María Vallet Regí

Janus Mesoporous Silica Nanoparticles for Dual Targeting of Tumor Cells and Mitochondria

The development of targeted nanocarriers able to be selectively internalized within tumor cells, and therefore to deliver anti-tumor drugs specifically to diseased cells, constitutes one of the most important goals in nano-oncology. Herein, the development of Janus mesoporous silica particles asymmetrically decorated with two targeting moieties, one of them selective for folate membrane cell receptors (folic acid) and the other one able to bind to mitochondria membrane (triphenylphosphine, TPP), is described in order to achieve sequential cell to organelle vectorization. The asymmetric decoration of each side of the particle allows fine control in the targeting attachment process in comparison with the use of symmetric nanocarriers. The presence of folic acid induces a higher increase in particle accumulation inside tumor cells, and once there, these nanocarriers are guided close to mitochondria by the action of the TPP moiety. This strategy can be applied for improving the therapeutic efficacy of current nanomedicines.

Proteolytic enzymes and cavitation as strategies to enhanced penetration of drug nanocarriers

The poor penetration of drug nanocarriers within tumor tissues is one of the most critical factors which limit their effectiveness. Nanomedicine has developed different strategies in order to overcome this important hurdle. Some of these strategies are based on the degradation of the highly dense extracellular matrix (ECM) which is usually present in many solid tumors. In this sense, one of the most promising approaches consists in the nanoparticle decoration with proteolytic enzymes able to digest the ECM favoring its penetration. Other strategy is based on the capacity of ultrasounds to induce cavitation which propels the nanocarriers to deep areas into the tumor. Both strategies have demonstrated significant improvement in the penetration of nanocarriers in malignant tissues, enhancing their effectivity.