Computational Study on the Regulatory Mechanism of Cell Membrane Wrapping on Liposomes by Embedded Bowl-like Nanostructures for Drug Delivery

Abstract

Controlling the nanoparticle's (NP) ability to facilitate cell uptake is particularly desirable for biomedical applications, such as drug delivery. Despite growing evidence highlighting the pivotal role of mechanical properties in biological performances of NPs, consensus regarding how stiffness regulates the cell entry of NPs is lacking. Here, we design and elucidate cell membrane wrapping on soft liposomes in which rigid bowl-like nanostructures are embedded. Compared with pure liposomes, which are often partially wrapped by a membrane due to the high energy barrier associated with the oblate deformation, embedded nanobowls provide physical support to promote wrapping by increasing the liposome rigidity. Through correlating liposome deformation, invagination, and nanobowl orientation, two distinct pathways of cell membrane wrapping on nanobowl-supported liposomes are identified. Different from alternative methods of tuning the rigidity of NPs uniformly, the nanobowl-supported liposome is characterized by mechanical heterogeneity and nanobowl rotation, which correlates with liposome deformation to promote endocytic wrapping. Once the nanobowl's rotation is restrained, wrapping turns out to be accomplished via membrane protrusion rather than invagination, and the wrapped liposome could be trapped with frustrated internalization and potential membrane perturbation. Following this principle, moderate decreases of the nanobowl size and adhesive strength with the liposome can facilitate the nanobowl's rotation to promote cell uptake. These results are expected to improve our ability to develop better NPs for enhanced drug delivery.

Regulation of Nanoliposome Rigidity and Bioavailability of Oligomeric Proanthocyanidin with Phytosterols Containing Different C3 Branches

“…Studies have shown that the cellular uptake efficiency of positively charged nanoliposomes was affected by their rigidity when they are taken up by cells through endocytosis. , Therefore, DPPC nanoliposomes might be taken up by Caco-2 cells through endocytosis. Soft nanoliposomes are believed to have a low endocytosis efficiency because they are effortless to deform during endocytosis. , This increases the contact area between the nanoliposome and the cell membrane, requiring the cell membrane to increase the energy to engulf the liposome and a greater adhesion to complete the encapsulation of the membrane. , Endocytosis of soft liposomes is also hindered by uneven ligand distribution . The same situation was found by Dai et al, where the most rigid liposome (Lip 4) showed the greatest degree of cellular uptake.…”

“…Soft nanoliposomes are believed to have a low endocytosis efficiency because they are effortless to deform during endocytosis. 36,63 This increases the contact area between the nanoliposome and the cell membrane, requiring the cell membrane to increase the energy to engulf the liposome and a greater adhesion to complete the encapsulation of the membrane. 15,64 Endocytosis of soft liposomes is also hindered by uneven ligand distribution.…”

Polymeric Bowl‐Shaped Nanoparticles: Hollow Structures with a Large Opening on the Surface

“…[ 141–143 ] Typically, the anisotropic structure of BNPs promotes endocytosis by cancer cells, proved by either experimental or computational studies. [ 144,145 ] For instance, Wu et al. [ 141 ] prepared ruthenium (Ru) containing BNPs self‐assembled from a novel Ru containing triblock copolymer, acting as a photoactivated polymetallodrug for combined photodynamic therapy and photochemotherapy in vivo, as shown in Figure .…”

Manipulation of Bowl-Shaped Nanoparticles Self-Assembled from a Bipyridine Pendant Containing Homopolymer

“…Polymer self-assembly has been widely used to prepare a large variety of nanomaterials, including micelles, vesicles, cylinders, and lamellaes, showing significant potentials in drug delivery, antimicrobial, anticancer and catalysis, etc. Among them, bowl-shaped nanoparticles (BNPs) have drawn wide attention due to their anisotropic structure and a large opening on the surface, promoting their applications in smart carrier especially for large-sized cargoes, cancer therapy, water remediation, and nanomotors . The recent advances of polymeric BNPs have been summarized in our recent review article .…”