Hyaluronic acid modification of RNase A and its intracellular delivery using lipid-like nanoparticles.
Developing safe and effective nanosystems to deliver active and therapeutic proteins to targeted cells and organs is an important tool for many biomedical applications. We present here a simple and efficient strategy for this purpose: delivering hyaluronic acid (HA)-modified RNase A (RNase A-HA) in nanocomplex with cationic lipid-like molecules (lipidoids) to cancer cells, resulting in targeted inhibition of cancer proliferation. The chemical conjugation of RNase A with HA both increased the supramolecular interaction with carrier lipidoids, promoting protein encapsulation efficacy, and facilitated cancer cell targeting via interaction with overexpressed CD44. Through confocal laser scanning microscopy and flow cytometry analysis, we demonstrated that protein/lipidoid nanoparticles could facilely enter cells with high CD44 expression, and inhibit cell proliferation in a dose-dependent manner.
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA; Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
Xiaoying
X
Wang
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Yamin
Y
Li
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA; Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
Quanshun
Q
Li
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Caleb I
CI
Neufeld
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Dimitra
D
Pouli
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Shuo
S
Sun
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Liu
L
Yang
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Pu
P
Deng
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA; Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Ming
M
Wang
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Irene
I
Georgakoudi
Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
Shunqing
S
Tang
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA. Electronic address: Qiaobing.Xu@tufts.edu.
Qiaobing
Q
Xu
D000072283:A549 Cells; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry; D008055:Lipids / Q000008:administration & dosage* / Q000737:chemistry; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D012260:Ribonucleases / Q000008:administration & dosage* / Q000737:chemistry
C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D008055:Lipids; D006820:Hyaluronic Acid; D012260:Ribonucleases
CD44; Hyaluronic acid; Lipidoids; Protein engineering; Targeted protein delivery