Dual delivery of nucleic acids and PEGylated-bisphosphonates via calcium phosphate nanoparticles

被引:20
作者
Bisso, Sofia [1 ]
Mura, Simona [2 ]
Castagner, Bastien [3 ]
Couvreur, Patrick [2 ]
Leroux, Jean-Christophe [1 ]
机构
[1] Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Inst Pharmaceut Sci, Zurich, Switzerland
[2] Univ Paris Saclay, Univ Paris Sud, Fac Pharm, Inst Galien Paris Sud,UMR 8612,CNRS, 5 Rue Jean Baptiste Clement, F-92296 Chatenay Malabry, France
[3] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada
基金
欧盟地平线“2020”; 加拿大自然科学与工程研究理事会;
关键词
Nanoparticles; Transfection; Calcium phosphate; Gene delivery; Bisphosphonates; pH-sensitive; NITROGEN-CONTAINING BISPHOSPHONATES; PLASMID DNA; SIRNA; PH; TRANSFECTION; RELEASE; FUNCTIONALIZATION; HYDROXYAPATITE; EXPRESSION; EFFICIENCY;
D O I
10.1016/j.ejpb.2019.06.013
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Despite many years of research and a few success stories with gene therapeutics, efficient and safe DNA delivery remains a major bottleneck for the clinical translation of gene-based therapies. Gene transfection with calcium phosphate (CaP) nanoparticles brings the advantages of low toxicity, high DNA entrapment efficiency and good endosomal escape properties. The macroscale aggregation of CaP nanoparticles can be easily prevented through surface coating with bisphosphonate conjugates. Bisphosphonates, such as alendronate, recently showed promising anticancer effects. However, their poor cellular permeability and preferential bone accumulation hamper their full application in chemotherapy. Here, we investigated the dual delivery of plasmid DNA and alendronate using CaP nanoparticles, with the goal to facilitate cellular internalization of both compounds and potentially achieve a combined pharmacological effect on the same or different cell lines. A pH-sensitive poly(ethyleneglycol)-alendronate conjugate was synthetized and used to formulate stable plasmid DNA-loaded CaP nano-particles. These particles displayed good transfection efficiency in cancer cells and a strong cytotoxic effect on macrophages. The in vivo transfection efficiency, however, remained low, calling for an improvement of the system, possibly with respect to the extent of particle uptake and their physical stability.
引用
收藏
页码:142 / 152
页数:11
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