Doxorubicin-Loaded Polyelectrolyte Multilayer Capsules Modified with Antitumor DR5-Specific TRAIL Variant
Carriers providing active targeted delivery of anticancer drugs to tumor cells are promising for cancer chemotherapy. A team of scientists from the Laboratory of protein engineering and the Laboratory of Biomedical Materials IBCh RAS in collaboration with collegues from other Russian Institutes have developed biodegradable polyelectrolyte microcapsules which have been modified with the DR5-B ligand.
In this work, biodegradable polyelectrolyte capsules with an average size of 300 and 500 nm based on dextran sulfate and poly-L-arginine were obtained using layer-by-layer technique. The capsules were modified with a promising ligand, namely the DR5-B protein, an analogue of the cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The latter is known to specifically bind to the DR5 death receptor overexpressed on the tumor (but not normal) cell surface. Thus, it can be used for targeted drug delivery to tumor cells, while triggering cell apoptosis. In addition, the capsules were loaded with the anti-cancer drug doxorubicin (DOX) in a subtoxic concentration, and then characterized in terms of their size, ζ-potential, DOX encapsulation and release efficiencies, as well as the ability to bind the DR5-B protein.
Capsules internalization (uptake) by cells depending on the size and surface modification by the DR5-B protein was studied using confocal microscopy, flow cytometry and fluorimetry, while capsules cytotoxicity was evaluated with MTT-test. All experiments were performed using two in vitro models, namely 2D (monolayer cell culture) and 3D (tumor spheroids), which were obtained from human colorectal carcinoma HCT-116 cells. Thus, the capsules could be proposed as a new effective system for targeted anticancer drug delivery. The system provides both targeted drug delivery only to tumor (but not normal) cells due to the DR5-B protein, as well as a synergistic anticancer effect due to the anticancer activity of both DR5-B and DOX. It should be mentioned that the DOX side effects could be reduced, since the capsules were loaded with subtoxical DOX concentration.
The results are published in the Nanomaterials.