The Effects of Spacer Length and Composition on Aptamer-Mediated Cell-Specific Targeting with Nanoscale PEGylated Liposomal Doxorubicin.
Aptamer-based targeted drug delivery systems have shown significant promise for clinical applications. Although much progress has been made in this area, it remains unclear how PEG coating would affect the selective binding of DNA aptamers and thus influence the overall targeting efficiency. To answer this question, we herein report a systematic investigation of the interactions between PEG and DNA aptamers on the surface of liposomes by using a series of nanoscale liposomal doxorubicin formulations with different DNA aptamer and PEG modifications. We investigated how the spatial size and composition of the spacer molecules affected the targeting ability of the liposome delivery system. We showed that a spacer of appropriate length was critical to overcome the shielding from surrounding PEG molecules in order to achieve the best targeting effect, regardless of the spacer composition. Our findings provide important guidelines for the design of aptamer-based targeted drug delivery systems.
Department of Chemistry, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N Mathews Avenue, Urbana, IL, 61801, USA.
Hang
0000-0003-3917-8343
H
Xing
Department of Chemistry, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N Mathews Avenue, Urbana, IL, 61801, USA.
Ji
J
Li
Department of Chemistry, Tsinghua University, Beijing, 100084, China.
Weidong
W
Xu
Department of Chemistry, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N Mathews Avenue, Urbana, IL, 61801, USA.
Kevin
K
Hwang
Department of Chemistry, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N Mathews Avenue, Urbana, IL, 61801, USA.
Peiwen
P
Wu
Material Science and Engineering, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N Mathews Avenue, Urbana, IL, 61801, USA.
Qian
Q
Yin
Department of Chemistry, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N Mathews Avenue, Urbana, IL, 61801, USA.
Zhensheng
Z
Li
Material Science and Engineering, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N Mathews Avenue, Urbana, IL, 61801, USA.
Jianjun
J
Cheng
Department of Chemistry, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N Mathews Avenue, Urbana, IL, 61801, USA. yi-lu@illinois.edu.
Yi
Y
Lu
D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001483:Base Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D020285:Cryoelectron Microscopy; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000067493:Dynamic Light Scattering; D006801:Humans; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D052157:Aptamers, Nucleotide; D010713:Phosphatidylcholines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002784:Cholesterol
DNA aptamers; PEG modification; drug delivery; liposomes