期刊
ACS NANO
卷 13, 期 7, 页码 7676-7689出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b01181
关键词
SUVs; liposome; chain length and saturation; membrane mechanics; vesicle rigidity; ECM penetration; tumor delivery
类别
资金
- National Natural Science Foundation of China [81803445, 81573571, 11872005, 81573378, 81773651]
- Excellent Academic Leaders Program of Shanghai [16XD1403500]
- Science and Technology Commission of Shanghai Municipality [17430741500]
- Shanghai Science and Technology Committee [18430721600]
- program of the Shanghai E-Research Institute of Bioactive Constituents in Traditional Chinese Medicine
- K.C. Wong Education Foundation
- New Star Program, Shanghai Institute of Materia Medica, CAS
Small unilamellar vesicles (SUVs), ubiquitous in organisms, play key and active roles in various biological processes. Although the physical properties of the constituent lipid molecules (i.e., the acyl chain length and saturation) are known to affect the mechanical properties of SUVs and consequently regulate their biological behaviors and functions, the underlying mechanism remains elusive. Here, we combined theoretical modeling and experimental investigation to probe the mechanical behaviors of SUVs with different lipid compositions. The membrane bending rigidity of SUVs increased with increasing chain length and saturation, resulting in differences in the vesicle rigidity and deformable capacity. Furthermore, we tested the tumor delivery capacity of liposomes with low, intermediate, and high rigidity as typical models for SUVs. Interestingly, liposomes with intermediate rigidity exhibited better tumor extracellular matrix diffusion and multicellular spheroid (MCS) penetration and retention than that of their stiffer or softer counterparts, contributing to improved tumor suppression. Stiff SUVs had superior cellular internalization capacity but intermediate tumor delivery efficacy. Stimulated emission depletion microscopy directly showed that the optimal formulation was able to transform to a rod-like shape in MCSs, which stimulated fast transport in tumor tissues. In contrast, stiff liposomes hardly deformed, whereas soft liposomes changed their shape irregularly, which slowed their MCS penetration. Our findings introduce special perspectives from which to map the detailed mechanical properties of SUVs with different compositions, provide clues for understanding the biological functions of SUVs, and suggest that liposome mechanics may be a design parameter for enhancing drug delivery.
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