Targeting the CD44 receptor with hyaluronic acid-modified SWCNTs for 17-hydroxy-jolkinolide B delivery to inhibit breast cancer metastasis

17-Hydroxy-jolkinolide B (HJB), an active ingredient extract from Euphorbia fischeriana Steud., has attracted much attention due to its high efficiency and low toxicity in cancer treatment. However, its clinical potential is compromised by low bioavailability and poor tumor targeting. We developed hyaluronic acid (HA) modified single-walled carbon nanotubes (SWCNTs) for CD44 receptor-mediated targeted delivery of HJB to enhance tumor targeting and therapeutic efficacy. The generated HA-SWCNTs-HJB measured 363.9 ± 12.8 nm in size with a HJB encapsulation efficiency of 61.5 %. HA-SWCNTs-Cou6 was effectively internalized into 4 T1 cells by receptor-mediated endocytosis, exhibiting a 4.23-fold increase compared to passive targeting SWCNTs-Cou6. Moreover, HA-SWCNTs-HJB exhibited higher cytotoxicity against 4 T1 cells than SWCNTs-HJB. The IC₅₀ values at 48 h were 3.9 ± 0.5 and 5.7 ± 0.5 μM, respectively. In vivo fluorescence imaging revealed enhanced tumor accumulation in 4 T1 breast cancer-bearing mice due to CD44 receptor-mediated active targeting. Additionally, HA-SWCNTs-HJB significantly inhibited the tumor growth and suppressed breast cancer metastasis without noticeable side effects in vivo. Overall, our newly developed HJB delivery system HA-SWCNTs-HJB, may be a potential therapeutic strategy for effectively treating breast cancer growth and metastasis.