Polymalic acid for translational nanomedicine

With rich carboxyl groups in the side chain, biodegradable polymalic acid (PMLA) is an ideal delivery platform for multifunctional purposes, including imaging diagnosis and targeting therapy. This polymeric material can be obtained via chemical synthesis, or biological production where L-malic acids are polymerized in the presence of PMLA synthetase inside a variety of microorganisms. Fermentative methods have been employed to produce PMLAs from biological sources, and analytical assessments have been established to characterize this natural biopolymer. Further functionalized, PMLA serves as a versatile carrier of pharmaceutically active molecules at nano scale. In this review, we first delineate biosynthesis of PMLA in different microorganisms and compare with its chemical synthesis. We then introduce the biodegradation mechanism PMLA, its upscaled bioproduction together with characterization. After discussing advantages and disadvantages of PMLA as a suitable delivery carrier, and strategies used to functionalize PMLA for disease diagnosis and therapy, we finally summarize the current challenges in the biomedical applications of PMLA and envisage the future role of PMLA in clinical nanomedicine. GRAPHICAL ABSTRACT: [Image: see text]