Application of dual targeting drug delivery system for the improvement of anti-glioma efficacy of doxorubicin

Abstract

Chemotherapy of glioma is always hampered by the unsatisfactory tumor accumulation of drugs, of which the most noticeable obstacle is the limited drug permeability from vessels into tumor inner. In the present study, we developed a novel nanocarrier for the delivery of doxorubicin to brain tumor. Such novel drug delivery system was mainly composed of a tumor homing peptide and DOX-loaded PLA nanoparticles (AP1-NP-DOX). CRKRLDRNC peptide, named as AP1, was a newly glioma affinity peptide which could specifically binds to interleukin-4 receptor (IL-4R), highly expressing on both glioma cells and angiogenesis. Our findings showed that the peptide-functionalized nanoparticles had a high affinity with both tumor cells and vascular endothelial cells. Besides, tumor targeting assay exhibited that AP1 decorated nanoparticles accumulated more in tumor site than the unmodified ones. Moreover, the results of tumor uptake experiments indicated that AP1-NP-DOX might own the ability of blood brain barrier (BBB) penetration. In the anti-glioma study, AP1-NP-DOX exhibited the highest therapeutic effect on tumor-bearing mice compared with the unmodified nanoparticles and free doxorubicin. These results together indicated that AP1-functionalized nanoparticles could represent a promising way to expand the treatment horizons of onco-therapy.

Antiangiogenic Targets for Glioblastoma Therapy from a Pre-Clinical Approach, Using Nanoformulations

“…Of the 24 articles identified in the Cochrane Library, no articles were included, as 16 articles were reviews, 5 were protocols, and 3 were clinical articles in the screening analysis. In total, only 27 full-text articles not duplicated were included in this systematic review [ 32 , 34 , 38 , 41 , 43 , 44 , 45 , 48 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ], as illustrated in Figure 1 .…”

“…The major tumoral cell characteristics used in the selected studies in our review are shown in Table 1 . Of 27 selected studies for this review, 19 studies (70%) [ 32 , 34 , 38 , 43 , 45 , 48 , 52 , 53 , 55 , 56 , 57 , 58 , 59 , 62 , 63 , 64 , 65 , 66 , 67 ] used tumor cells from a human source, 6 (22%) [ 41 , 51 , 54 , 60 , 61 , 68 ] used tumor cell from rats, and 3 studies (11%) [ 44 , 50 , 66 ] used cells from mice. The study by Agemy [ 66 ] used human and mice tumor cell sources and also used lentivirus H-RasV12-shp53 to induce glioma cells.…”

“…Regarding cell lineage of tumor cells from a human source, most studies (79%) [ 32 , 34 , 38 , 52 , 53 , 55 , 56 , 57 , 58 , 59 , 62 , 63 , 64 , 66 , 67 ] used the U87-MG cell lineage. For tumor cells from a rat source the C6 lineage was used in almost all studies (83%) [ 41 , 51 , 54 , 60 , 61 ], with the exception of Hekmatara [ 68 ], who used 101/8 cells produced initially by the injection of α-dimethylbenzanthracene into the brain Wistar rats; the GL261 lineage was used in two [ 44 , 50 ] of three studies where the tumor cells were from a mice source.…”

“…The induction characteristics of the glioma model using the cells described above, as well as the animals, are described in Table 2 . In all studies in this review, the tumor model was induced in rodents; mice were used in 21 studies (78%) [ 32 , 34 , 41 , 43 , 44 , 45 , 48 , 50 , 51 , 52 , 53 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 66 , 67 ] and rats were used in 6 studies (22%) [ 38 , 54 , 60 , 61 , 65 , 68 ].…”

“…In the review of studies that used mice as a model, the most used species was BALB/C nude [ 41 , 45 , 53 , 56 , 57 , 58 , 59 , 62 ] followed of Nude athymic [ 32 , 51 , 55 , 63 , 67 ] in eight (38%) and five (24%) studies, respectively; C57BL/6 in two studies (10%) [ 44 , 50 ] and the other six studies used different species of mice such as Mut6/cKO [ 64 ], Nonobese diabetic/severe combined immunodeficiency (NOD-SCID) [ 66 ], Swiss nude [ 34 ], CB17-SCID [ 52 ], ICR-Prkdc-SCID [ 48 ], and Rag2M [ 43 ], representing 5% each. Mice used in the selected studies were male (43%) [ 41 , 44 , 45 , 48 , 58 , 59 , 62 , 63 , 64 ] or female (33%) [ 34 , 43 , 50 , 52 , 53 , 57 , 64 ], and the mice age ranged from 4 to 10 weeks in 12 studies (57%) [ 32 , 34 , 41 , 43 , 44 , 50 , 52 , 55 , 56 , 57 , 59 , …”