Glioblastoma multiforme (GBM) is the most aggressive central nervous system (CNS)
tumor because of its fast development, poor prognosis, difficult control and terrible mortality. Poor penetration and retention in the
glioblastoma parenchyma were crucial challenges in GBM nanomedicine
therapy. Nanoparticle diameter can significantly influence the delivery efficiency in
tumor tissue. Decreasing nanoparticle size can improve the nanoparticle penetration in
tumor tissue but decrease the nanoparticle retention effect. Therefore, small nanoparticles with high retention effect in
tumor are urgently needed for effective GBM
drug delivery. In present study, a small
nanoparticle drug delivery system was developed by conjugating
fibrin-binding
peptide CREKA to
Polyamidoamine (
PAMAM) dendrimer, where PEGylated PAMAM is used as
drug carrier due to its small size and good penetration in
tumor and CREKA is used to target the abundant
fibrin in GBM for enhanced retention in
tumor. In vitro binding ability tests demonstrated that CREKA can significantly enhanced nanoparticle binding with
fibrin. In vivo fluorescence imaging of GBM bearing nude mice, ex vivo brain imaging and frozen slices fluorescence imaging further revealed that the CREKA-modified PAMAM achieved higher accumulation and deeper penetration in GBM tissue than unmodified one. These results indicated that the CREKA-modified PAMAM could penetrate the GBM tissue deeply and enhance the retention effect, which was a promising strategy for
brain tumor therapy.