CaCO_(3)-encircled hollow CuS nanovehicles to suppress cervical cancer through enhanced calcium overload-triggered mitochondria damage

Cervical cancer stands is a formidablemalignancy that poses a significant threat towomen’s health.Calcium overload,a minimally invasive tumor treatment,aims to accumulate an excessive concentration of Ca^(2+)within mitochondria,triggering apoptosis.Copper sulfide(CuS)represents a photothermal mediator for tumor hyperthermia.However,relying solely on thermotherapy often proves insufficient in controlling tumor growth.Curcumin(CUR),an herbal compound with anti-cancer properties,inhibits the efflux of exogenous Ca^(2+)while promoting its excretion from the endoplasmic reticulum into the cytoplasm.To harness these therapeutic modalities,we have developed a nanoplatform that incorporates hollow CuS nanoparticles(NPs)adorned with multiple CaCO_(3) particles and internally loaded with CUR.This nanocomposite exhibits high uptake and easy escape from lysosomes,along with the degradation of surrounding CaCO3,provoking the generation of abundant exogenous Ca^(2+)in situ,ultimately damaging the mitochondria of diseased cells.Impressively,under laser excitation,the CuS NPs demonstrate a photothermal effect that accelerates the degradation of CaCO_(3),synergistically enhancing the antitumor effect through photothermal therapy.Additionally,fluorescence imaging reveals the distribution of these nanovehicles in vivo,indicating their effective accumulation at the tumor site.This nanoplatform shows promising outcomes for tumor-targeting and the effective treatment in a murine model of cervical cancer,achieved through cascade enhancement of calcium overload-based dual therapy.

Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery,as demonstrated by the approval of patisiran for amyloidosis therapy in 2018.To illuminate the unique superiority of lipid nanovehicles in RNA delivery,in this review,we first introduce various RNA therapeutics,describe systemic delivery barriers,and explain the lipid components and methods used for lipid nanovehicle preparation.Then,we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery.Finally,the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed.Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery,inspiring the development of more high-performance RNA lipid nanovesicles in the future.

Responsive MXene nanovehicles deliver CRISPR/Cas12a for boolean logic-controlled gene editing

Programmable and precise regulation of genetic information is crucial in bioengineering and biomedicine;however, it remains challenging to implement this objective. Here we deployed DNA-functionalized MXenes as a smart delivery system for spatiotemporally controllable genome editing. The MXene nanovehicles rationally integrated photothermal effect with nucleic acid strand displacement reaction, thereby allowing for the binary logic gate-controlled release of Cas ribonucleoprotein complexes in response to different input patterns of NIR light and nucleic acids. This system was highly programmable and could be harnessed to construct 2-input(AND, OR, and N-IMPLY) and 3-input(AND/OR and N-IMPLY/OR) logic gates for precise gene editing in mammalian cells. Moreover, an AND logic gate-controlled delivery system achieved selective induction of tumor cell death in a xenograft mice model using tissue-penetrating NIR light and cancer-relevant microRNA as the inputting cues.Therefore, the MXene nanovehicles adopted both the external and endogenous signals as the stimuli to precisely control gene editing under logic computation, presenting a helpful strategy for therapeutic genome editing.

Nanotrains and Self-Assembled Two-Dimensional Arrays Built from Carboranes Linked by Hydrogen Bonding of Dipyridones

The strong hydrogen bonding ability of 2-pyridones were exploited to build nanotrains on surfaces.Carborane wheels on axles difunctionalized with 2-pyridone hydrogen bonding units were synthesized and displayed spontaneous formation of linear nanotrains by self-assembly on SiO_(2)or mica surfaces.Imaging using atomic force microscopy confi rmed linear formations with lengths up to 5μm and heights within the range of the molecular height of the carborance-tipped axles.