DNA nanostructures are promising drug carriers with their intrinsic biocompatibility, uniformity and versatility. However, rapid serum disintegration leads to low bioavailability at targeted sites following systemic administration, hindering their biomedical applications. Here we demonstrate transdermal delivery of framework nucleic acids (FNAs) through topical applications. By designing FNAs with distinct shapes and sizes, we interrogate their penetration on mice and human skin explant. Skin histology reveals size-dependent penetration, with FNAs ≤75 nm effectively reaching dermis layer. 17 nm-tetrahedral FNAs show greatest penetration to 350 µm from skin periphery. Importantly, structural integrity is maintained during the skin penetration. Employing a mouse melanoma model, topical application of doxorubicin-loaded FNAs accommodates ≥2-fold improvement in drug accumulation and tumor inhibition relative to topically-applied free doxorubicin, or doxorubicin loaded in liposomes and polymeric nanoparticles. Programmable penetration with minimal systemic biodistribution underlines FNA potential as localized transdermal drug delivery carriers.
Graphene materials (GMs), such as graphene, graphene oxide (GO), reduced GO (rGO), and graphene quantum dots (GQDs), are rapidly emerging as a new class of broad-spectrum antimicrobial agents. This report describes their state-of-the-art and potential future covering both fundamental aspects and biomedical applications. First, the current understanding of the antimicrobial mechanisms of GMs is illustrated, and the complex picture of underlying structure-property-activity relationships is sketched. Next, the different modes of utilization of antimicrobial GMs are explained, which include their use as colloidal dispersions, surface coatings, and photothermal/photodynamic therapy agents. Due to their practical relevance, the examples where GMs function as synergistic agents or release platforms for metal ions and/or antibiotic drugs are also discussed. Later, the applicability of GMs in the design of wound dressings, infection-protective coatings, and antibiotic-like formulations ("nanoantibiotics") is assessed. Notably, to support our assessments, the existing clinical applications of conventional carbon materials are also evaluated. Finally, the key hurdles of the field are highlighted, and several possible directions for future investigations are proposed. We hope that the roadmap provided here will encourage researchers to tackle remaining challenges toward clinical translation of promising research findings and help realize the potential of GMs in antimicrobial nanomedicine.
Early detection of skin diseases is imperative for their effective treatment. However, fluorescence molecular probes that allow this are rare. The first activatable near-infrared (NIR) fluorescent molecular probe is reported for sensitive imaging of keloid cells, skin cells from abnormal scar fibrous lesions. As keloid cells have high expression levels of fibroblast activation protein-alpha (FAPα), the probe (FNP1) is designed to have a caged NIR dye and a FAPα-cleavable peptide substrate linked by a self-immolative segment. FNP1 can quickly and specifically turn on its fluorescence at 710 nm by 45-fold in the presence of FAPα, allowing it to effectively recognize keloid cells from normal skin cells. Integration of FNP1 with a simple microneedle-assisted topical application enables sensitive detection of keloid cells in metabolically-active human skin tissue with a theoretical limit of detection down to 20 000 cells.
The focus of drug delivery is shifting toward smart drug carriers that release the cargo in response to a change in the microenvironment due to an internal or external trigger. As the most clinically successful nanosystem, liposomes naturally come under the spotlight of this trend. This review summarizes the latest development about the design and construction of photo-responsive liposomes with gold nanoparticles for the controlled drug release. Alongside, we overview the mechanism involved in this process and the representative applications.
Transdermal delivery of therapeutic biomolecules (including peptides) can avoid enzymatic digestion that occurs in the oral route. (Polyethylene glycol) diacrylate (PEGDA)‐based microneedles, with good biocompatibility, are easily fabricated through photo‐polymerization with a precisely controlled structure. It has successfully been used for the transdermal delivery of small molecule drugs such as 5‐fluorouracil. However, the delivery of peptide‐based therapeutics using this platform is seldom reported. This is because of the potential damage to the peptide during the photo‐polymerization process of PEGDA. Herein, we introduce a method to load PEGDA microneedles with peptides without compromising peptide potency. Using gap junction inhibitor (Gap 26) as an example, the peptide was loaded into PEGDA microneedles through the swelling effect of PEGDA in the aqueous solution. The peptide‐loaded microneedles were applied to a keloid scar model and exhibited inhibition expression of collagen I, a predominant marker of keloid scar, demonstrating its potential therapeutic effects.
Nanoparticles are increasingly popular choices for labeling and tracking cells in biomedical applications such as cell therapy. However, all current types of nanoparticles fail to provide real-time, noninvasive monitoring of cell status and functions while often generating false positive signals. Herein, a nanosensor platform to track the real-time expression of specific biomarkers that correlate with cell status and functions is reported. Nanosensors are synthesized by encapsulating various sensor molecules within biodegradable polymeric nanoparticles. Upon intracellular entry, nanosensors reside within the cell cytoplasm, serving as a depot to continuously release sensor molecules for up to 30 days. In the absence of the target biomarkers, the released sensor molecules remain ‘Off’. When the biomarker(s) is expressed, a detectable signal is generated (On). As a proof-of-concept, three nanosensor formulations were synthesized to monitor cell viability, secretion of nitric oxide, and β-actin mRNA expression.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.