Micelle-like luminescent nanoparticles as a visible gene delivery system with reduced toxicity.

Cationic polymers have been widely used as promising non-viral gene carriers, but their undesirable toxicity is a drawback. Hydrophobic modification has been developed as an efficient strategy to overcome this disadvantage. In this study, 25 kDa polyethyleneimine (PEI), the gold standard of polycations for effective gene delivery, was modified with the hydrophobic luminogen tetraphenylethene (TPE), which shows aggregation-induced emission (AIE) and has been utilized as a luminescent probe in various applications. The modified PEI (TPEI) self-assembled into micelle-like nanoparticles (TPEI-NPs) and displayed AIE behavior in aqueous media. The TPEI-NPs exhibited bright blue fluorescence and were suitable for long-term cell imaging. Compared with PEI, TPEI-NPs showed lower cytotoxicity but the transfection efficiency was nearly high. Therefore, the modification of polycations with hydrophobic fluorescent molecules represents an advanced strategy for designing visible gene vehicles with low toxicity.

[1]  B. Tang,et al.  AIE macromolecules: syntheses, structures and functionalities. , 2014, Chemical Society reviews.

[2]  M. Eremets,et al.  Ammonia as a case study for the spontaneous ionization of a simple hydrogen-bonded compound , 2014, Nature Communications.

[3]  Xing-jie Liang,et al.  Imaging intracellular anticancer drug delivery by self-assembly micelles with aggregation-induced emission (AIE micelles). , 2014, ACS applied materials & interfaces.

[4]  Xu Zhang,et al.  Salt-responsive self-assembly of luminescent hydrogel with intrinsic gelation-enhanced emission. , 2014, ACS applied materials & interfaces.

[5]  Ryan T. K. Kwok,et al.  Long-term fluorescent cellular tracing by the aggregates of AIE bioconjugates. , 2013, Journal of the American Chemical Society.

[6]  D. Tomalia,et al.  CommentaryDendrimers in biomedical applications—reflections on the field☆☆☆ , 2012 .

[7]  G. Bazan,et al.  A Highly Emissive Conjugated Polyelectrolyte Vector for Gene Delivery and Transfection , 2012, Advanced materials.

[8]  Lorenzo Moroni,et al.  Cationic polymers and their therapeutic potential. , 2012, Chemical Society reviews.

[9]  N. Wiradharma,et al.  Diaminododecane-based cationic bolaamphiphile as a non-viral gene delivery carrier. , 2012, Biomaterials.

[10]  C. Berkland,et al.  Intratracheal administration of a nanoparticle-based therapy with the angiotensin II type 2 receptor gene attenuates lung cancer growth. , 2012, Cancer research.

[11]  Ben Zhong Tang,et al.  Aggregation-induced emission. , 2011, Chemical Society reviews.

[12]  Gang Liu,et al.  FUNCTIONAL NANOPARTICLES FOR MOLECULAR IMAGING GUIDED GENE DELIVERY. , 2010, Nano today.

[13]  Changren Zhou,et al.  Hydrophobic modifications of cationic polymers for gene delivery , 2010 .

[14]  B. Tang,et al.  Aggregation-induced emission: phenomenon, mechanism and applications. , 2009, Chemical Communications.

[15]  A. Mohs,et al.  Bioconjugated quantum dots for in vivo molecular and cellular imaging. , 2008, Advanced drug delivery reviews.

[16]  D. Putnam,et al.  Polymer systems for gene delivery - Past, present, and future , 2007 .

[17]  Sung Wan Kim,et al.  Current status of polymeric gene delivery systems. , 2006, Advanced drug delivery reviews.

[18]  R. Langer,et al.  Designing materials for biology and medicine , 2004, Nature.

[19]  Vincent Noireaux,et al.  In Vivo Imaging of Quantum Dots Encapsulated in Phospholipid Micelles , 2002, Science.

[20]  A. Klibanov,et al.  Enhancing polyethylenimine's delivery of plasmid DNA into mammalian cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[21]  A. Mikos,et al.  Poly(ethylenimine) and its role in gene delivery. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[22]  J. Behr,et al.  Transfection and physical properties of various saccharide, poly(ethylene glycol), and antibody‐derivatized polyethylenimines (PEI) , 1999, The journal of gene medicine.

[23]  Ronald G. Crystal,et al.  Transfer of Genes to Humans: Early Lessons and Obstacles to Success , 1995, Science.

[24]  Paul C. Wang,et al.  Amphiphilic and biodegradable methoxy polyethylene glycol-block-(polycaprolactone-graft-poly(2-(dimethylamino)ethyl methacrylate)) as an effective gene carrier. , 2011, Biomaterials.

[25]  H. Uludaǧ,et al.  Formulation and delivery of siRNA by oleic acid and stearic acid modified polyethylenimine. , 2009, Molecular pharmaceutics.

[26]  Xuesi Chen,et al.  Gene transfection of hyperbranched PEI grafted by hydrophobic amino acid segment PBLG. , 2007, Biomaterials.