A poly(trimethylene carbonate) derivative with a methoxyethoxyl group, poly[5-(2-methoxyethyoxymethyl)-5-methyl-1,3-dioxan-2-one] (poly(TMCM-MOE1OM)), was used as a block copolymer component with polylactide. The hydrophilic properties of the poly(TMCM-MOE1OM) segment resulted in nanoparticles with acetonitrile/water through a self-organized precipitation process. Wide applications of the obtained nanoparticles are expected owing to the biodegradability of both the interior and exterior parts, which are composed of different polymer backbones.