Background: Integrins are heterodimeric cell surface receptors that mediate cell-cell and
cell-extracellular matrix adhesion. These molecules play a role in processes such as cell growth and
proliferation, differentiation, migration, cell trafficking, besides contributing to angiogenesis and tumor
development. Given their biological role, integrins have been proposed as amenable targets in medicinal
chemistry. In particular, αvβ3, αvβ5, αvβ6 and α5β1, integrins involved in tumor angiogenesis and
metastasis, have been the subject of studies aimed at the discovery of novel cancer therapeutics. A large
number of peptides and peptidomimetics based on the RGD (Arg-Gly-Asp) recognition sequence were
developed in the past two decades as integrin ligands. Though such ligands have not been satisfactory
as anti-angiogenic agents, their use as tools to achieve selective tumor targeting of anticancer drugs has
Objective: In this review, we summarize recent literature and patent applications in which integrin peptidic
and peptidomimetic ligands were conjugated to chemotherapeutic agents both with stable or cleavable
bonds to achieve tumor targeted drug delivery.
Methods: Relevant recent patents and literature in this field have been considered spanning the search
from 2000 to 2016. Literature and patents were examined according to the different classes of cytotoxic
drug targeted to integrins.
Conclusion: In spite of the promising features of the conjugates, none of them has entered clinical trials.
New efforts are focused on innovative approaches in the field such as the synthesis of new integrin ligands
able to target a single integrin type or the employment of nanoparticles based drug delivery systems.