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

Abstract

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.

Effect of the disulfide bond and polyethylene glycol on the degradation and biophysicochemical properties of polyurethane micelles

“…4B, the size of G8C50mE1900 and G8C50mE5000 remained unchanged, but the micellar diameter with short or without the mPEG chain increased over 10 times, due to inappropriate hydrophilic and hydrophobic proportions in segments and GQA groups disturbed micellar stabilization in PBS solution. 30 While the micelles G8C0mE1900, G8C50mE1900, and G8C70mE1900 are stable in PBS solution within 24 h of incubation, indicating that the CYSD group does not affect the stability of micelles under the simulative physiological conditions.…”

“…29 In addition, the alkyl chain length of GQA and molecular weight of mPEG have a large effect on the surface charge exposure, stability, and cell uptake properties of polymeric micelles. 30 The basic understanding of the interaction has been established between hydrophilic mPEG, which is widely used as a hydrated outer shell and GQA, which significantly improves cell internalization. However, it is still insufficient to guide the design and fabrication of multifunction nanoformulations.…”

Amphiphilic Graft Copolymers of Quaternized Alginate-g-Polytetrahydrofuran for Anti-protein Surfaces, Curcumin Carriers, and Antibacterial Materials

“…Based on the above experimental results, the influence of the graft copolymer structure on its properties is further discussed. Cationic quaternary ammonium is regarded as a cell internalization promoter to improve the cellular uptake of drug nanocarriers and enhance the hydrophobic drug loading capacity. − The long hydrophobic alkyl chains are contributed to the drug loading rate and cell membrane permeability, leading to efficient drug internalization by the cancer cells . Furthermore, the growing solid tumor shows an increase in vascular permeability with a pore size of 200–780 nm and polymer-based nanoparticles with a size of 10–1000 nm can be applied as diagnostic or therapeutic agents .…”

Stable, Bioresponsive, and Macrophage-Evading Polyurethane Micelles Containing an Anionic Tripeptide Chain Extender

“…In our previous study, we have reported the construction of several multifunctional polyurethane micelles as drug delivery systems. 36−38 We have demonstrated that the cationic polyurethane micelles carried out an effective internalization. 39,40 However, the positive surface charge of polyurethane micelles could accelerate the elimination by macrophages and increase the accumulation in the liver, spleen, and kidney.…”

“…In our previous study, we have reported the construction of several multifunctional polyurethane micelles as drug delivery systems. − We have demonstrated that the cationic polyurethane micelles carried out an effective internalization. , However, the positive surface charge of polyurethane micelles could accelerate the elimination by macrophages and increase the accumulation in the liver, spleen, and kidney. ,− In this work, we aim to develop anionic polyurethane micelles containing the hydrophilic PEG chain and disulfide bond, which can minimize the recognition and elimination by RES owing to the electrostatic repulsion and hydrophilic shell protection and respond to the redox potentials in tumor cells, to improve the biodistribution and maintain the therapeutic effect of polymeric micelles.…”