Advances and challenges in the use of nanoparticles to optimize PK/PD interactions of combined anti-cancer therapies.

Combination chemotherapy has become the primary strategy for treating cancer; however, the clinical success of combination treatments is limited by the distinct pharmacokinetics (PK) of different drugs, which lead to nonuniform distribution and an inability to coordinate dosing regimes at the site of the tumor. In the first half of this review, we will discuss the recent development of nanoparticlebased combination strategies to overcome these limitations. Nanoparticles are able to co-encapsulate and carry multiple drugs with different hydrophobicities while maintaining precise ratiometric loading and delivery. They can also temporally sequence the release of multiple drugs and reduce undesirable PK interactions. In the second half of this review, we will touch on the key factors that affect nanoparticle stability and distribution. Nanoparticles provide a promising strategy to improve combinatorial cancer treatments by better controlling PK and metabolic differences between drugs.