Anti-CD33 antibody enhances liposomal co-delivery of cytarabine and daunorubicin for targeted combination chemotherapy

The combination chemotherapy of cytarabine and daunorubicin (7 + 3 standard regimen) has stood as the mainstay treatment against acute myeloid leukemia for decades. Recent advances in nanomedicine have led to the development of Vyxeos®, a liposomal formulation of cytarabine/daunorubicin fixed in a synergistic 5:1 molar ratio. The synchronized pharmacokinetics and biodistribution of the partner chemotherapeutic agents in Vyxeos® contribute to a significantly higher complete remission rate compared to the traditional 7 + 3 regimen. However, Vyxeos® did not markedly enhance the safety profile, exhibiting similar types and severities of adverse events. To mitigate adverse reactions as well as intensify 7 + 3 combination chemotherapy, we leveraged a functionalization strategy, engineering a humanized anti-CD33 antibody-modified liposome carrier to actively co-deliver cytarabine and daunorubicin. Differing from DSPC/DSPG-based liposomal formulation of Vyxeos®, we developed a PEGylated HSPC liposome with high cholesterol content to proportionally co-load the two agents. Surface reaction via maleimide-thiol chemistry realized anti-CD33 antibody functionalization, demonstrating superior in-vivo therapeutic efficacy compared to plain liposomal drug formulations (p < 0.001) and moderately reduced non-specific adverse effects in the heart and kidneys.