Abstract: The process to load doxorubicin(DOX)was optimized using all-trans-retinoid acid(ATRA)-modified low molecular weight heparin(LMWH)nanoparticles, and the in vitro characterization of DOX-loaded micelles was investigated. LMWH-ATRA conjugates(LHR)was synthesized through amide condensation reaction between LMWH and all-trans-retinoid acid(ATRA). The DOX-loaded LHR micelles were prepared by dialysis and characterized by particle size, zeta potential, drug loading content and entrapment efficiency. In vitro release of DOX from micelles was investigated in different buffer solutions(pH 4. 5, 5. 8 and 7. 4). MCF-7 cells were used to assess the cellular uptake of DOX-loaded LHR micelles. Cell apoptosis induced by DOX-loaded micelles was evaluated in MCF-7 cells by flow cytometry. LHR conjugates could encapsulate DOX up to 18. 7%, with an entrapment efficiency of 78. 8%. The particle size of negatively charged DOX-loaded micelles was in the range of 112. 1-153. 0 nm. In vitro release of DOX was faster in acidic enviroment, indicating the drug-loaded micelles were pH-sensitive. The DOX-loaded micelles were easily uptaken by MCF-7 cells compared with free DOX, and DOX/LHR micelles could induce the apoptosis of MCF-7 cells showing cytotoxicity. DOX-loaded micelles exhibited good physico-chemical properties and anti-tumor activities in vitro, indicating that LHR ploymers were proper carriers for DOX with enhanced anti-tumor activities.