A supramolecular approach for preparation of size-controlled nanoparticles.

A supramolecular approach for preparation of size-controlled nanoparticles.
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DOI:
10.1002/anie.200900063
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发表时间:
2009
影响因子:
16.6
通讯作者:
Tseng, Hsian-Rong
Tseng, Hsian-Rong
中科院分区:
化学1区
文献类型:
--
作者:
Wang, Hao;Wang, Shutao;Su, Helen;Chen, Kuan-Ju;Armijo, Amanda Lee;Lin, Wei-Yu;Wang, Yanju;Sun, Jing;Kamei, Ken-ichiro;Czernin, Johannes;Radu, Caius G.;Tseng, Hsian-Rong

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Over the past decades, significant efforts have been devoted to explore the use of nanoparticles in the fields of biology and medicine. Several different types of nanoparticles have successfully made their way into preclinical studies in animals, clinic trials in patients, or even successful commercial products used in routine clinical practice.[1] For example, gold nanoshells,[2] quantum dots,[3, 4] and super-paramagnetic nanoparticles [5] that carry target-specific ligands have been employed for in vivo imaging of cancerous cells; drug molecules have been packaged into polymer-based nanoparticles and/or liposomes [6, 7] to achieve controlled release at the disease sites;[8, 9] and positively charged nanoparticles have served as nonviral delivery systems for both in vitro and in vivo genetic manipulation and programming.[1, 10, 11] However, there remains an imperious desire to develop novel synthetic approaches to produce a new generation of nanoparticles that have 1) controllable sizes and morphologies, 2) low toxicity, compatible immunogenicity and in vivo degradability, and 3) proper surface charges and chemistry for improved physiological stability and longer circulation time. Moreover, multiple functions,[12] such as reporter systems for real-time monitoring with imaging techniques (ie, optical imaging, magnetic resonance imaging (MRI), and positron emission tomography (PET)), targeting ligands for disease-specific delivery, and a controllable mechanism for packaging and releasing drugs and genes, will be conferred to individual nanoparticles for conducting multiple applications in parallel. Unlike conventional chemical synthesis, which is capable of forming/breaking covalent bonds, supramolecular chemistry combines two basic concepts: self assembly and molecular recognition. Supramolecular chemistry offers a powerful and convenient approach for the preparation of nanostructured materials from molecular building blocks.[13–18] The concept of self-assembly has been extensively used to prepare organic nanoparticles. For example, liposomes and nanoscaled vesicles [7] which were prepared using self-assembly of phospholipids can serve as powerful nanocarriers for drug and gene delivery; self-assembled amphiphilic copolymer building blocks spontaneously form nanoparticles, which can be utilized for drug delivery and molecular imaging.[19–22] However, it is apparent that the concept of “molecular recognition” seems to be an underappreciated factor, which could lead to much more sophisticated synthetic approaches,[23] allowing precise control over the properties of the resulting nanoparticles. β-Cyclodextrin (CD) is one of the most commonly used supramolecular building blocks for a diverse range of biomedical applications.[24, 25] CD-containing cationic polymers have been employed as vectors for highly efficient delivery of siRNA. Through CD/adamantane (Ad) recognition, Ad-functionalized polyethylene glycol (PEG) chains were grafted onto the nanoparticles to enable long-term systemic circulation in vivo.[26] Herein, we report a convenient, flexible, and modular synthetic approach (Figure1) for the preparation of sizecontrollable supramolecular nanoparticles (SNPs). CD/Ad recognition was employed to achieve self-assembly of SNPs from three different molecular building blocks, namely 1) Adgrafted first-generation polyamidoamine dendrimer, n-Ad-PAMAM, 2) β-CD-grafted branched polyethylenimine (MW= 10kD), CD-PEI, and 3) Ad-functionalized PEG compound (MW= 5kD), Ad-PEG. Although similar to a previously reported “bricks and mortar” strategy [23] to construct cross-linked network,[27] the uniqueness of our design …
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发表时间: 2008-12
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