Combined Ultrasound Treatment with Transferrin-Coupled Nanoparticles Improves Active Targeting of 4T1 Mammary Carcinoma Cells

Abstract

Objective: Conventional chemotherapy remains the mainstay treatment for many breast cancer patients, but its effectiveness is limited by toxic side effects. Incorporating drugs such as docetaxel into nanoparticle medicines can reduce toxicity but further improvements are required. To facilitate more active tumor targeting, we prepared transferrin-docetaxel-loaded pegylated-albumin nanoparticles (Tf-PEG-DANPS). Methods: The growth inhibitory effects and the ability of unmodified DANPS or PEG-DANPS to induce apoptosis in 4T1 mouse mammary cancers were compared to Tf-PEG-DANPS treatment using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry. These experiments were extended in vivo to the intravenous treatment of 4T1 tumors where PEG-DANPS was compared to Tf-PEG-DANPS alone or Tf-PEG-DANPS combined with ultrasound (US + Tf-PEG-DANPS). Histological assessments using hematoxylin and eosin (HE) sections were performed to examine antitumor activity, metastasis to lung and liver, and body weight measurements taken as an indicator of toxicity. Results: MTT experiments show that, in the normal and low concentration interval, the inhibition ability of the Tf-PEG-DANPS is higher than that of other drug-giving groups, and the flow cytometry show that the proportion of induced apoptosis in each given group is 2.88%, 42.95%, 48.23%, and 57.89%, indicating that the Tf-PEG-DANPS group has more significant ability to induce apoptosis than other drug-giving groups. From the pathological HE staining and semiquantitative analysis, US+Tf-PEG-DANPS can effectively inhibit the growth of breast cancer transplanted tumors and suppress metastases, it also has smaller toxic side effects on mice. Conclusion: The antitumor effect of US+Tf-PEG-DANPS represents an effective combination that exhibits increased antitumor activity and metastasis reduction with an improved side-effect profile.