Shrapnel nanoparticles loading docetaxel inhibit metastasis and growth of breast cancer.

Abstract

Metastasis is one of the major obstacles for the successful therapy of breast cancer. To inhibit the metastasis and growth of breast cancer simultaneously, a new docetaxel (DTX) loaded shrapnel nano delivery system with the reduction- and enzyme-sensitive properties was designed and developed. Firstly, methoxy polyethylene glycol-peptide-vitamin E succinate (PPV), a matrix metalloproteinases (MMPs)-sensitive copolymer, was synthesized by conjugating mPEG and vitamin E succinate (VES) using an enzyme-sensitive peptide. Then, DTX loaded methoxy polyethylene glycol-s-s-vitamin E succinate (PSV) micelles (DPM) @ PPV-based liposomes (DPM@PL) were prepared by the incorporation of DPM into the PPV-based liposomes. DPM@PL showed a shrapnel structure with average particle size 113.3 ± 2.7 nm. The drug loading and encapsulation efficiency of DPM@PL were 1.93% and 99.02%, respectively. An obvious burst release (>90%) of drug was observed in the simulated tumor microenvironment with MMPs and reductive glutathione. The cellular uptake and cytotoxicity of DPM@PL in 4T1 cells were significantly enhanced after the pre-treatment of activated MMP-9. Compared with Taxotere(®), DPM@PL remarkably increased the distribution of DTX in lung and tumor of 4T1 tumor-bearing mice, and inhibited the in situ tumor growth and pulmonary metastasis formation effectively through the enhanced DTX-induced apoptosis and the reduced metastasis-promoting proteins expression. Compared with saline group, the inhibitory rates of DPM@PL against tumor volume and lung metastasis were about 81% and 92%, respectively, and it didn't produce the significant systemic toxicity. As a result, DPM@PL could be a promising nano delivery system for the successful therapy of breast cancer.

• Authors: Pengfei Xu, Qingshuo Meng, Huiping Sun, Qi Yin, Haijun Yu, Zhiwen Zhang, Mi Cao, Yingyi Zhang, Yaping Li
• Journal: Biomaterials (Biomaterials) Vol. 64 Pg. 10-20 (Sep 2015) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 26106797 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Drug Carriers
• Liposomes
• Micelles
• Neoplasm Proteins
• Phosphatidylcholines
• Taxoids
• Docetaxel
• Polyethylene Glycols
• Tocopherols

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacokinetics, therapeutic use, toxicity)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Docetaxel
• Drug Carriers (administration & dosage)
• Drug Compounding
• Drug Screening Assays, Antitumor
• Female
• Liposomes (administration & dosage)
• Lung Neoplasms (prevention & control, secondary)
• Male
• Mammary Neoplasms, Experimental (drug therapy, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Micelles
• Molecular Structure
• Nanoparticles (administration & dosage, therapeutic use, toxicity)
• Neoplasm Proteins (biosynthesis)
• Particle Size
• Phosphatidylcholines
• Polyethylene Glycols (administration & dosage, chemical synthesis)
• Random Allocation
• Rats, Sprague-Dawley
• Taxoids (administration & dosage, pharmacokinetics, therapeutic use, toxicity)
• Tissue Distribution
• Tocopherols (administration & dosage, chemical synthesis)
• Tumor Microenvironment