Abstract
A newly developed injectable nanoparticle generator (iNPG) has effectively delivered chemotherapy to lung metastases in mouse models of triple-negative breast cancer, which lacks estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression (Xu R et al. Nat Biotechnol. doi:10.1038/nbt.3506 [published online March 14, 2016]). The system components include a nanoporous biodegradable silicon material and a polymer, poly(l-glutamic acid), that is connected to doxorubicin, a chemotherapeutic agent, via a pH-sensitive cleavable linker (pDox). When intravenously injected into mice, the iNPG-pDox naturally accumulated at sites of metastases due to blood vessel leakiness surrounding tumors. The silicon material then degraded, releasing pDox, which spontaneously formed nanometer-sized particles that were taken up by individual cancer cells. Once inside the cancer cells, the acidic pH close to the nucleus caused the links between doxorubicin molecules and the polymer to break, releasing doxorubicin at a cellular location devoid of drug efflux pumps. High concentrations of doxorubicin were maintained for more than 1 week after administration.
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