Illustration of TMZ (temozolomide) and siRNA conjugated preparation of folic acid decorated Fa-PEG-PEI-PCL and release of antitumor therapeutics inside the cancer cells (a); TEM images showing TMZ-conjugated, folic acid-decorated PEC micelle (left) and TMZ and siRNA-conjugated, folic acid-decorated PEC micelle (right) at pH 7.4. All samples were stained with 0.5% uranyl acetate for 1 min. Scale bar: 200 nm (b); in vitro cytotoxicity effect of different nanocomplexes on C6 cells evaluated by CCK8 assay at various TMZ concentrations. Cells were incubated for 48 h and BCL-2 siRNA concentration used is 20 nM (c); Mean tumor volume determined using magnetic resonance imaging measured after 25 days of the first injection. *P < 0.05 vs TMZ-FaPEC@siRNA; #P < 0.05 vs TMZ-PEC@siRNA; ΔP < 0.05 vs TMZ-FaPEC@SCR (d); visualization of tumor growth inhibition in male Sprague–Dawley rats implanted with C6 cells after treatment with different formulations (red arrow indicates the tumor) (e). Fa, folate; PCL, poly(ε-caprolactone); PEG, poly(ethylene glycol); PEI, poly(ethylenimine); TMZ, temozolomide
(reproduced with permission from [273])