Nanodelivery Systems for Topical Management of Skin Disorders.

Topical drug delivery has inherent advantages over other administration routes. However, the existence of stratum corneum limits the diffusion to small and lipophilic drugs. Fortunately, the advancement of nanotechnology brings along opportunities to address this challenge. Taking the unique features in size and surface chemistry, nanocarriers such as liposomes, polymeric nanoparticles, gold nanoparticles, and framework nucleic acids have been used to bring drugs across the skin barrier to epidermis and dermis layers. This article reviews the development of these formulations and focuses on their applications in the treatment of skin disorders such as acne, skin inflammation, skin infection, and wound healing. Existing hurdles and further developments are also discussed.

Nanosensors for Continuous and Noninvasive Monitoring of Mesenchymal Stem Cell Osteogenic Differentiation.

Assessing mesenchymal stem cell (MSC) differentiation status is crucial to verify therapeutic efficacy and optimize treatment procedures. Currently, this involves destructive methods including antibody-based protein detection and polymerase chain reaction gene analysis, or laborious and technically challenging genetic reporters. Development of noninvasive methods for real-time differentiation status assessment can greatly benefit MSC-based therapies. This report introduces a nanoparticle-based sensing platform that encapsulates two molecular beacon (MB) probes within the same biodegradable polymeric nanoparticles. One MB targets housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal reference, while another detects alkaline phosphatase (ALP), a functional biomarker. Following internalization, MBs are gradually released as the nanoparticle degrades. GAPDH MBs provide a stable reference signal throughout the monitoring period (18 days) regardless of differentiation induction. Meanwhile, ALP mRNA undergoes well-defined dynamics with peak expression observed during early stages of osteogenic differentiation. By normalizing ALP-MB signal with GAPDH-MB, changes in ALP expression can be monitored, to noninvasively validate osteogenic differentiation. As proof-of-concept, a dual-colored nanosensor is applied to validate MSC osteogenesis on 2D culture and polycaprolactone films containing osteo-inductive tricalcium phospate.

Synergism of Water Shock and a Biocompatible Block Copolymer Potentiates the Antibacterial Activity of Graphene Oxide.

Graphene oxide (GO) is promising in the fight against pathogenic bacteria. However, the antibacterial activity of pristine GO is relatively low and concern over human cytotoxicity further limits its potential. This study demonstrates a general approach to address both issues. The developed approach synergistically combines the water shock treatment (i.e., a sudden decrease in environmental salinity) and the use of a biocompatible block copolymer (Pluronic F-127) as a synergist co-agent. Hypoosmotic stress induced by water shock makes gram-negative pathogens more susceptible to GO. Pluronic forms highly stable nanoassemblies with GO (Pluronic-GO) that can populate around bacterial envelopes favoring the interactions between GO and bacteria. The antibacterial activity of GO at a low concentration (50 µg mL(-1) ) increases from <30% to virtually complete killing (>99%) when complemented with water shock and Pluronic (5 mg mL(-1) ) at ≈2-2.5 h of exposure. Results suggest that the enhanced dispersion of GO and the osmotic pressure generated on bacterial envelopes by polymers together potentiate GO. Pluronic also significantly suppresses the toxicity of GO toward human fibroblast cells. Fundamentally, the results highlight the crucial role of physicochemical milieu in the antibacterial activity of GO. The demonstrated strategy has potentials for daily-life bacterial disinfection applications, as hypotonic Pluronic-GO mixture is both safe and effective.

Layer-by-Layer 3D Constructs of Fibroblasts in Hydrogel for Examining Transdermal Penetration Capability of Nanoparticles.

Nanoparticles are emerging transdermal delivery systems. Their size and surface properties determine their efficacy and efficiency to penetrate through the skin layers. This work utilizes three-dimensional (3D) bioprinting technology to generate a simplified artificial skin model to rapidly screen nanoparticles for their transdermal penetration ability. Specifically, this model is built through layer-by-layer alternate printing of blank collagen hydrogel and fibroblasts. Through controlling valve on-time, the spacing between printing lines could be accurately tuned, which could enable modulation of cell infiltration in the future. To confirm the effectiveness of this platform, a 3D construct with one layer of fibroblasts sandwiched between two layers of collagen hydrogel is used to screen silica nanoparticles with different surface charges for their penetration ability, with positively charged nanoparticles demonstrating deeper penetration, consistent with the observation from an existing study involving living skin tissue.

Near-infrared light-responsive liposomal contrast agent for photoacoustic imaging and drug release applications.

Photoacoustic imaging has become an emerging tool for theranostic applications. Not only does it help in

Fluorescent Poly(glycerol-co-sebacate) Acrylate Nanoparticles for Stem Cell Labeling and Longitudinal Tracking.

The stable presence of fluorophores within the biocompatible and biodegradable elastomer poly(glycerol-co-sebacate) acrylate (PGSA) is critical for monitoring the transplantation, performance, and degradation of the polymers in vivo. However, current methods such as physically entrapping the fluorophores in the polymer matrix or providing a fluorescent coating suffer from rapid leakage of fluorophores. Covalent conjugation of fluorophores with the polymers and the subsequent core-cross-linking are proposed here to address this challenge. Taking rhodamine as the model dye and PGSA nanoparticles (NPs) as the model platform, we successfully showed that the synthesized rhodamine-conjugated PGSA (PGSAR) NPs only released less than 30% rhodamine at day 28, whereas complete release of dye occurred for rhodamine-encapsulated PGSA (PGSA-p-R) NPs at day 7 and 57.49% rhodamine was released out for the un-cross-linked PGSAR NPs at day 28. More excitingly, PGSAR NPs showed a strong quantum yield enhancement (26.24-fold) of the fluorophores, which was due to the hydrophobic environment within PGSAR NPs and the restricted rotation of (6-diethylamino-3H-xanthen-3-ylidene) diethyl group in rhodamine after the conjugation and core-cross-linking. The stable presence of dye in the NPs and enhanced fluorescence allowed a longitudinal tracking of stem cells both in vitro and in vivo for at least 28 days.

Smart Magnetic Nanosensors Synthesized through Layer-by-Layer Deposition of Molecular Beacons for Noninvasive and Longitudinal Monitoring of Cellular mRNA.

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.