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BackgroundFrequent injection of high-dose methylprednisolone (MP) is used to treat spinal cord injury (SCI), but free MP is associated with various side effects and its water solubility is low, limiting potential dosing regimes and administration routes. Albumin-based nanoparticles, which can encapsulate therapeutic drugs and release cargo in a controlled pattern, show high biocompatibility and low toxicity. The Nogo protein, expressed on the surface of oligodendrocytes, can inhibit axonal growth by binding with the axonal Nogo receptor (NgR). Peptide NEP1-40, an NgR antagonist, can bind specifically to Nogo, significantly improving functional recovery and axon growth in the corticospinal tract. Therefore, we hypothesized that delivering MP within nanoparticles decorated with NEP1-40 could avoid the disadvantages of free MP and enhance its therapeutic efficacy against SCI.ResultsWe used human serum albumin to prepare MP-loaded NPs (MP-NPs), to whose surface we conjugated NEP1-40 to form NEP1-40-MP-NPs. Transmission electron microscopy indicated successful formation of nanoparticles. NEP1-40-MP-NPs were taken up significantly better than MP-NPs by the Nogo-positive cell line RSC-96 and were associated with significantly higher Basso–Beattie–Bresnahan locomotor scores in rats recovering from SCI. Micro-computed tomography assay showed that NEP1-40-MP-NPs mitigated SCI-associated loss of bone mineral density and accelerated spinal cord repair.ConclusionsNEP1-40-MP-NPs can enhance the therapeutic effects of MP against SCI. This novel platform may also be useful for delivering other types of drugs. Electronic supplementary materialThe online version of this article (10.1186/s12951-019-0449-3) contains supplementary material, which is available to authorized users.

Liver cancer is a fatal disease with limited therapy options. The recombinant adenovirus expressing tumor-suppressor gene of PTEN (Ad5-PTEN) showed effective antitumor activity against liver cancer. However, its disadvantages produced great limitation on its application, especially its nonspecific and toxicity to normal cells and tissues. The epithelial cell adhesion molecule (EpCAM) is over-expressed in some liver cancer cells and an RNA aptamer EpDT3 could specially target to EpCAM-positive cells. Based on this founding, we aimed to design a kind of gene delivery system of EpDT3-mediated Ad5-PTEN (EpDT3-PEG-Ad5-PTEN, EPAP) in which polyethylene glycol was used to be a linker to conjugate EpDT3 with Ad5-PTEN. This strategy may overcome the disadvantages of naked Ad5-PTEN and enhance the antitumor effect on liver cancer. The SDS-PAGE electrophoresis, TBE-PAGE electrophoresis and fluorescence detection were conducted to confirm the successful preparation of EPAP. Compared with the naked Ad5-PTEN, EPAP showed significant anti-proliferative and anti-migratory activities against HepG2 cells. EPAP also showed selective and precise target ability to EpCAM-positive HepG2 cells in vivo. Therefore, EPAP may be further explored as a novel effective anticancer drug for malignant liver cancer.