PEGylated Polyamidoamine dendrimer conjugated with tumor homing peptide as a potential targeted delivery system for glioma

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 147; pp. 242 - 249
• Main Authors: Jiang, Yan, Lv, Lingyan, Shi, Huihui, Hua, Yabing, Lv, Wei, Wang, Xiuzhen, Xin, Hongliang, Xu, Qunwei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2016
• Subjects: Animals; Blood-Brain Barrier - drug effects; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Proliferation - drug effects; Cysteamine - administration & dosage; Cysteamine - analogs & derivatives; Cysteamine - chemistry; Cysteamine - pharmacokinetics; Dendrimers; Dendrimers - administration & dosage; Dendrimers - chemistry; Drug Delivery Systems; Endocytosis; Fluorescence; Glioblastoma; Glioma - drug therapy; Glioma - metabolism; Glioma - pathology; Humans; Interleukin 13 receptor α2; Interleukin-13 Receptor alpha2 Subunit - administration & dosage; Interleukin-13 Receptor alpha2 Subunit - chemistry; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Nanostructure; Penetration; Pep-1 peptide; Peptides; Peptides - administration & dosage; Peptides - chemistry; Peptides - pharmacokinetics; Polyamidoamine dendrimer; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - chemistry; Targeted nanocarrier; Tissue Distribution; Tumor Cells, Cultured; Tumors; Pep-1 peptide; Interleukin 13 receptor α2; Targeted nanocarrier; Glioblastoma; Polyamidoamine dendrimer
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2016.08.002

[Display omitted] •PEGylated PAMAM was utilized its small size and perfect penetration into tumor.•Pep-1 was used to overcome BBTB via interleukin IL-13Rα2 mediated endocytosis.•Pep-PEG-PAMAM was a promising nanocarrier for targeted delivery of brain glioma. Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system (CNS) tumor with a short survival time. The failure of chemotherapy is ascribed to the low transport of chemotherapeutics across the Blood Brain Tumor Barrier (BBTB) and poor penetration into tumor tissue. In order to overcome the two barriers, small nanoparticles with active targeted capability are urgently needed for GBM drug delivery. In this study, we proposed PEGylated Polyamidoamine (PAMAM) dendrimer nanoparticles conjugated with glioma homing peptides (Pep-1) as potential glioma targeting delivery system (Pep-PEG-PAMAM), where PEGylated PAMAM dendrimer nanoparticle was utilized as carrier due to its small size and perfect penetration into tumor and Pep-1 was used to overcome BBTB via interleukin 13 receptor α2 (IL-13Rα2) mediated endocytosis. The preliminary availability and safety of Pep-PEG-PAMAM as a nanocarrier for glioma was evaluated. In vitro results indicated that a significantly higher amount of Pep-PEG-PAMAM was endocytosed by U87 MG cells. In vivo fluorescence imaging of U87MG tumor-bearing mice confirmed that the fluorescence intensity at glioma site of targeted group was 2.02 folds higher than that of untargeted group (**p<0.01), and glioma distribution experiment further revealed that Pep-PEG-PAMAM exhibited a significantly enhanced accumulation and improved penetration at tumor site. In conclusion, Pep-1 modified PAMAM was a promising nanocarrier for targeted delivery of brain glioma.