Combination of optogenetics and pharmacology represents a unique approach to dissect neural circuitry with high specificity and versatility. However, conventional tools available to perform these experiments, such as optical fibers and metal cannula, are limited due to their tethered operation and lack of biomechanical compatibility. To address these issues, a miniaturized, battery-free, soft optofluidic system that can provide wireless drug delivery and optical stimulation for spatiotemporal control of the targeted neural circuit in freely behaving animals is reported. The device integrates microscale inorganic light-emitting diodes and microfluidic drug delivery systems with a tiny stretchable multichannel radiofrequency antenna, which not only eliminates the need for bulky batteries but also offers fully wireless, independent control of light and fluid delivery. This design enables a miniature (125 mm3), lightweight (220 mg), soft, and flexible platform, thus facilitating seamless implantation and operation in the body without causing disturbance of naturalistic behavior. The proof-of-principle experiments and analytical studies validate the feasibility and reliability of the fully implantable optofluidic systems for use in freely moving animals, demonstrating its potential for wireless in vivo pharmacology and optogenetics.
We report a modular strategy for the solubilization and protection of hydrophobic transition metal catalysts using the hydrophobic pockets of water soluble gold nanoparticles. Beside preserving original catalyst activity, this encapsulation strategy provides a protective environment for the hydrophobic catalyst and brings reusability. This system provides a versatile platform for the encapsulation of different hydrophobic transition metal catalysts, allowing a wide range of catalysis in water while uniting the advantages of homogeneous and heterogeneous catalysis in the same system.
Chemotherapy is the mainstream treatment of anaplastic large cell lymphoma (ALCL). However, chemotherapy can cause severe adverse effects in patients because it is not ALCL-specific. In this study, we developed a multifunctional aptamer-nanomedicine (Apt-NMed) achieving targeted chemotherapy and gene therapy of ALCL. Apt-NMed was formulated by self-assembly of synthetic oligonucleotides containing CD30-specific aptamer and ALK-specific siRNA followed by self-loading of the chemotherapeutic drug doxorubicin (DOX). Apt-NMed exhibited a well-defined nanostructure (diameter 59 mm) and stability in human serum. Under aptamer guidance, Apt-NMed specifically bound and internalized targeted ALCL cells. Intracellular delivery of Apt-NMed triggered rapid DOX release for targeted ALCL chemotherapy and intracellular delivery of the ALK-specific siRNA induced ALK oncogene silencing, resulting in combined therapeutic effects. Animal model studies revealed that upon systemic administration, Apt-NMed specifically targeted and selectively accumulated in ALCL tumor site, but did not react with off-target tumors in the same xenograft mouse. Importantly, Apt-NMed not only induced significantly higher inhibition in ALCL tumor growth, but also caused fewer or no side effects in treated mice compared to free DOX. Moreover, Apt-NMed treatment markedly improved survival rate of treated mice, opening a new avenue for precision treatment of ALCL.
The accumulation and formation ofβ-amyloid (Aβ) plaques in the brain are distinctive pathological hallmarks of Alzheimer’s disease (AD). Designing nanoparticle (NP) contrast agents capable of binding with Aβhighly selectively can potentially facilitate early detection of AD. However, a significant obstacle is the blood brain barrier (BBB), which can preclude the entrance of NPs into the brain for Aβbinding. In this work, bovine serum albumin (BSA) coated NPs are decorated with sialic acid (NP-BSAx-Sia) to overcome the challenges in Aβimaging in vivo. The NP-BSAx-Sia is biocompatible with high magnetic relaxivities, suggesting that they are suitable contrast agents for magnetic resonance imaging (MRI). The NP-BSAx-Sia binds with Aβin a sialic acid dependent manner with high selectivities toward Aβdeposited on brains and cross the BBB in an in vitro model. The abilities of these NPs to detect Aβin vivo in human AD transgenic mice by MRI are evaluated without the need to coinject mannitol to increase BBB permeability.T2*-weighted MRI shows that Aβplaques in mouse brains can be detected as aided by NPBSAx- Sia, which is confirmed by histological analysis. Thus, NP-BSAx-Sia is a promising new tool for noninvasive in vivo detection of Aβplaques.
