Octreotide Functionalized Nano-Contrast Agent for Targeted Magnetic Resonance Imaging

被引:20
作者
Jackson, Alexander W. [1 ]
Chandrasekharan, Prashant [2 ]
Ramasamy, Boominathan [2 ]
Goggi, Julian [2 ,3 ]
Chuang, Kai-Hsiang [2 ,3 ,4 ]
He, Tao [1 ]
Robins, Edward G. [2 ,4 ]
机构
[1] ASTAR, Inst Chem & Engn Sci, 1 Pesek Rd, Singapore 627833, Singapore
[2] ASTAR, Singapore Bioimaging Consortium, 11 Biopolis Way, Singapore, Singapore
[3] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117456, Singapore
[4] Natl Univ Singapore, Yong Loo Lin Sch Med, Clin Imaging Res Ctr, Singapore 117599, Singapore
关键词
TRIGGERED DRUG-RELEASE; IN-VITRO; STAR POLYMERS; SOMATOSTATIN RECEPTOR; PARAMAGNETIC LIPOSOMES; RAFT POLYMERIZATION; MRI; NANOPARTICLES; DENDRIMERS; DELIVERY;
D O I
10.1021/acs.biomac.6b01256
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Reversible addition-fragmentation chain transfer (RAFT) polymerization has been employed to synthesize branched block copolymer nanoparticles possessing 1,4,7,10-tetraazacyclo dodecane-N,N',N",N"',-tetraaceticacid (DO3A) macrocycles within their cores and octreotide (somatostatin mimic) cyclic peptides at their periphery. These polymeric nanoparticles have been chelated with Gd3+ and applied as magnetic resonance imaging (MRI) nanocontrast agents. This nanoparticle system has an r(1) relaxivity of 8.3 mM(-1) s(-1), which is 3 times the r1 of commercial gadolinium-based contrast agents (GBCAs). The in vitro targeted binding efficiency of these nanoparticles shows 5 times greater affinity to somatostatin receptor type 2 (SSTR2) with K-i = 77 pM (compared to somatostatin with K-i = 0.385 nM). We have also evaluated the tumor targeting molecular imaging ability of these branched copolymer nanoparticle in vivo using nude/NCr mice bearing AR42J rat pancreatic tumor (SSTR2 positive) and A549 human lung carcinoma tumor (SSTR2 negative) xenografts.
引用
收藏
页码:3902 / 3910
页数:9
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