Controlling the Biological Fate of Liposomal Spherical Nucleic Acids Using Tunable Polyethylene Glycol Shells

Abstract

Liposomal spherical nucleic acids (LSNAs) modified with polyethylene glycol (PEG) units are studied in an attempt to understand how the circulation time and biodistribution of the constructs can be manipulated. Specifically, the effect of (1) PEG molecular weight, (2) PEG shell stability, and (3) PEG modification method (PEG in both the core and shell versus PEG in the shell only) on LSNA blood circulation, biodistribution, and in vivo cell internalization in a syngeneic, orthotopic triple-negative breast cancer mouse model is studied. Generally, high PEG molecular weight extends blood circulation lifetime, and a more lipophilic anchor stabilizes the PEG shell and improves circulation and tumor accumulation but at the cost of cell uptake efficiency. The PEGylation strategy has a minor effect on in vitro properties of LSNAs but significantly alters in vivo cell uptake. For example, surface-only PEG in one design contributed to higher in vivo cell internalization than its counterpart with PEG both in the shell and core. Taken together, this work provides guidelines for designing LSNAs that exhibit maximal in vivo cancer cell uptake characteristics in the context of a breast cancer model.

Tuning Targeted Liposome Avidity to Cells via Lipid Phase Separation

“…A critical step in NP administration is interaction with a target cell surface. NPs are often engineered with two classes of surface modifications that affect this interaction: targeting moieties to promote NP interactions with specific receptors and cell types, and shielding polymers like polyethylene glycol (PEG) to increase in vivo circulation time and reduce the rate of biofouling in biological systems . While many intrinsic properties of NPs affect ligand-receptor binding, such as stiffness, − ligand mobility, − and surface roughness, an important, often less explored feature is the spatial presentation of conjugated ligands on the NP surface.…”

Enhancing functionalized liposome avidity to cells via lipid phase separation

“…NPs are often engineered with two classes of surface modifications that affect this interaction: (1) targeting moieties to promote NP interactions with specific receptors and cell types, 1 and (2) shielding polymers like polyethylene glycol (PEG) to increase in vivo circulation time and reduce the rate of in biological systems. 2 While many intrinsic properties of NPs affect ligand-receptor binding, such as stiffness, [3][4][5] ligand mobility, [6][7][8] and surface roughness, 9 an important, often less explored feature is the spatial presentation of conjugated ligands on the NP surface. Ligand density is an important parameter that controls bond multivalency when targeting a NP to a cellular receptor.…”

Nanoarchitectonics of Spherical Nucleic Acids with Biodegradable Polymer Cores: Synthesis and Evaluation

“…The first reported SNAs were thiolated oligonucleotides adsorbed onto the surface of gold nanoparticles (AuNP) [5]. Since then, a wide variety of inorganic and organic materials have been used to serve as a core, including silver [8,9], iron oxide [10], platinum [11], silica [12], quantum dots [13], liposomes [14][15][16][17], polymers [18][19][20][21][22], and proteins [23]. The unique chemical and physical properties of SNA in biological environments originate from the densely organized oligonucleotides on the nanoparticle surface, but the right choice of nanoparticles core plays an important role in the design of the nanosystems, as the core determines the sizes and shapes, as well as plasmonic, catalytic, and optical properties of the SNA.…”