HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Peptide mediated active targeting and intelligent particle size reduction-mediated enhanced penetrating of fabricated nanoparticles for triple-negative breast cancer treatment.

Abstract
Triple-negative breast cancer (TNBC) is one of the most invasively malignant human cancers and its incidence increases year by year. Effective therapeutics against them needs to be developed urgently. In this study, a kind of angiopep-2 modified and intelligently particle size-reducible NPs, Angio-DOX-DGL-GNP, was designed for accomplishing both high accumulation and deep penetration within tumor tissues. On one hand, for improving the cancerous targeting efficiency of NPs, angiopep-2 was anchored on the surface of NPs to facilitate their accumulation via binding with low density lipoprotein-receptor related protein (LRP) overexpressed on TNBC. On the other hand, for achieving high tumor retention and increasing tumor penetration, an intelligently particle size-reducible NPs were constructed through fabricating gelatin NPs (GNP) with doxorubicin (DOX) loaded dendrigraft poly-lysine (DGL). In vitro cellular uptake and ex-vivo imaging proved the tumor targeting effect of Angio-DOX-DGL-GNP. Additionally, the degradation of large-sized Angio-DOX-DGL-GNP by matrix metalloproteinase-2 (MMP-2) led to the size reduction from 185.7 nm to 55.6 nm. More importantly, the penetration ability of Angio-DOX-DGL-GNP after incubation with MMP-2 was dominantly enhanced in tumor spheroids. Due to a combinational effect of active targeting and deep tumor penetration, the tumor growth inhibition rate of Angio-DOX-DGL-GNP was 74.1% in a 4T1 breast cancer bearing mouse model, which was significantly higher than other groups. Taken together, we successfully demonstrated a promising and effective nanoplatform for TNBC treatment.
AuthorsGuanlian Hu, Xingli Chun, Yang Wang, Qin He, Huile Gao
JournalOncotarget (Oncotarget) Vol. 6 Issue 38 Pg. 41258-74 (Dec 01 2015) ISSN: 1949-2553 [Electronic] United States
PMID26517810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiopep-2
  • Dendrimers
  • Peptides
  • Polylysine
  • Doxorubicin
  • Matrix Metalloproteinase 2
Topics
  • Animals
  • Apoptosis (drug effects)
  • Cell Line, Tumor
  • Cells, Cultured
  • Dendrimers (chemistry)
  • Doxorubicin (chemistry, pharmacokinetics, pharmacology)
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mammary Neoplasms, Experimental (drug therapy, metabolism, pathology)
  • Matrix Metalloproteinase 2 (metabolism)
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • Nanoparticles (administration & dosage, chemistry)
  • Particle Size
  • Peptides (chemistry, pharmacokinetics, pharmacology)
  • Polylysine (chemistry)
  • Spectroscopy, Fourier Transform Infrared
  • Treatment Outcome
  • Triple Negative Breast Neoplasms (drug therapy, metabolism, pathology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: