Jump to main content
Jump to site search

Issue 7, 2018
Previous Article Next Article

Integration of phospholipid-hyaluronic acid-methotrexate nanocarrier assembly and amphiphilic drug–drug conjugate for synergistic targeted delivery and combinational tumor therapy

Author affiliations

Abstract

Combinational cancer therapy has been considered as a promising strategy to achieve synergetic therapeutic effects and suppression of multidrug resistance. Herein, we adopted a combination of methotrexate (MTX), an antimetabolite acting on cytoplasm, and 10-hydroxycamptothecin (HCPT), an alkaloid acting on nuclei, to treat cancer. Given the different solubilities, membrane permeabilities, and anticancer mechanisms of both drugs, we developed a dual-targeting delivery system based on 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-hyaluronic acid (a principal ligand of CD44 receptors)-MTX (a selective ligand of folate receptors) nanoparticles, which was exploited to carry HCPT–MTX conjugate for synergistically boosting dual-drug co-delivery. The HCPT–MTX conjugate was synthesized by a blood-stable yet intracellularly hydrolysable ester bond. The core–shell-corona DSPE–HA–MTX nanoparticles encapsulating HCPT–MTX (HCPT–MTX@DHM) exhibited high drug entrapment efficiency (∼91.8%) and pH/esterase-controlled release behavior. Cellular uptake studies confirmed significant increase in the efficiency of selective internalization of HCPT–MTX@DHM via CD44/folate receptors compared with those of DSPE–HA nanoparticles encapsulating HCPT–MTX (HCPT–MTX@DH), both drugs, or each individual drug. Furthermore, in vivo near-infrared fluorescence and photoacoustic dual-modal imaging indicated that DiR-doped HCPT–MTX@DHM nanoparticles efficiently accumulated at the tumor sites through passive-plus-active targeting. Finally, the synergistic active targeting and synchronous dual-drug release at a synergistic drug-to-drug ratio resulted in highly synergetic tumor cell-killing and tumor growth inhibition in MCF-7 tumor-bearing mice. Therefore, HCPT–MTX@DHM nanoparticles can be an efficient and smart platform for tumor-targeting therapy.

Graphical abstract: Integration of phospholipid-hyaluronic acid-methotrexate nanocarrier assembly and amphiphilic drug–drug conjugate for synergistic targeted delivery and combinational tumor therapy

Back to tab navigation

Supplementary files

Publication details

The article was received on 03 Jan 2018, accepted on 07 May 2018 and first published on 08 May 2018


Article type: Paper
DOI: 10.1039/C8BM00009C
Citation: Biomater. Sci., 2018,6, 1818-1833
  •   Request permissions

    Integration of phospholipid-hyaluronic acid-methotrexate nanocarrier assembly and amphiphilic drug–drug conjugate for synergistic targeted delivery and combinational tumor therapy

    Y. Li, H. Zhang, Y. Chen, J. Ma, J. Lin, Y. Zhang, Z. Fan, G. Su, L. Xie, X. Zhu and Z. Hou, Biomater. Sci., 2018, 6, 1818
    DOI: 10.1039/C8BM00009C

Search articles by author

Spotlight

Advertisements