Folate-targeted star-shaped cationic copolymer co-delivering docetaxel and MMP-9 siRNA for nasopharyngeal carcinoma therapy

Abstract

The co-delivery of drug and gene has become the primary strategy in cancer therapy. Based on our previous work, to co-deliver docetaxel (DOC) and MMP-9 siRNA more efficiently for HNE-1 nasopharyngeal carcinoma therapy, a folate-modified star-shaped copolymer (FA-CD-PLLD) consisting of β-cyclodextrin (CD) and poly(L-lysine) dendron (PLLD) was synthesized, and then used for DOC and MMP-9 co-delivery. Different from commonly used amphiphilic copolymers micelles, the obtained CD derivative could be used directly for the combinatorial delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vitro and in vivo assays are carried out to confirm the effectiveness of the target strategy and combined treatment. It was found that the conjugation of CD-PLLD with FA could enhance the DOC/MMP-9 delivery effect obviously, inducing a more significant apoptosis and decreasing invasive capacity of HEN-1 cells. In vivo assays showed that FA-CD-PLLD/DOC/MMP-9 could inhibit HNE-1 tumor growth and decrease PCNA expression effectively, indicating a promising strategy for nasopharyngeal carcinoma therapy. Moreover, the in vivo distribution of DOC and MMP-9, blood compatibility and toxicity are also explored.

Matrix Metalloproteinase Inhibitors as Investigational and Therapeutic Tools in Unrestrained Tissue Remodeling and Pathological Disorders

“…In vivo assays showed that codelivery of docetaxel/MMP-9 siRNA inhibited HNE-1 tumor growth and decreased expression of the cell proliferation marker proliferating-cell nuclear antigen (PCNA), suggesting that it could be a promising strategy for treatment of localized tumors such as nasopharyngeal carcinoma. 318 …”

Preparation and Characterization of Folate-Targeted Fe3O4 Nanoparticle Codelivering Cisplatin and TFPI-2 Plasmid DNA for Nasopharyngeal Carcinoma Therapy

“…Therefore, gene targeting therapy has come into the spotlight in team researches and clinical trials [19][20][21]. Our previous studies have, respectively, developed a cyclodextrin-poly derivative [22] and a folate-targeted cationic copolymer [23] to carry docetaxel and MMP siRNA plasmid for better anti-NPC treatment. In vitro assay demonstrated the superiority of the composites in promoting tumor cell apoptosis and inhibiting their invasion ability.…”

The association of matrix metalloproteinase-9 promoter polymorphisms with gastric cancer risk: a meta-analysis

“…However, other researchers hold a different opinion and the causal mechanism of this imbalance remains unclear. In addition, in the past two years, an increasing number of studies have revealed the relationship between MMP-9 and oesophageal squamous cell carcinoma [ 34 ], ovarian cancer [ 35 ], nasopharyngeal carcinoma [ 36 , 37 ], Ewing sarcoma [ 38 ], and bladder cancer [ 39 ]. Different microenvironments and tissue interactive mechanisms may lead to the presence of the divergence.…”