Nanoparticle-Based Combination Therapy for Ovarian Cancer.

Abstract

Ovarian cancer is one of the most common malignant tumors in gynecology with a high incidence. Combination therapy, eg, administration of paclitaxel followed by a platinum anticancer drug is recommended to treat ovarian cancer due to its advantages in, eg, reducing side effects and reversing (multi)drug-resistance compared to single treatment. However, the benefits of combination therapy are often compromised. In chemo and chemo/gene combinations, co-deposition of the combined therapeutics in the tumor cells is required, which is difficult to achieve due to dramatic pharmacokinetic differences between combinational agents in free forms. Moreover, some undesired properties such as the low-water solubility of chemodrugs and the difficulty of cellular internalization of gene therapeutics also hinder the therapeutic potential. Delivery of dual or multiple agents by nanoparticles provides opportunities to tackle these limits. Nanoparticles encapsulate hydrophobic drug(s) to yield aqueous dispersions facilitating its administration and/or to accommodate hydrophilic genes facilitating its access to cells. Moreover, nanoparticle-based therapeutics can not only improve drug properties (eg, in vivo stability) and ensure the same drug disposition behavior with controlled drug ratios but also can minimize drug exposure of the normal tissues and increase drug co-accumulation at targeted tissues via passive and/or active targeting strategies. Herein, this work summarizes nanoparticle-based combination therapies, mainly including anticancer drug-based combinations and chemo/gene combinations, and emphasizes the advantageous outcomes of nanocarriers in the combination treatment of ovarian cancer. In addition, we also review mechanisms of synergetic effects resulting from different combinations.