Lysosome-Independent Intracellular Drug/Gene Codelivery by Lipoprotein-Derived Nanovector for Synergistic Apoptosis-Inducing Cancer-Targeted Therapy.

Abstract

In this paper, reconstituted high-density lipoprotein (rHDL), a lipoprotein-derived nanovector, was constructed for codelivery of paclitaxel (PTX) and wild-type p53 gene (p53). The particle size and the zeta potential of PTX-DODAB/p53-rHDL nanoparticles were 177.2 nm and -20.06 mV, respectively. Meanwhile, they exhibited great serum stability and satisfactory sustained release characteristics in vitro. PTX-DODAB/pDNA-rHDL nanoparticles simultaneously improved the cellular uptake of PTX and pDNA via scavenger receptor B type I (SR-BI) mediated lysosome-independent internalization and promoted the transfection of pDNA in MCF-7 cells, which were revealed by flow cytometry and confocal laser scanning microscopy analyses. The high p53 protein expression in MCF-7 cells after rHDL-mediated transfection was detected by Western blotting assay. Moreover, PTX-DODAB/p53-rHDL nanoparticles showed superior cytotoxicity and significantly induced apoptosis in SR-BI overexpressed MCF-7 cells. In in vivo studies, PTX-DODAB/p53-rHDL nanoparticles without obvious toxic effects to vessels, blood, or major organs exhibited efficient tumor targeting and encouraging antitumor effects on tumor-bearing nude mice compared with controls. All the results above indicated that PTX-DODAB/p53-rHDL nanoparticles held broad prospects in combination of chemotherapeutics and gene therapeutic agents for cancer-targeted therapy.

• Authors: Wei Wang, Kerong Chen, Yujie Su, Jielei Zhang, Min Li, Jianping Zhou
• Journal: Biomacromolecules (Biomacromolecules) Vol. 19 Issue 2 Pg. 438-448 (02 12 2018) ISSN: 1526-4602 [Electronic] United States
• PMID: 29334216 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Lipoproteins, HDL
• Quaternary Ammonium Compounds
• Tumor Suppressor Protein p53
• dimethyldioctadecylammonium
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Apoptosis
• Female
• Genetic Therapy (methods)
• Humans
• Lipoproteins, HDL (chemistry)
• MCF-7 Cells
• Mammary Neoplasms, Experimental (drug therapy, therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles (adverse effects, chemistry)
• Paclitaxel (administration & dosage, therapeutic use)
• Quaternary Ammonium Compounds (chemistry)
• Tumor Suppressor Protein p53 (genetics, metabolism)