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Liposome-Encapsulated Zoledronate Favors Tumor Vascular Normalization and Enhances Anticancer Efficacy of Cisplatin.
- Source :
-
AAPS PharmSciTech [AAPS PharmSciTech] 2020 Jan 07; Vol. 21 (2), pp. 57. Date of Electronic Publication: 2020 Jan 07. - Publication Year :
- 2020
-
Abstract
- The aim of this study was to examine the effectiveness of alanine-proline-arginine-proline-glycine (APRPG) peptide-conjugated PEGylated cationic liposomes-encapsulated zoledronic acid (ZOL) (APRPG-PEG-ZOL-CLPs) in achieving vascular normalization. Cisplatin (diamminedichloroplatinum, DDP) was used to improve anticancer efficacy. The present study showed that APRPG-PEG-ZOL-CLPs increased anticancer efficacy, which was regarded as vascular normalization. Our results demonstrated that the viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were evidently repressed by APRPG-PEG-ZOL-CLPs. Moreover, APRPG-PEG-ZOL-CLPs could decrease vessel density, as well as hypoxia-inducible factor 1α (HIF-1α), and increase thrombospondin 1 (TSP-1) expression of tumors. Therefore, the anticancer efficacy of APRPG-PEG-ZOL-CLPs combined with DDP was superior to that of PEG-ZOL-CLP or ZOL treatment combined with DDP schemes, as demonstrated by the obviously evident reduction in tumor volume. These results indicated that APRPG-PEG-ZOL-CLPs were most effective in normalizing tumor vasculature to elevate the therapeutic effect of antitumor drugs.
- Subjects :
- Animals
Cells, Cultured
Endothelial Cells drug effects
Female
Humans
Liposomes
Mice
Mice, Inbred BALB C
Oligopeptides chemistry
Polyethylene Glycols chemistry
Antineoplastic Agents pharmacology
Cisplatin pharmacology
Neoplasms, Experimental blood supply
Zoledronic Acid administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1530-9932
- Volume :
- 21
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- AAPS PharmSciTech
- Publication Type :
- Academic Journal
- Accession number :
- 31912318
- Full Text :
- https://doi.org/10.1208/s12249-019-1614-6