Cytarabine (Ara-C) is an essential medicine used in the clinical treatment of acute lymphoblastic leukemia. However, Ara-C suffers from high hydrophilicity, rapid plasma degradation and significant side effects. Thus, herein, to eliminate the limitations of Ara-C in the treatment of leukemia, Sgc8 aptamer targeting and glutathione (GSH)-responsive polymeric micelles (PCL-ss-Ara@Sgc8-BSA) were prepared. The prodrug was synthesized via covalent bond formation between acryloyl chloride-terminal PCL-ss-PCL and Ara-C, and surface decoration with Sgc8-bovine serum albumin (Sgc8-BSA). The obtained PCL-ss-Ara@Sgc8-BSA exhibited good GSH-responsive drug release behavior, obvious targetability and sufficient antitumor effect to acute lymphoblastic leukemia (ALL) cells (CCRF-CEM). A hemolysis test was further carried out to demonstrate that these polymeric micelles are safe to be administrated intravenously. Compared with free Ara-C, PCL-ss-Ara@Sgc8-BSA significantly enhanced tumor growth inhibition in mice bearing CCRF-CEM xenograft tumors, while causing little side effects, and improved the survival rate of CCRF-CEM tumor-bearing mice in vivo. Therefore, this new self-assembling small molecular prodrug equipped with Sgc8 targeting function is a potential treatment for the targeted therapy of acute lymphoblastic leukemia.
Keyphrases
- cancer therapy
- acute lymphoblastic leukemia
- drug release
- drug delivery
- allogeneic hematopoietic stem cell transplantation
- acute myeloid leukemia
- bone marrow
- gold nanoparticles
- high dose
- adipose tissue
- induced apoptosis
- metabolic syndrome
- low dose
- cell proliferation
- combination therapy
- endoplasmic reticulum stress
- oxidative stress
- red blood cell
- replacement therapy
- magnetic nanoparticles