Abstract
To date, the role of elasticity in drug delivery remains elusive due to the inability to measure microscale mechanics and alter rheology without affecting chemistry. Herein, we describe the in vitro cellular uptake and in vivo tumor uptake of nanolipogels (NLGs). NLGs are composed of identical lipid bilayers encapsulating an alginate core, with tunable elasticity. The elasticity of NLGs was evaluated by atomic force microscopy, which demonstrated that they exhibit Young’s moduli ranging from 45 ± 9 to 19,000 ± 5 kPa. Neoplastic and non-neoplastic cells exhibited significantly greater uptake of soft NLGs (Young’s modulus <1.6 MPa) relative to their elastic counterparts (Young’s modulus >13.8 MPa). In an orthotopic breast tumor model, soft NLGs accumulated significantly more in tumors, whereas elastic NLGs preferentially accumulated in the liver. Our findings demonstrate that particle elasticity directs tumor accumulation, suggesting that it may be a design parameter to enhance tumor delivery efficiency.
Highlights
To date, the role of elasticity in drug delivery remains elusive due to the inability to measure microscale mechanics and alter rheology without affecting chemistry
Nanoliposomes (NLPs) and nanoparticles (NPs) are two major classes of drug delivery systems used to control drug distribution and release[1]. These two systems may be engineered with identical size, shape, and surface charge; there exists between them characteristic differences in their architecture and particle elasticity
We further evaluated the influence of particle concentration (Fig. 2g), serum (Fig. 2h), and incubation time (Supplementary Fig. 2) on particle elasticity-mediated cellular uptake
Summary
The role of elasticity in drug delivery remains elusive due to the inability to measure microscale mechanics and alter rheology without affecting chemistry. Nanoliposomes (NLPs) and nanoparticles (NPs) are two major classes of drug delivery systems used to control drug distribution and release[1] These two systems may be engineered with identical size, shape, and surface charge; there exists between them characteristic differences in their architecture and particle elasticity. NLPs have an aqueous core encapsulated within a lipid bilayer, whereas NPs are solid structures composed of amorphous and/or crystalline polymers or inorganic materials Both NLPs and NPs exhibit size-dependent properties, significantly different from the properties of the bulk material. Particle elasticity is hypothesized to alter cellular uptake and tumor accumulation due to its ability to bind cell surface receptors and squeeze through pores[12,13,14,15,16,17,18,19]. Particle elasticity is not yet a design parameter to enhance tumor delivery efficiency
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