Antitumor conjugates with polyamine vectors and their molecular mechanisms

A polyamine conjugate is a special polyamine derivative composed of polyamine vectors appended directly or by a linker to a cargo with specific biological functions. In recent years, extensive researches have emphasized the fact that polyamine conjugates acting as promising antitumor candidates are becoming increasingly important in the polyamine field.

Two key subjects are illustrated in this review. First, various drug-polyamine conjugates and relevant structure-activity relationships are discussed with a focus on the molecular recognition of polyamine transport system (PTS). Second, the design of polyamine conjugates is following a rational mechanism-based strategy. Therefore, it is critically important to understand the intrinsic properties of PTS on the cell membrane, enhanced pharmacological effects of polyamine vector on cellular components, and resulting comprehensive signaling networks.

A general design strategy of polyamine conjugates as well as recent progress in both fundamental mechanism studies and preclinical therapies are provided for the readers.

The multiple functions of polyamine moieties in objective conjugates furnish broad development space for more efficacious antitumor agents.