Tumor-Targeting Micelles Based on Linear-Dendritic PEG-PTX8 Conjugate for Triple Negative Breast Cancer Therapy.

Abstract

Most small molecular chemotherapeutics have poor water solubility and unexpected pharmacokinetics and toxicity to normal tissues. A series of nano drug delivery systems have been developed to solve the problems, among which a micelle based on linear-dendritic polymer-drug conjugates (LDPDCs) is a promising strategy to deliver hydrophobic chemotherapeutics due to its small size, fine stability in blood circulation, and high drug loading capacity. In this work we synthesized a novel amphiphilic linear-dendritic PEG-PTX8 conjugate which can also encapsulate extra free PTX and self-assemble into uniform ultrasmall micelles with a hydrated diameter of 25.50 ± 0.27 nm. To realize efficient drug delivery to tumor sites, a cyclic tumor homing and penetrating peptide iNGR was linked to the PEG-PTX8 conjugate. The biological evaluation was performed on a human triple negative breast cancer model. PTX accumulation in tumor at 24 h of the TNBC-bearing mice treated with iNGR-PEG-PTX8/PTX micelles was significantly enhanced (P < 0.001, two-way ANOVA) compared to that of Taxol and untargeted MeO-PEG-PTX8/PTX micelles. Furthermore, iNGR-PEG-PTX8/PTX micelles showed an obvious strong antitumor effect, and the median survival time of TNBC bearing mice treated with iNGR-modified micelles was significantly extended compared to Taxol. Therefore, this smart micelle system may be a favorable platform for effective TNBC therapy.

• Authors: Yujie Zhang, Yifei Lu, Yu Zhang, Xi He, Qinjun Chen, Lisha Liu, Xinli Chen, Chunhui Ruan, Tao Sun, Chen Jiang
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 14 Issue 10 Pg. 3409-3421 (10 02 2017) ISSN: 1543-8392 [Electronic] United States
• PMID: 28832164 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Dendrimers
• Drug Carriers
• Micelles
• Oligopeptides
• cysteinyl-arginyl-asparagyl-glycyl-arginyl-glycyl-prolyl-aspartyl-cysteine
• Polyethylene Glycols
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Cell Line, Tumor
• Dendrimers (chemistry)
• Drug Carriers (chemistry)
• Drug Liberation
• Female
• Humans
• Mice
• Mice, Nude
• Micelles
• Oligopeptides (chemistry)
• Paclitaxel (pharmacology, therapeutic use)
• Polyethylene Glycols (chemistry)
• Solubility
• Tissue Distribution
• Triple Negative Breast Neoplasms (drug therapy)
• Xenograft Model Antitumor Assays