PMID- 30145338 OWN - NLM STAT- MEDLINE DCOM- 20190109 LR - 20190109 IS - 1879-0720 (Electronic) IS - 0928-0987 (Linking) VI - 124 DP - 2018 Nov 1 TI - Polymeric nanoparticles decorated with BDNF-derived peptide for neuron-targeted delivery of PTEN inhibitor. PG - 37-45 LID - S0928-0987(18)30386-5 [pii] LID - 10.1016/j.ejps.2018.08.020 [doi] AB - Biodegradable nanoparticles (PEG-PCL) decorated with tetra peptides (IKRG) on the surface were evaluated for their potential to deliver drugs into neurons for neural regeneration. The chosen 4-amino-acid peptide sequence was reported previously to mimic the function of BDNF (brain-derived neurotrophic factor) and target TrkB receptors that are present in abundance in neurons. Enhanced uptake for peptide-modified nanoparticles was observed in TrkB-positive PC12 cells but not in TrkB-negative HeLa cells. The modified nanoparticles were internalized selectively into neurons of dorsal root ganglion (DRG) and at a significantly higher rate. VO-OHpic, an inhibitor of PTEN (Phosphatase and tension homolog deleted on chromosome 10), was encapsulated into the modified nanoparticles and released over 14 days. Prolonged and enhanced neural regenerative effect, as confirmed by increased pAKT expression and increased neurite density, was observed when DRGs were treated with drug-containing nanoparticles. This was attributed to the increased and targeted cellular uptake and sustainable release by the peptide-modified nanoparticles. Furthermore, nanoparticle encapsulation was found to reduce the cytotoxicity of the free drug to the neurons. Our findings support that the BDNF-derived peptide modified PEG-PCL nanoparticles are promising carriers for localized and controlled drug delivery to peripheral neurons. CI - Copyright (c) 2018. Published by Elsevier B.V. FAU - Xu, Jing AU - Xu J AD - Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. FAU - Chau, Ying AU - Chau Y AD - Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address: keychau@ust.hk. LA - eng PT - Journal Article DEP - 20180823 PL - Netherlands TA - Eur J Pharm Sci JT - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JID - 9317982 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Peptides) RN - 0 (Polyesters) RN - 24980-41-4 (polycaprolactone) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) SB - IM MH - Animals MH - *Brain-Derived Neurotrophic Factor MH - *Drug Delivery Systems MH - Ganglia, Spinal/metabolism MH - HeLa Cells MH - Humans MH - Mice, Inbred C57BL MH - Nanoparticles/*administration & dosage MH - Neurons/metabolism MH - PC12 Cells MH - PTEN Phosphohydrolase/*antagonists & inhibitors/metabolism MH - Peptides/*administration & dosage MH - Polyesters/*administration & dosage MH - Polyethylene Glycols/*administration & dosage MH - Rats OTO - NOTNLM OT - Dorsal root ganglion OT - Drug delivery OT - Neuron regeneration OT - Neuron targeting OT - PTEN inhibition OT - Polymeric nanoparticles EDAT- 2018/08/27 06:00 MHDA- 2019/01/10 06:00 CRDT- 2018/08/27 06:00 PHST- 2018/05/26 00:00 [received] PHST- 2018/08/05 00:00 [revised] PHST- 2018/08/16 00:00 [accepted] PHST- 2018/08/27 06:00 [pubmed] PHST- 2019/01/10 06:00 [medline] PHST- 2018/08/27 06:00 [entrez] AID - S0928-0987(18)30386-5 [pii] AID - 10.1016/j.ejps.2018.08.020 [doi] PST - ppublish SO - Eur J Pharm Sci. 2018 Nov 1;124:37-45. doi: 10.1016/j.ejps.2018.08.020. Epub 2018 Aug 23.