Smart Human-Serum-Albumin-As₂ O₃ Nanodrug with Self-Amplified Folate Receptor-Targeting Ability for Chronic Myeloid...

Area of Science:

• Nanomedicine
• Oncology
• Biochemistry

Background:

• Arsenic trioxide (ATO) is effective for acute promyelocytic leukemia but has dose-limiting toxicities.
• High-dose ATO for other cancers is hindered by severe side effects on healthy organs.
• Targeted drug delivery systems are needed to improve ATO's therapeutic index.

Purpose of the Study:

• To develop a smart nanodrug for targeted delivery of ATO.
• To enhance ATO's efficacy and reduce its toxicity in chronic myeloid leukemia (CML) models.
• To investigate the role of folate receptor-beta (FRβ) in targeted drug uptake.

Main Methods:

• Loading ATO onto folate (FA)-labeled human serum albumin (HSA) using a GSH- and pH-sensitive bond, creating FA-HSA-ATO.
• Utilizing FA-HSA-ATO's specific recognition of FRβ-positive CML cells.
• Evaluating in vitro and in vivo therapeutic efficacy and side effects in CML and xenograft models.

Main Results:

• FA-HSA-ATO demonstrated specific targeting and increased intracellular accumulation of ATO in FRβ+ CML cells.
• The nanodrug upregulated FRβ expression, enhancing further drug recruitment and uptake.
• Significant alleviation of side effects and improved therapeutic efficacy of ATO were observed in CML and xenograft models.

Conclusions:

• FA-HSA-ATO represents a promising targeted nanodrug for enhanced ATO cancer therapy.
• This approach effectively overcomes ATO's toxicity limitations.
• Targeting FRβ offers a viable strategy for improving CML treatment outcomes.