Improved anti-glioblastoma efficacy by IL-13Rα2 mediated copolymer nanoparticles loaded with paclitaxel

Abstract

Glioma presents one of the most malignant brain tumors, and the therapeutic effect is often limited due to the existence of brain tumor barrier. Based on interleukin-13 receptor α2 (IL-13Rα2) over-expression on glioma cell, it was demonstrated to be a potential receptor for glioma targeting. In this study, Pep-1-conjugated PEGylated nanoparticles loaded with paclitaxel (Pep-NP-PTX) were developed as a targeting drug delivery system for glioma treatment. The Pep-NP-PTX presented satisfactory size of 95.78 nm with narrow size distribution. Compared with NP-PTX, Pep-NP-PTX exhibited significantly enhanced cellular uptake in C6 cells (p < 0.001). The in vitro anti-proliferation evaluation showed that the IC50 were 146 ng/ml and 349 ng/ml of Pep-NP-PTX and NP-PTX, respectively. The in vivo fluorescent image results indicated that Pep-NP had higher specificity and efficiency in intracranial tumor accumulation. Following intravenous administration, Pep-NP-PTX could enhance the distribution of PTX in vivo glioma section, 1.98, 1.91 and 1.53-fold over that of NP-PTX group after 0.5, 1 and 4 h, respectively. Pep-NP-PTX could improve the anti-glioma efficacy with a median survival time of 32 days, which was significantly longer than that of PTX-NP (23 days) and Taxol® (22 days). In conclusion, Pep-NP-PTX is a potential targeting drug delivery system for glioma treatment.

Magnetic targeting of paclitaxel-loaded poly(lactic-<em>co</em>-glycolic acid)-based nanoparticles for the treatment of glioblastoma

“…Blood samples were collected after 24 h for hematologic and histochemical analysis. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatine kinase isoenzyme (CKMB) levels were assayed 25 using a Fujifilm DRI-CHEM NX500i Analyzer (Fujifilm, Tokyo, Japan).…”

“…Moreover, most of the intravenously injected NPs are taken up and taken up and eliminated by RES organs which includes liver and kidneys. 25 Therefore, AST and ALT for hepatic function, BUN for kidney function and CKMB as cardiac markers were measured on day 1 and day 7 after treatment injection.…”

Targeting experimental orthotopic glioblastoma with chitosan-based superparamagnetic iron oxide nanoparticles (CS-DX-SPIONs)

“…46 Presumably, further modifications of the surface of CS-DX-SPIONs with targeting bioligands (eg, antibodies, peptides, proteins, etc) could further increase the accumulation of particles inside glioma tissue. Previously, several studies demonstrated that coating with tumortargeting molecules including anti-Hsp70 antibody, 16 peptide-targeting interleukin-13 receptor α2 (IL-13Rα2), 47 anti-VEGF antibodies, 48 antibodies toward EGFR deletion mutant (EGFRvIII), 49 anti-insulin-like growth factor binding protein 7 (anti-IGFBP7) single domain antibody, 50 and many others could show an enhanced particle retention inside tumor cells. [51][52][53][54]…”

Development of bioactive materials for glioblastoma therapy

“…The PLGA nanoparticles exhibited long circulation and deeper penetration in glioma spheroids. However, for the in vivo distribution, higher concentration of the injected nanoparticles accumulated in liver and spleen [57] . This greatly reduced the sufficient drug entry into brain tumor.…”

“…It had been applied in many delivery systems against various diseases, including tumors. Also, the PLGA nanoparticles prepared by nano-emulsion could be played as efficient carriers across the blood-brain barrier [45] , [57] , [58] . For example, a cyclic nine amino peptide, CRTIGPSVG (CRT), was introduced into poly(ethylene glycol)-poly( d , l -lactic- co -glycolic acid) (PEG-PLGA) [59] , with a final diameter of 118.8 nm.…”