Dual-responsive nanoparticles loading bevacizumab and gefitinib for molecular targeted therapy against non-small cell lung cancer.

The combination of vascular endothelial growth factor (VEGF) inhibitors and tyrosine kinase inhibitors (TKIs) is newly available for molecular targeted therapy against non-small cell lung cancer (NSCLC) in clinic. However, the therapeutic benefits remain unsatisfying due to the poor drug delivery to targets of interest. In this study, we developed bevacizumab-coated gefitinib-loaded nanoparticles (BCGN) with dual-responsive drug release for inhibiting tumor angiogenesis and phosphorylation of epidermal growth factor receptor (EGFR). Through an exogenous corona strategy, bevacizumab is easily coated on gefitinib-loaded nanoparticles via electrostatic interaction. After intravenous injection, BCGN are efficiently accumulated in NSCLC tumors as confirmed by dual-model imaging. Bevacizumab is released from BCGN upon oxidation in tumor microenvironment, whereas gefitinib is released after being internalized by tumor cells and disassembled in reduction cytoplasm. The dual-responsive release of bevacizumab and gefitinib significantly inhibits tumor growth in both A549 and HCC827 human NSCLC models. Our approach provides a promising strategy to improve combinational molecular targeted therapy of NSCLC with precisely controlled drug release.

Treating breast cancer metastasis with cabazitaxel-loaded polymeric micelles.

Cancer metastasis is the primary cause of high mortality in breast cancer patients. In this study, we loaded an anti-cancer drug, cabazitaxel (CTX), into polymeric micelles (CTX-loaded polymeric micelles, PCMs), and explored their therapeutic efficacy in breast cancer metastasis. The characteristics of PCMs were investigated, and their anti-metastatic efficacy was assessed using in vitro and in vivo evaluations. PCMs had an average diameter of 50.13±11.96 nm with a CTX encapsulation efficiency of 97.02%±0.97%. PCMs could be effectively internalized into metastatic 4T1 breast cancer cells in vitro. CTX (10 ng/mL) or an equivalent concentration in PCMs did not significantly affected the viability of 4T1 cells, but dramatically decreased the cell migration activities. In an orthotopic metastatic breast cancer model, intravenously administered PCMs could be efficiently delivered to the tumor sites, resulting in a 71.6% inhibition of tumor growth and a 93.5% reduction of lung metastases. Taken together, our results verify the anti-metastatic efficacy of PCMs, thus providing an encouraging strategy for treating breast cancer metastasis.