Triptolide (TP) is known for its diverse pharmacological activities but also its delivery and toxicity issues. This study aimed at exploiting TP's anticancer effects at lower risk of systemic toxicity by developing local-injectable "bone-targeting TP nanoparticle" (TPN) for bone-only metastasis treatment. The lipid/oil-based TPNs decorated with alendronate (ALE) achieved size of 70.4-111.2 nm with good dispersion stability. The drug encapsulation efficiency reached 97 % and drug release profiles were in biphasic, controlled manner lasting for 5 days in medium with serum proteins and calcium. TPNs were more cytotoxic than free TP against MDA-MB-231 breast cancer cells (IC50: 16.40 ± 0.80 nM vs 25.45 ± 1.83 nM, P < 0.05) but less cytotoxic against MC3T3-E1 osteoblasts (P < 0.05). When combined with paclitaxel or docetaxel, low dose TPN (containing 10 nM) significantly increased the effectiveness of the two chemotherapy drugs against MDA-MB-231 (IC50 values decreased from 7.3 nM to 2.5 nM for docetaxel; from 4.6 nM to 1.1 nM), indicating potent chemosensitization effects. Retardation of in vitro cancer cell migration by TPN was also observed in the standard scratch assay. ALE decoration significantly enhanced the TPN affinity for both calcium hydroxyapatite and porcine bone chip models, which led to enhancement in TP retention in the bones up to 8.1-fold versus free drug. Overall, TPN demonstrated good potential as a local-injectable, bone-targeted nanotherapy tailored for eradication of bone-only metastasis at reduced risk of systemic toxicity.
Keywords: Bone targeting; Breast cancer; Drug delivery; Nanoparticle; Triptolide.
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