Poly(ethylene glycol) with observable shedding.

A novel FRET-bearing poly(ethylene glycol) (PEG) conjugate fluoresces at 520 nm when it is cleaved off from nanoparticles (NPs). When the NPs were targeted to cancer cell lines, the reducing redox of the endosomal compartment caused disulfide bond cleavage and shedding of the PEG layer. The fluorescence emission can be suppressed by N-ethylmaleimide to inhibit disulfide cleavage and restored by dithiothreitol, a disulfide cleavage reagent, indicating a direct correlation between fluorescence emission and PEG shedding.

[1]  L. Zhang,et al.  Nanoparticles in Medicine: Therapeutic Applications and Developments , 2008, Clinical pharmacology and therapeutics.

[2]  Yuichi Yamasaki,et al.  PEG-detachable polyplex micelles based on disulfide-linked block catiomers as bioresponsive nonviral gene vectors. , 2008, Journal of the American Chemical Society.

[3]  Robert Langer,et al.  Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers , 2008, Proceedings of the National Academy of Sciences.

[4]  Gert Storm,et al.  Sheddable Coatings for Long-Circulating Nanoparticles , 2007, Pharmaceutical Research.

[5]  Jeffrey A Hubbell,et al.  PEG-SS-PPS: reduction-sensitive disulfide block copolymer vesicles for intracellular drug delivery. , 2007, Biomacromolecules.

[6]  Robert Langer,et al.  Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery. , 2007, Biomaterials.

[7]  Jong-sang Park,et al.  Visualization of the degradation of a disulfide polymer, linear poly(ethylenimine sulfide), for gene delivery. , 2007, Bioconjugate chemistry.

[8]  Philip S Low,et al.  Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging , 2006, Proceedings of the National Academy of Sciences.

[9]  J. Richie,et al.  Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Nicholas A Peppas,et al.  Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. , 2006, International journal of pharmaceutics.

[11]  F. Chang,et al.  Direct comparison of liposomal doxorubicin with or without polyethylene glycol coating in C-26 tumor-bearing mice: is surface coating with polyethylene glycol beneficial? , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[12]  R. Langer,et al.  Drug delivery and targeting. , 1998, Nature.

[13]  M. Bally,et al.  Accumulation of liposomal lipid and encapsulated doxorubicin in murine Lewis lung carcinoma: the lack of beneficial effects by coating liposomes with poly(ethylene glycol). , 1997, The Journal of pharmacology and experimental therapeutics.