Liposomal spherical nucleic acids (LSNAs) are an attractive therapeutic platform for gene regulation and immunomodulation due to their biocompatibility, chemically tunable structures, and ability to enter cells rapidly without the need for ancillary transfection agents. Such structures consist of small (<100 nm) liposomal cores functionalized with a dense, highly oriented nucleic acid shell, both of which are key components in facilitating their biological activity. Here, the properties of LSNAs synthesized using conventional methods, anchoring cholesterol terminated oligonucleotides into a liposomal core, are compared to LSNAs made by directly modifying the surface of a liposomal core containing azide-functionalized lipids with dibenzocyclooctyl-terminated oligonucleotides. The surface densities of the oligonucleotides are measured for both types of LSNAs, with the lipid-modified structures having approximately twice the oligonucleotide surface coverage. The stabilities and cellular uptake properties of these structures are also evaluated. The higher density, lipid-functionalized structures are markedly more stable than conventional cholesterol-based structures in the presence of other unmodified liposomes and serum proteins as evidenced by fluorescence assays. Significantly, this new form of LSNA exhibits more rapid cellular uptake and increased sequence-specific toll-like receptor activation in immune reporter cell lines, making it a promising candidate for immunotherapy.
Stimuli-responsive porous polymer materials have promising biomedical application due to their ability to trap and release biomacromolecules. In this work, a class of highly porous electrospun fibers is designed using polylactide as the polymer matrix and poly(ethylene oxide) as a porogen. Carbon nanotubes (CNTs) with different concentrations are further impregnated onto the fibers to achieve self-sealing functionality induced by photothermal conversion upon light irradiation. The fibers with 0.4 mg mL?1of CNTs exhibit the optimum encapsulation efficiency of model biomacromolecules such as dextran, bovine serum albumin, and nucleic acids, although their photothermal conversion ability is slightly lower than the fibers with 0.8 mg mL?1of CNTs. Interestingly, reversible reopening of the surface pores is accomplished with the degradation of PLA, affording a further possibility for sustained release of biomacromolecules after encapsulation. Effects of CNT loading on fiber morphology, structure, thermal/mechanical properties, degradation, and cell viability are also investigated. This novel class of porous electrospun fibers with self-sealing capability has great potential to serve as an enabling strategy for trapping/release of biomacromolecules with promising applications in, for example, preventing inflammatory diseases by scavenging cytokines from interstitial body fluids.
Cellulose is the most abundant natural polymer on earth, providing a sustainable green resource that is renewable, degradable, biocompatible and cost effective. Recently, nanocellulose-based mesoporous structure, flexible thin films, fibers, and networks are increasingly developed and used in photovoltaic devices, energy storage systems, mechanical energy harvesters, and catalysts components, showing tremendous materials science value and application potential in many energy-related fields. In this review article, we review the most recent advancements of processing, integration and application of cellulose nanomaterials in the areas of solar energy harvesting, energy storage, and mechanical energy harvesting. For solar energy harvesting, promising applications of cellulose-based nanostructures for both solar cells and photoelectrochemical electrodes development are reviewed, and their morphology-related merits are discussed. For energy storage, our discussion is primarily focused on the applications of cellulose-based nanomateriales in lithium ion batteries, including electrodes (e.g. active materials, binders and structural support), electrolytes, and separators. Applications of cellulose nanomaterials in supercapacitors are also overviewed briefly. For mechanical energy harvesting, we review the most recent technology evolution of cellulose-based triboelectric nanogenerators, from fundamental property tuning to practical implementations. At last, the future research potential and opportunities of cellulose nanomaterials as a new energy material are commented.
A common cause of local tumor recurrence in brain tumor surgery results from incomplete surgical resection. Adjunctive technologies meant to facilitate gross total resection have had limited efficacy to date. Contrast agents used to delineate tumors pre-operatively cannot be easily or accurately used in the real-time operative setting. Although multimodal imaging contrast agents have been developed to help the surgeon discern tumor from normal tissue in the operating room, these contrast agents are not readily translatable. We have developed a novel contrast agent comprised solely of two FDA-approved components, indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) nanoparticles - with no additional amphiphiles or carrier-materials, to enable pre-operative detection by MRI and intraoperative photoacoustic (PA) imaging. The encapsulation efficiency of both ICG and SPIO within the formulated clusters is ~100% and the total ICG payload is 20–30% of the total weight (ICG + SPIO). The ICG-SPIO clusters are stable in physiologic conditions, can be taken up within tumors by enhanced permeability and retention, and are detectable by MRI. In a pre-clinical surgical resection model in mice following injection of ICG-SPIO clusters, animals undergoing PA-guided surgery demonstrated increased progression-free survival compared to animals undergoing microscopic surgery.