Nanoparticle elasticity directs tumor uptake

Peng Guo; Daxing Liu; Kriti Subramanyam; Biran Wang; Jiang Yang; Jing Huang; Debra T Auguste; Marsha A Moses

doi:10.1038/s41467-017-02588-9

Nanoparticle elasticity directs tumor uptake

Nat Commun. 2018 Jan 9;9(1):130. doi: 10.1038/s41467-017-02588-9.

Authors

Peng Guo^{1

2

3}, Daxing Liu^{3

4}, Kriti Subramanyam^{1

5

6}, Biran Wang^{3

7}, Jiang Yang^{1

2}, Jing Huang^{1

2}, Debra T Auguste^{8

9}, Marsha A Moses^{10

11}

Affiliations

¹ Vascular Biology Program, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
² Department of Surgery, Harvard Medical School and Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
³ Department of Biomedical Engineering, The City College of New York, 160 Convent Avenue, New York, NY, 10031, USA.
⁴ Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA, 02115, USA.
⁵ School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, Cambridge, MA, 02115, USA.
⁶ Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA, 02139, USA.
⁷ Department of Industrial & Systems Engineering, Texas A&M University, 101 Bizzell Street, College Station, TX, 77843, USA.
⁸ Department of Biomedical Engineering, The City College of New York, 160 Convent Avenue, New York, NY, 10031, USA. d.auguste@northeastern.edu.
⁹ Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA, 02115, USA. d.auguste@northeastern.edu.
¹⁰ Vascular Biology Program, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA. marsha.moses@childrens.harvard.edu.
¹¹ Department of Surgery, Harvard Medical School and Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA. marsha.moses@childrens.harvard.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology
Cell Line
Cell Line, Tumor
Chlorpromazine / pharmacology
Elastic Modulus*
Endocytosis / drug effects
Filipin / pharmacology
Humans
Hydrazones / pharmacology
Liver / metabolism
MCF-7 Cells
Mammary Neoplasms, Experimental / metabolism
Mice, Inbred BALB C
Microscopy, Atomic Force
Nanoparticles / chemistry*
Nanoparticles / metabolism*

Substances

Hydrazones
N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide
Filipin
Chlorpromazine

Abstract

Publication types

MeSH terms

Substances

Grants and funding