Newly acylated SN-38 homodimers: carrier-free nano-prodrugs for chemotherapy

Homodimers based on 7-ethyl-10-hydroxycamptothecin (SN-38) containing S<sub>2</sub>[(CH<sub>2</sub>)<sub>2</sub>OC(O)]<sub>2</sub> bridge and acyl substituents were synthesized and used for fabrication of nano-prodrugs. The latter demonstrated remarkable dispersion and stability over one month when stored at a temperature of 4 °C, with an ideal size of nanoparticles in the range of 80-130 nm that is required for EPR effect. The homodimer containing cyclopropylacetyl substituent chain exhibited significant anticancer efficacy against the HCT-116 and A-549 cell lines, with IC50 values having been 0.07 ± 0.01 and 0.29 ± 0.02 μm, respectively.