1. Ratiometric co-encapsulation and co-delivery of doxorubicin and paclitaxel by tumor-targeted lipodisks for combination therapy of breast cancer.
- Author
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Feng C, Zhang H, Chen J, Wang S, Xin Y, Qu Y, Zhang Q, Ji W, Yamashita F, Rui M, and Xu X
- Subjects
- Animals, Antineoplastic Combined Chemotherapy Protocols pharmacology, Doxorubicin administration & dosage, Drug Synergism, Female, Humans, Hydrogen-Ion Concentration, Hydrophobic and Hydrophilic Interactions, Lipids chemistry, MCF-7 Cells, Mice, Mice, Nude, Paclitaxel administration & dosage, Xenograft Model Antitumor Assays, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Breast Neoplasms drug therapy, Drug Delivery Systems, Nanoparticles
- Abstract
Combination therapy is a promising treatment for certain advanced drug-resistant cancers. Although effective inhibition of various tumor cells was reported in vitro, combination treatment requires improvement in vivo due to uncontrolled ratiometric delivery. In this study, a tumor-targeting lipodisk nanoparticle formulation was developed for ratiometric loading and the transportation of two hydrophobic model drugs, doxorubicin (DOX) and paclitaxel (PTX), in one single platform. Furthermore, a slightly acidic pH-sensitive peptide (SAPSP) incorporated into lipodisks effectively enhanced the tumor-targeting and cell internalization. The obtained co-loaded lipodisks were approximately 30 nm with a pH-sensitive property. The ratiometric co-delivery of two drugs via lipodisks was confirmed in both the drug-resistant MCF-7/ADR cell line and its parental MCF-7 cell line in vitro, as well as in a tumor-bearing mouse model in vivo compared with a cocktail solution of free drugs. Co-loaded lipodisks exerted improved cytotoxicity to tumor cells in culture, particularly to drug-resistant tumor cells at synergistic drug ratios. In an in vivo xenograft mouse model, the anti-tumor ability of co-loaded lipodisks was evidenced by the remarkable inhibitory effect on tumor growth of either MCF-7 or MCF-7/ADR tumors, which may be attributed to the increased and ratiometric accumulation of both drugs in the tumor tissues. Therefore, tumor-specific lipodisks were crucial for the combination treatment of DOX and PTX to completely exert a synergistic anti-cancer effect. It is concluded that for co-loaded lipodisks, cytotoxicity data in vitro could be used to predict their inhibitory activity in vivo, potentially enhancing the clinical outcome of synergistic therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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