The highly acidic gastric environment creates a physiological barrier for using therapeutic drugs in the stomach. While proton pump inhibitors have been widely used for blocking acid-producing enzymes, this approach can cause various adverse effects. Herein, we report on a new microdevice, consisting of magnesium-based micromotors that can autonomously and temporally neutralize gastric acid through efficient chemical propulsion in the gastric fluid by rapidly depleting the localized protons. Coating these micromotors with a cargo-containing pH-responsive polymer layer leads to autonomous release of the encapsulated payload upon gastric-acid neutralization by the motors. Testing in a mouse model, the in vivo results demonstrate that these motors can safely and rapidly neutralize gastric acid and simultaneously release payload without causing noticeable acute toxicity or affecting the stomach function, with the normal stomach pH restored within 24 h post motor administration.
For
many medical treatments, particularly cancer, it is necessary
to develop a biocompatible microscale device that can carry a sufficient
amount of a drug and deliver it to target sites. While chemically
powered micromotors have been applied in live animal therapy, many
of them are difficult to biodegrade in vivo, which
might cause toxicity and side effects. Here, we report on a microdevice
that consists of a poly(aspartic acid) (PASP) microtube, a thin Fe
intermediate layer, and a core of Zn. This device can be propelled
using gastric acid as a fuel. After adsorption of doxorubicin onto
a PASP surface, the microrocket can carry drugs, magnetically locate
targets, permeate the gastric mucus gel layer, and increase drug retention
in the stomach without inducing an obvious toxic reaction. All materials
in the microrockets are biocompatible and biodegradable and can be
readily decomposed by the gastric acid or by proteases in the digestive
tract. Such microrockets, made with poly(amino acid)s, will extend
the practical biomedical applications of micro- and nanomotors.
Epigenetic modifications on DNA, especially on cytosine, play a critical role in regulating gene expression and genome stability. It is known that the levels of different cytosine derivatives are highly dynamic and are regulated by a variety of factors that act on the chromatin. Here we report an optical methodology based on hyperspectral dark-field imaging (HSDFI) using plasmonic nanoprobes to quantify the recently identified cytosine modifications on DNA in single cells. Gold (Au) and silver (Ag) nanoparticles (NPs) functionalized with specific antibodies were used as contrast-generating agents due to their strong Local Surface Plasmon Resonance (LSPR) properties. With this powerful platform we have revealed the spatial distribution and quantity of 5-carboxylcytosine (5caC) at the different stages in cell cycle, and demonstrated that 5caC was a stably inherited epigenetic mark. We have also shown that the regional density of 5caC on a single chromosome can be mapped due to the spectral sensitivity of the nanoprobes in relation to the inter-particle distance. Notably, HSDFI enables an efficient removal of the scattering noises from non-specifically aggregated nanoprobes, to improve accuracy in the quantification of different cytosine modifications in single cells. Further, by separating the LSPR fingerprints of AuNPs and AgNPs, multiplex detection of two cytosine modifications was also performed. Our results demonstrate HSDFI as a versatile platform for spatial and spectroscopic characterization of plasmonic nanoprobe-labeled nuclear targets at the single-cell level for quantitative epigenetic screening.
Photodynamic therapy (PDT) has been proven to be a minimally invasive and effective therapeutic strategy for cancer treatment. It can be used alone or as a complement to conventional cancer treatments, such as surgical debulking and chemotherapy. The mitochondrion is an attractive target for developing novel PDT agents, as it produces energy for cells and regulates apoptosis. Current strategy of mitochondria targeting is mainly focused on utilizing cationic photosensitizers that bind to the negatively charged mitochondria membrane. However, such an approach is lack of selectivity of tumor cells. To minimize the damage on healthy tissues and improve therapeutic efficacy, an alternative targeting strategy with high tumor specificity is in critical need. Herein, we report a tumor mitochondria-specific PDT agent, IR700DX-6T, which targets the 18 kDa mitochondrial translocator protein (TSPO). IR700DX-6T induced apoptotic cell death in TSPO-positive breast cancer cells (MDA-MB-231) but not TSPO-negative breast cancer cells (MCF-7). In vivo PDT study suggested that IR700DX-6T-mediated PDT significantly inhibited the growth of MDA-MB-231 tumors in a target-specific manner. These combined data suggest that this new TSPO-targeted photosensitizer has great potential in cancer treatment.
Rose bengal-grafted chitosan (RB-CHI), synthesized through dehydration between amino and carboxyl functional groups under mild conditions, was coated onto the outer layer of preformed biodegradable microcapsules consisting of sodium alginate and chitosan. The fabricated photosensitive microcapsules were characterized by optical microscopy, scanning electron microscopy, and confocal laser scanning microscopy. The assembled materials maintained intact spherical morphology and thus showed good ability to form thin films. Electron spin resonance spectroscopy allowed direct observation of the generation of singlet oxygen ((1)O(2)) from photosensitive microcapsules under light excitation at about 545 nm. Furthermore, with increasing light radiation, the content of (1)O(2) increased, as detected by a chemical probe. In vitro cellular toxicity assays showed that RB-CHI-coated photosensitive microcapsules exhibit good biocompatibility in darkness and high cytotoxicity after irradiation, and could provide new photoresponsive drug-delivery vehicles.
Islet transplantation is currently a promising treatment for type 1 diabetes mellitus. However, the foreign body reaction and retrieval difficulty often lead to transplantation failure and hinder the clinical application. To address these two challenges, we propose a balanced charged sodium alginate−polyethyleneimine−melanin (SA−PEI−Melanin) threadlike hydrogel with immune shielding and retrievable properties. The attractiveness of this study lies in that the introduction of melanin can stimulate insulin secretion, especially under near-infrared (NIR) irradiation. After demonstrating a good immune-shielding effect, we performed an in vivo transplantation experiment. The results showed that the blood glucose level in the SA−PEI−Melanin group was stably controlled below the diabetic blood glucose criterion, and this blood glucose level could be further adjusted after NIR irradiation. In addition, the evaluation after retrieving the SA−PEI−Melanin hydrogel indicated that the islets still maintained a normal physiological function, further proving its excellent immunological protection. This study provides a new approach for the accurate regulation of blood glucose in patients with type 1 diabetes mellitus and contributes to developing a promising transplant system to reconcile real-time and precise light-defined insulin secretion regulation.
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