fluorescence-quenching phenomenon between the unbonded gold nanoparticles (Au NPs) and graphene quantum dots (GQDs) upon simple mixing. We observed that the fluorescence of GQDs gradually decreased with the increase of Au NP concentration. This fluorescence quenching between unbonded GQDs and Au NPs obeys the nonlinear form of the Stern–Volmer model, which suggests that the process contains both static and dynamic quenching.

Magnetic nanoparticles (MNPs) based on iron oxide, especially magnetite (Fe3O4), have been explored as sensitive probes for magnetic resonance imaging and therapeutic applications. Such application potentials plus the need to achieve high efficiency and sensitivity have motivated the search for new forms of superparamagnetic NPs with additional chemical and physical functionalities. This review summarizes the latest development of high moment MNPs, multifunctional MNPs, and porous hollow MNPs for biosensing, molecular imaging, and drug delivery applications.Download high-res image (213KB)Download full-size image

Regenerative medicine, which replaces or regenerates human cells, tissues or organs, to restore or establish normal function, is one of the fastest-evolving interdisciplinary fields in healthcare. Over 200 regenerative medicine products, including cell-based therapies, tissue-engineered biomaterials, scaffolds and implantable devices, have been used in clinical development for diseases such as diabetes and inflammatory and immune diseases. To facilitate the translation of regenerative medicine from research to clinic, nanotechnology, especially magnetic nanoparticles have attracted extensive attention due to their unique optical, electrical, and magnetic properties and specific dimensions. In this review paper, we intend to summarize current advances, challenges, and future opportunities of magnetic nanoparticles for regenerative medicine.

Stem cell tracking can reveal the underlying biological processes of stem-cell-based therapies such as the migration and biodistribution of human mesenchymal stem cells (hMSCs) in cancer therapy. Nanoparticle-based contrast agents offer unprecedented opportunities for achieving this goal due to their unique and tunable imaging capabilities. However, most nanoparticles are still in the process of development due to challenges such as retention time and safety issues, and are inaccessible to most researchers. In this article, we investigate the potential application of core–shell fluorescent silica nanoparticles (i.e. C dots), which are commercially available and approved by the FDA for clinical trials. Specifically we demonstrate that 500 nm C dots have prolonged cellular retention (up to one month), minimal contrast agent transfer (at least three weeks) between cells in a co-culture Boyden chamber system, and minimal influence on the hMSC properties including viability, proliferation, differentiation, and tropism to tumor cells.

Assessment of intracellular mRNA expression is invaluable for understanding cellular signaling activities, identifying disease stages, and monitoring the gene expression pattern of therapeutic cells during their culture, expansion and/or differentiation process. Previous methods suffer from the need to disrupt the biological samples to perform polymerase chain reaction analysis which can be laborious, fragmented and destructive. Herein, we develop a mRNA nanosensor based on the sustained release of mRNA-specific molecular beacons (probes that fluoresce upon hybridization) from the biodegradable poly(D,L-lactide-co-glycolide) nanoparticles. Post cellular internalization, the particles gradually degrade and release the encapsulated probes which are initially weakly fluorescent. When the released probes meet and hybridize with target mRNA, they restore pre-quenched fluorescence. By virtue of quantifying the fluorescence intensity, we can estimate the cellular mRNA expression. As a case study, β-actin mRNA expression in mesenchymal stem cells cultured on a 3D matrix was monitored and compared with those cultured on a 2D plate for one week. Critically, the observed expression profile shows a great correlation with the established quantitative polymerase chain reaction analysis.

Tissue adhesives have emerged as alternatives to suturing and stapling in the treatment of reconnection of injured tissues. They can be accurately applied to the regions of body that are not easy to access in a minimally invasive way without a high level of training. Recently, it was demonstrated that nanoparticles can directly glue hydrogels or tissues without the need for in situ polymerization or crosslinking. For example, silica nanoparticles can serve as connectors between tissues and exhibit adhesion even in the presence of blood. This work reports the adhesive effect of two antimicrobial nanoparticles, i.e. titanium dioxide and zinc oxide nanoparticles, between hydrogels, hydrogel/polymer, and liver tissues. These two nanoparticles exhibit comparable or even better adhesive effects in comparison to silica nanoparticles. In a skin wound mouse model, zinc oxide nanoparticles achieve successful wound closure and aesthetic wound healing, suggesting their capability as an effective antimicrobial tissue adhesive.