Nano-prodrug is a nanomedicine developed by the reprecipitation method, which allows nanoparticles to be fabricated by only prodrug molecules without using any nanocarriers. In the present study, we synthesized a heterodimer, composed of hinokitiol and podophyllotoxin (PPT) linked via different linkers of carbon chain length as new prodrug compounds, and fabricated their nano-prodrugs. We found that the longer the carbon chain linker, the smaller the size of nanoparticles, and the lower their cytotoxicity. We concluded that heterodimeric prodrugs can be fabricated into nano-prodrugs without reducing their drug loading capacity, and might eventually serve as a promising template for the development of novel nanomedicine.