pH-responsive delivery of Platinum-based drugs through the surface modification of heparin on mesoporous silica nanoparticles

Although Platinum-based drugs such as cisplatin, carboplatin, oxaliplatin play vital roles in chemotherapy treatment of various malignant tumors, their application and clinical efficiency are limited due to the toxicity and resistance. In this study, a drug delivery system based on mesoporous silica nanoparticles modified with heparin, a polymer consists of excessive amounts of carboxylic groups being able to coordinate with platin atoms, was fabricated to ensure a sustainable and pH-responsive release of Platinum-based drug. Heparin modified MSNs (MSN-Hep) were synthesized by Stober method, conjugated via primary amine group on particles' surface, and then characterized. SEM images showed high uniform spherical particles with 89.03 +/- 4.49 nm in diameter. After modification, loading capacity of MSN-Hep was 131 mg cisplatin (a model Platinum-based drug) per 1 g MSN-Hep, twice as the bare MSNs' figure. The amount of drug released in pH 5.8 (tumor microenvironment) was significantly higher compared to that of drug released in pH 7.4 (physiological environment). Finally, Resazurin assay indicated that MSN-Hep was a biocompatible nanocarrier which had no toxicity on MCF-7 cells. These results demonstrated that MSN-Hep could be a great potential nanocarrier in chemotherapy with effectively loading ability and sustained release of Platinum-based drugs with pH response.

Automated summary

In this study, a drug delivery system based on mesoporous silica nanoparticles modified with heparin was fabricated to achieve sustainable and pH-responsive release of Platinum-based drugs. The modified nanoparticles showed high uniform spherical shape with a diameter of 89.03 +/- 4.49 nm, and had a loading capacity of cisplatin twice as the bare nanoparticles. The amount of drug released in tumor microenvironment (pH 5.8) was significantly higher than that released in physiological environment (pH 7.4). Cell toxicity assay confirmed the biocompatibility of the modified nanoparticles on MCF-7 cells. These results suggest that the heparin-modified nanoparticles have great potential as nanocarriers for chemotherapy with effectively loading ability and sustained release of Platinum-based drugs with pH response.