The self-assembly of biodegradable cationic polymer micelles as vectors for gene transfection

Wang, Yong; Ke, Chyan Ying; Beh, Cyrus W.; Liu, Shaoqiong; Goh, S. H.; Yang, Yi-Yan

doi:10.1016/j.biomaterials.2007.08.013

Cited by 63 publications

(53 citation statements)

References 19 publications

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“…Meanwhile, diblock copolymer PEG-PLL was obtained after the deprotection of the PEG-PLLZ using the same method. By varying the feed molar ratio of LLZ-NCA and LLeu-NCA to mPEG-NH 2 , six copolymers with different molecular weight, including PEG-PLL 15 The structure of the polymers was characterized using 1 H NMR and FT-IR spectroscopy. The 1 H NMR spectra of PEG-PLLZ-PLLeu and PEG-PLL-PLLeu in CF 3 COOD are shown in Figure 1A,B, respectively.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Self-Assembled Cationic Micelles Based on PEG-PLL-PLLeu Hybrid Polypeptides as Highly Effective Gene Vectors

et al. 2012

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Developing safe and effective nonviral gene vector is highly crucial for successful gene therapy. In the present study, we designed a series of biodegradable micelles based on hybrid polypeptide copolymers of poly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-leucine) (PEG-PLL-PLLeu) for efficient gene delivery. A group of amphiphilic PEG-PLL-PLLeu hybrid polypeptide copolymers were synthesized by ring-opening polymerization of N-carboxyanhydride, and the chemical structure of each copolymer was characterized by (1)H NMR and FT-IR spectroscopy measurement. The PEG-PLL-PLLeu micelles were positively charged with tunable sizes ranging from 40 to 90 nm depending on the length of PLL and PLLeu segment. Compared with PEG-PLL copolymers, PEG-PLL-PLLeu micelles demonstrated significantly higher transfection efficiency and less cytotoxicity. Furthermore, the transfection efficiency and biocompatibility of the micelles can be simultaneously improved by tuning the length of PLL and PLLeu segments. The transfection efficiency of PEG-PLL-PLLeu micelles in vivo was two to three times higher than that of PEI(25k), which was attributable to their capability of promoting DNA condensation and cell internalization as well as successful lysosome escape. Hence well-defined PEG-PLL-PLLeu micelles would serve as highly effective nonviral vectors for in vivo gene delivery.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Self-Assembled Cationic Micelles Based on PEG-PLL-PLLeu Hybrid Polypeptides as Highly Effective Gene Vectors

et al. 2012

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“…For feed PLA molar fractions of 0.06, 0.13, and 0.21, the fraction of PLA incorporated in the terpolymer was 0.037, 0.056, and 0.068, respectively, which demonstrated that the reactivity of PLA with fumaryl chloride was significantly less than that of PEG (69). GPC can be used to determine the optimum polymer or conjugated peptide-polymer conjugate chain length for selfassembly (70). The sequence distribution of the polymerpeptide conjugate can be determined by matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (71).…”

Section: Characterization Of Peptidomimetic Npsmentioning

confidence: 97%

Targeted Delivery with Peptidomimetic Conjugated Self-Assembled Nanoparticles

Jabbari

2008

Pharm Res

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Peptides produce specific nanostructures, making them useful for targeting in biological systems but they have low bioavailability, potential immunogenicity and poor metabolic stability. Peptidomimetic self-assembled NPs can possess biological recognition motifs as well as providing desired engineering properties. Inorganic NPs, coated with self-assembled macromers for stability and anti-fouling, and conjugated with target-specific ligands, are advancing imaging from the anatomy-based level to the molecular level. Ligand conjugated NPs are attractive for cell-selective tumor drug delivery, since this process has high transport capacity as well as ligand dependent cell specificity. Peptidomimetic NPs can provide stronger interaction with surface receptors on tumor cells, resulting in higher uptake and reduced drug resistance. Self-assembled NPs conjugated with peptidomimetic antigens are ideal for sustained presentation of vaccine antigens to dendritic cells and subsequent activation of T cell mediated adaptive immune response. Self-assembled NPs are a viable alternative to encapsulation for sustained delivery of proteins in tissue engineering. Cell penetrating peptides conjugated to NPs are used as intracellular delivery vectors for gene expression and as transfection agents for plasmid delivery. In this work, synthesis, characterization, properties, immunogenicity, and medical applications of peptidomimetic NPs in imaging, tumor delivery, vaccination, tissue engineering, and intracellular delivery are reviewed.

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“…The (co)polymer conjugates self-assemble into cationic micelles in aqueous solution at low pH and are used for gene and drug delivery. Enhanced efficiency of gene transfection and intracellular protein delivery has been observed and ascribed to a more stable core-shell structure of the micelles and to an improved cellular uptake through a cellular Chol uptake pathway [159][160][161].…”

Section: Grafting Of Terpenes Onto Polymer Chainsmentioning

confidence: 97%

“…The degree of quaternization can be roughly controlled by the feed ratio of Chol-Br and backbone units; however, no higher than 60% can be achieved, even with 1.5 equiv. of Chol-Br [159] and is even lower when the backbone polymer is linked with a PEG block [160]. The (co)polymer conjugates self-assemble into cationic micelles in aqueous solution at low pH and are used for gene and drug delivery.…”

Section: Grafting Of Terpenes Onto Polymer Chainsmentioning

confidence: 99%

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Synthesis of Terpene-Based Polymers

Zhao¹,

Schlaad²

2012

Advances in Polymer Science

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Terpenes or terpenoids are a large class of diverse biological compounds derived from isoprene. Due to their abundance in nature and desirable properties, there has been great interest in producing polymers with terpenes as either functional entities or as the main constituent. Terpene-based polymers have found applications as biomedical or liquid crystalline materials and, more importantly, have greatly contributed to the concept of sustainable polymer chemistry. The design and preparation of terpene-based polymers have involved different chemical strategies and a wide variety of polymerization techniques, making use of the chemical functionalities in terpene molecules, e.g. (conjugated) double bonds, hydroxyl and carboxyl groups. This review describes the synthetic methodologies for terpene-based polymers, classified by the position of terpene entities in the polymer chains, i.e., main chain, terminal or central group, and pendant group.

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The self-assembly of biodegradable cationic polymer micelles as vectors for gene transfection

Cited by 63 publications

References 19 publications

Self-Assembled Cationic Micelles Based on PEG-PLL-PLLeu Hybrid Polypeptides as Highly Effective Gene Vectors

Self-Assembled Cationic Micelles Based on PEG-PLL-PLLeu Hybrid Polypeptides as Highly Effective Gene Vectors

Targeted Delivery with Peptidomimetic Conjugated Self-Assembled Nanoparticles

Synthesis of Terpene-Based Polymers

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