Compartment-restricted and rate-controlled dual drug delivery system using a biosilica-enveloped ferritin cage

Abstract

Combinational therapy has been exploited to enhance therapeutic efficiency against cancer by overcoming drug resistance and side-effects or by synergistic effects of multi drugs. However, the conventional co-delivery of combination regimens is often limited by the differences in physicochemical properties among different drugs. Here, to solve this problem, we demonstrated an advanced dual drug delivery system (dDDS) using a R5 peptide-fused ferritin (R5FT). Since the fused R5 can mediate biosilica deposition on the ferritin surface (SiO2/R5FT), we could load two types of molecules into the core inside (ferritin cage) and the shell outside (biosilica matrix), respectively. Doxorubicin (Dox) was loaded into the cage by the reassembly of R5FT to obtain R5FT(Dox), and then the monomeric red fluorescent protein (mRFP) or paclitaxel (PTX) was captured in situ by biosilica matrix formation to prepare SiO2(mRFP)/R5FT(Dox) or SiO2(PTX)/R5FT(Dox). The captured mRFP or PTX in the shell exhibited a short-term release, while Dox in the core showed a long-term sustained release. This dDDS with the additional release of PTX decreased the IC50 value of Dox by twofold compared to the use of only Dox in dDDS. The compartment-restricted and rate-controlled dDDS using biosilica-enveloped ferritin cage can provide more efficient combinational drug therapies.