HPMA copolymers for modulating cellular signaling and overcoming multidrug resistance

Unique properties of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer granted its wide use as a carrier for different nanotherapeutics. However, the role of HPMA in a drug delivery system is not limited solely to a carrier for an active payload. Detailed investigations revealed its deep influence on the molecular mechanisms of antitumor action of chemotherapeutic drugs bound to HPMA copolymer. Such influence involves changing the internalization and intracellular trafficking of an entire HPMA-drug complex, modifying the topography of the accumulation of delivered anticancer drug in the tumor and inside tumor cells, overcoming and suppression of existing drug resistance and preventing its de novo development, inhibition of cellular drug detoxification and intracellular repair mechanisms, affecting cell death signaling pathways and mechanisms of apoptosis and necrosis induction. The present review underlines the major mechanisms of the aforementioned effects leading to the substantial enhancement of cell death-inducing ability of conjugated anticancer drugs.