Two Different Responsive Organosilica Nanocarriers to Combine Chemo- and Immunotherapy against Cancer

Abstract

The combination of chemo- and immunotherapy was recently demonstrated to improve a patient’s response to therapy, giving rise to an emerging cancer treatment known as chemoimmunotherapy (CIT). Despite the promising benefits of CIT, the most important challenges are (i) the simultaneous or time-controlled delivery of two drugs and (ii) the selective uptake into different cells for each of the drugs: cancer cells for the chemotherapeutic and macrophages for the immunostimulation actives. Herein, a delivery strategy based on morphologically different stimuli-responsive breakable organosilica nanocarriers is exploited to transport two distinct drugs in the different cells using different times of delivery. We employ stimulus-sensitive, PEGylated organosilica nanocages to encapsulate the chemotherapeutic agent doxorubicin, which is preferentially taken up by tumor cells vs macrophages. On the other hand, similar size mesoporous organosilica nanoparticles, preferentially internalized by macrophages, are filled with the immunostimulator resiquimod. The administration in a sequential manner of the two different nanocarriers allowed us to assess the integrated effect of the combined therapy versus treatment with a single drug. In vitro work clearly shows an important reduction of tumor cell viability when both chemo- and immunotherapeutic agents are delivered.