Albumin-Modified Cationic Nanocarriers To Potentially Create a New Platform for Drug Delivery Systems.

Cationic nanocarriers have emerged as promising nanoparticle systems for the effective delivery of nucleic acid and anticancer drugs to cancer cells. A positive charge is desirable for promoting cell internalization, whereas it also causes some adverse effects, such as toxicity and rapid clearance by mononuclear phagocytic systems. Herein, a new strategy of modifying cationic polymer micelles with albumin forming a protein corona to improve the surface physiochemical properties is reported. The corona with a monolayer or a multilayer was constructed depending on the albumin concentration, and the proteins would denature in different degrees due to the interaction with the surface of cationic micelles. It is demonstrated that multilayer albumin corona is beneficial to prevent macrophage uptake, increase accumulation in tumor tissues, and reduce toxic side effects to normal tissues. Our work provides a promising method to modify the cationic nanoplatform by optimizing the biosecurity and bioavailability for potential application in drug delivery.

Macrophage Polarization in Response to Varying Pore Sizes of 3D Polyurethane Scaffolds.

Activated macrophages dominate the progression of foreign-body response (FBR) and may be in a bimodal state, which determines the fate of biomaterials postimplantation. The purpose of this study was to investigate the phenotypic profile of macrophages polarized by waterborne biodegradable polyurethane (WBPU) scaffolds with different pore diameters (PU8, PU12, and PU16) both in vitro and in vivo. The results demonstrated that WBPU scaffolds with smaller pore sizes promoted the polarization of RAW 264.7 cells towards an M1 phenotypic profile at the early stage (24 and 48 h of in vitro cultivation), indicating a pro-inflammatory response. After being implanted subcutaneously, however, the WBPU scaffolds recruited more macrophages over time and polarized them towards an M2 phenotype on Day 3 and 14, presenting an anti-inflammatory response and tissue repair. When the internal pores were filled up (on Day 30 of implantation), the interaction between the scaffolds and macrophages decreased, indicating an endpoint of tissue repair. In general, WBPU scaffolds with tunable internal pore sizes have potential application prospects in the field of tissue engineering.

Understanding the effect of alkyl chains of gemini cations on the physicochemical and cellular properties of polyurethane micelles.

Cationic gemini quaternary ammonium (GQA) has been used as a cell internalization promoter to improve the permeability of the cell membrane and enhance the cellular uptake. However, the effect of the alkyl chain length on the cellular properties of nanocarriers has not been elucidated yet. In this study, we developed a series of polyurethane micelles containing GQAs with various alkyl chain lengths. The alteration of the gemini alkyl chain length was found to change the distribution of GQA surfactants in the micellar structure and affect the surface charge exposure, stability, and the protein absorption properties of nanocarriers. Moreover, we also clarified the role of the alkyl chain length in tumor cell internalization and macrophage uptake of polyurethane micelles. This work provides a new understanding on the effect of the GQA alkyl chain length on the physicochemical and biological properties of nanomedicines, and offers guidance on the rational design of effective drug delivery systems where the issue of functional group exposure at the micellar surface should be considered.