Temperature- and rigidity-mediated rapid transport of lipid nanovesicles in hydrogels.

Lipid nanovesicles are widely present as transport vehicles in living organisms and can serve as efficient drug delivery vectors. It is known that the size and surface charge of nanovesicles can affect their diffusion behaviors in biological hydrogels such as mucus. However, how temperature effects, including those of both ambient temperature and phase transition temperature (Tm), influence vehicle transport across various biological barriers outside and inside the cell remains unclear. Here, we utilize a series of liposomes with different Tm as typical models of nanovesicles to examine their diffusion behavior in vitro in biological hydrogels. We observe that the liposomes gain optimal diffusivity when their Tm is around the ambient temperature, which signals a drastic change in the nanovesicle rigidity, and that liposomes with Tm around body temperature (i.e., ∼37 °C) exhibit enhanced cellular uptake in mucus-secreting epithelium and show significant improvement in oral insulin delivery efficacy in diabetic rats compared with those with higher or lower Tm Molecular-dynamics (MD) simulations and superresolution microscopy reveal a temperature- and rigidity-mediated rapid transport mechanism in which the liposomes frequently deform into an ellipsoidal shape near the phase transition temperature during diffusion in biological hydrogels. These findings enhance our understanding of the effect of temperature and rigidity on extracellular and intracellular functions of nanovesicles such as endosomes, exosomes, and argosomes, and suggest that matching Tm to ambient temperature could be a feasible way to design highly efficient nanovesicle-based drug delivery vectors.

Biological culture module for plant research from seed-to-seed on the Chinese Space Station.

The long-term cultivation of higher plants in space plays a substantial role in investigating the effects of microgravity on plant growth and development, acquiring valuable insights for developing a self-sustaining space life supporting system. The completion of the Chinese Space Station (CSS) provides us with a new permanent space experimental platform for long-term plant research in space. Biological Culture Module (GBCM), which was installed in the Wentian experimental Module of the CSS, was constructed with the objective of growing Arabidopsis thaliana and rice plants a full life cycle in space. The techniques of LED light control, gas regulation and water recovery have been developed for GBCM in which dry seeds of Arabidopsis and rice were set in root module of four culture chambers (CCs) and launched with Wentian module on July 24, 2022. These seeds were watered and germinated from July 28 and grew new seeds until November 26 within a duration of 120 days. To this end, both Arabidopsis and rice plants completed a full life cycle in microgravity on the CSS. As we know, this is the first space experiment achieving rice complete life cycle from seed-to-seed in space. This result demonstrates the possibility to cultivate the important food crop rice throughout its entire life cycle under the spaceflight environment and the technologies of GBCM have effectively supported the success of long-term plant culture experiments in space. These results can serve as invaluable references for constructing more expansive and intricate space plant cultivation systems in the future.

Protein Corona Liposomes Achieve Efficient Oral Insulin Delivery by Overcoming Mucus and Epithelial Barriers.

Oral delivery of peptide/protein drugs has attracted worldwide attention due to its good patient compliance and convenience of administration. Orally administered nanocarriers always encounter the rigorous defenses of the gastrointestinal tract, which mainly consist of mucus and epithelium barriers. However, diametrically opposite surface properties of nanocarriers are required for good mucus penetration and high epithelial uptake. Here, bovine serum albumin (BSA) is adsorbed to cationic liposomes (CLs) to form protein corona liposomes (PcCLs). The aim of using PcCLs is to conquer the mucus and epithelium barriers, eventually improving the oral bioavailability of insulin. Investigations using in vitro and in vivo experiments show that the uptake amounts and transepithelial permeability of PcCLs are 3.24- and 7.91-fold higher than that of free insulin, respectively. Further study of the behavior of PcCLs implies that BSA corona can be shed from PcCLs as they cross the mucus layer, which results in the exposure of CLs to improve the transepithelial transport. Intrajejunal administration of PcCLs in type I diabetic rats produces a remarkable hypoglycemic effect and increases the oral bioavailability up to 11.9%. All of these results imply that PcCLs may provide a new insight into the method for oral insulin delivery by overcoming the multiple barriers.