Cell membrane-coated mesoporous silica nanorods overcome sequential drug delivery barriers against colorectal cancer

Local delivery of nanomedicines holds therapeutic promise for colorectal cancer(CRC).However,it presents tremendous challenges due to the existence of multiple physiological barriers,especially intracellular obstacles,including intracellular trafficking,subcellular accumulation,and drug release.Herein,we report a multifunctional nanoparticle(CMSNR)by wrapping the mesoporous silica nanorod with cell membrane derived from CRC cells for improved chemotherapy.Compared with their naked counterparts,the cell membrane endowed CMSNR with homotypic targeting and improved cellular uptake capacities.Due to the rod-like shape,CMSNR achieved superior colorectal mucus permeability,enhanced tumor accumulation,and boosted cellular uptake than their spherical counterparts.Moreover,the internalized CMSNR underwent robust intracellular trafficking and gained augmented motility toward the nucleus,leading to efficient perinuclear accumulation and a subsequent 5.6-fold higher nuclear accumulation of loaded drug than that of nanospheres.In the orthotopic colorectal tumor-bearing nude mice,rectally administrated mefuparib hydrochloride(MPH)-loaded CMSNR traversed the colorectal mucus,penetrated the tumor tissue,and successfully aggregated in the perinuclear region of cancer cells,thus exhibiting significantly improved antitumor outcomes.Our findings highlight the shape-based design of cell membranecoated nanoparticles that can address sequential drug delivery barriers has a promising future in cancer nanomedicine.

The complexation of insulin with sodium N-[8-(2-hydroxybenzoyl)amino]-caprylate for enhanced oral delivery:Effects of concentration, ratio, and pH

Permeation enhancers(PEs),such as N-[8-(2-hydroxybenzoyl)amino]-caprylate(SNAC),have been reported to improve the oral absorption of various macromolecules.However,the bioavailabilities of these formulations are quite low and variable due to the influences of enzymes,pH and other gastrointestinal barriers.In this study,we revealed that SNAC could interact with insulin to form tight complexes in a specific concentration(insulin≥ 40μg/mL)-,ratio(SNAC/insulin≥ 20:1)-and pH(≥ 6.8)-dependent manner,thus contributing to a significantly high efficacy of oral insulin delivery.Specifically,absorption mechanism studies revealed that the SNAC/insulin complexes were internalized into the cells by passive diffusion and remained intact when transported in the cytosol.Furthermore,the complexes accelerated the exocytosis of insulin to the basolateral side,thereby enhancing its intestinal mucosal permeability.Eudragit;S100-entrapped SNAC/insulin microspheres were then prepared and exhibited an apparent permeability coefficient(P;) that was 6,6-fold higher than that of the insulin solution.In diabetic rats,hypoglycemic activity was sustained for more than 10 h after the microspheres were loaded into entericcoated capsules.Further pharmacokinetic studies revealed an approximately 6.3% oral bioavailability in both the fasted and fed states,indicating a negligible food effect.Collectively,this study provides insight into the interaction between PEs and payloads and presents an SNAC-based oral insulin delivery system that has high oral bioavailability and patient-friendly medication guidance.

One-pot synthesis of nuclear targeting carbon dots with high photoluminescence

Carbon dots(CDs) are novel fluorescent nanomaterials with good water solubility, high resistance to photobleaching and low toxicity. While, there are few studies elaborate on the relationship among reaction conditions, properties and applications of CDs. In this study, a series of CDs are synthesized through a one-pot hydrothermal method, and different reaction conditions are carried out to study the influencing factors of CDs properties. As a result, with the increase of temperature and reaction time, the particle size and zeta potential of CDs increased, the maximum emission wavelength red-shifted and the fluorescence quantum yield(QY) improved. Among them, CD3006 has good water solubility and highest QY of 81.4%, which is beneficial for its applications in bioimaging and ion detection. CD3006 is almost nontoxic in cells at a concentration of 500 μg/m L. In addition, the positive charged CD3006 shows nuclear targeting potential because of its combination with DNA through electrostatic interaction in nucleus. The properties of CDs can be greatly enhanced by controlling reaction conditions, and it provides great application prospects.