DC3-Decorated Polyplexes for Targeted Gene Delivery into Dendritic Cells

PEG比率 化学 共轭体系 组合化学 聚乙二醇 半胱氨酸 生物化学 有机化学 聚合物 财务 经济
作者
Adi Golani‐Armon,Moran Golan,Yosi Shamay,Lior Raviv,Ayelet David
出处
期刊:Bioconjugate Chemistry [American Chemical Society]
卷期号:26 (2): 213-224 被引量:13
标识
DOI:10.1021/bc500529d
摘要

Dendritic cells (DCs) are a family of specialized antigen presenting cells (APCs) that detect antigens and initiate a wide spectrum of immune responses against them. These characteristics make them promising candidates for immunotherapy manipulations. In this study we designed and synthesized DC-targeted block copolymers composed of linear polyethylenimine (PEI) conjugated to hydrophilic polyethylene glycol (PEG) installed with a DC-targeting peptide (DC3, primary sequence FYPSYHSTPQRP). Two different conjugation procedures (basic and modified) were employed to synthesize the DC3-PEG-b-PEI and the control SCRM-PEG-b-PEI (with a scrambled DC3 peptide sequence) by one-pot synthesis, in two steps. In the first, basic conjugation procedure, PEG with N-hydroxysuccinimide (NHS) ester and maleimide (MAL) groups (NHS-PEG-MAL, 3.5 kDa) was first coupled to linear PEI (25 kDa) via the NHS group to yield the intermediate MAL-PEG-b-PEI, that was then conjugated to N-terminus-cysteine harboring peptides DC3 or SCRM via the MAL double bond to yield the final DC3-PEG-b-PEI or SCRM-PEG-b-PEI copolymers, respectively. In the second, modified conjugation procedure, Fmoc-cysteine harboring DC3 or SCRM peptides were first conjugated to NHS-PEG-MAL via the MAL group followed by coupling to linear PEI via the NHS functional group. Fmoc cleavage yielded the same final product as in the basic procedure. The modified conjugation procedure was capable of yielding block copolymers richer with peptides, as determined by (1)H NMR analysis. Self-assembly of DC3-PEG-b-PEI copolymers and DNA molecules yielded nanosized polyion complexes (polyplexes), with lower surface charge and limited cytotoxicity when compared to the PEI building block. Significant transfection efficiency of the DC-targeted polyplexes by murine dendritic DC2.4 cells was observed only in DC3-PEG-b-PEI/DNA polyplexes synthesized by the modified conjugation procedure. These polyplexes, with higher peptide-load, showed greater transfection capability in DC2.4 cells relative to the control nontargeted SCRM-PEG-b-PEI/DNA polyplexes, but not in endothelial cells. The transfection efficiency was comparable to or higher than that of the PEI/DNA positive control. The results indicate that PEGylated-PEI polyplexes show significant transfection efficiency into DCs when decorated with DC3 peptide, and are attractive candidates for immunotherapy via DCs.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
DNase发布了新的文献求助10
1秒前
搜集达人应助唐唐采纳,获得10
1秒前
elysia发布了新的文献求助10
2秒前
Ava应助JINNA采纳,获得10
2秒前
了阿郎完成签到,获得积分10
2秒前
yy关注了科研通微信公众号
2秒前
李健应助yes采纳,获得10
3秒前
4秒前
4秒前
我是老大应助山丘采纳,获得10
4秒前
QUA应助Aten采纳,获得10
4秒前
5秒前
火星上香菇完成签到,获得积分20
5秒前
5秒前
笨小孩发布了新的文献求助10
6秒前
科目三应助小龚热心肠采纳,获得10
6秒前
活泼的机器猫完成签到,获得积分10
6秒前
7秒前
合适夏天完成签到,获得积分10
7秒前
鸽子的迷信完成签到,获得积分10
7秒前
8秒前
8秒前
jeanshe619完成签到,获得积分20
10秒前
李慧颖完成签到 ,获得积分20
10秒前
10秒前
花粉过敏完成签到,获得积分10
11秒前
11秒前
852应助乌龟娟采纳,获得10
11秒前
田様应助ly采纳,获得10
12秒前
12秒前
ouyggg发布了新的文献求助10
12秒前
杜四十929完成签到,获得积分10
12秒前
阿南完成签到,获得积分10
13秒前
量子星尘发布了新的文献求助10
14秒前
14秒前
JamesPei应助科研渣渣采纳,获得10
15秒前
djiwisksk66发布了新的文献求助10
15秒前
15秒前
背后的穆完成签到,获得积分10
16秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3970572
求助须知:如何正确求助?哪些是违规求助? 3515219
关于积分的说明 11177438
捐赠科研通 3250374
什么是DOI,文献DOI怎么找? 1795265
邀请新用户注册赠送积分活动 875750
科研通“疑难数据库(出版商)”最低求助积分说明 805054