Novel electrosprayed core-shell polyethyleneimine and phospholipid coated MSNs for Co-delivery of KAZ3 and MDR-1 siRNA for efficient chemotherapy in multidrug-resistant colon cancer

Different strategies and multifunctional nano-carriers have been employed to enhance chemotherapeutic drugs bioavailability and tackle acquired multi-drug resistance (MDR) thus ensuring efficient chemotherapy with fewer adverse effects. Among these, mesoporous Silica Nanoparticles (MSNs) are exciting matrices for improving cytotoxic drugs bioavailability and circumventing MDR through its potential of co-delivery of anticancer agents and short interfering RNA (siRNA). In this study, MSNs were coated with (1:1) Polyethyleneimine (PEI) and phospholipids (PL) composite and were loaded with KAZ3 (Anticancer chalcone) using coaxial electrospraying in a one step process. The novel delivery system was used to co-deliver both MDR-1 siRNA and KAZ3 to colon cancer cell lines in order to knockdown the MDR-1 gene and thus to improve KAZ3 cytotoxicity. The prepared drug/siRNA delivery system was characterized using SEM, fluorescence microscopy, TGA, zeta sizer, actives (KAZ3 and siRNA) loading efficiency, actives release studies, siRNA gel retardation and actives cellular uptake. The cytotoxicity of formulations against cancer cell lines (HCT 116) was also assessed using MTT assay and MDR-1 gene silencing efficiency using western blotting. Results showed that coaxial electrospraying was efficient in preparing core-shell coated MSNs that were able to co-deliver both MDR-1 siRNA and KAZ3 to colon cancer lines. The MSNs coated with PL and 2.5 KDa PEI were found to be more compatible with human cells than to 25KDa PEI coated MSNs. KAZ3/siRNA loaded PEI-PL coated MSNs were successful in decreasing multidrug resistance gene expression to 40 % and causing up to 92 % colon cancer cell death. The findings of the present study show the immense potential of electro-hydrodynamic atomization (EHDA) as a technique for producing drug loaded MSNs based core-shell particles.