Biodegradable cationic nanoparticles loaded with an anticancer drug for deep penetration of heterogeneous tumours
To enhance limited drug penetration that mediated drug resistance and heterogeneity within the tumour microenvironment, we designed a paclitaxel (PTX) loaded degradable cationic nanogel (DpNG) consisted with acetylated pullulan and low molecular weight polyethyleneimine (LowbPEI, 1.8 kDa). The restoration of cationic charge on the DpNG was achieved via HA degradation by hyaluronidase which is secreted in tumour. The size and surface charge of HA-coated DpNG loaded with PTX (HA/DpNG-PTX) was 200–250 nm and 0 mV, respectively. The DpNG-PTX was showed significant cytotoxicity in heterogeneous cancer cells. The IC50 value of DpNG-PTX was 100 times less than that of free PTX. The growth of heterogeneous tumour in Balb/c mice was inhibited via intravenous injection of HA/DpNG-PTX. Furthermore, the invasive distance and amount of HA/DpNG-PTX localised within the deep tissue regions were increased two times than that of PA-PTX. Therefore, the DpNG based drug delivery system could be useful for treatment of heterogeneous tumour.
Journal: Biomaterials - Volume 34, Issue 31, October 2013, Pages 7674–7682