Layer-by-Layer Assemblies for Cancer Treatment and Diagnosis

Abstract

The layer-by-layer (LbL) technique was introduced in the early 1990s. Since then, it has undergone a series of technological developments, making it possible to engineer various theranostic platforms, such as films and capsules, with precise control at the nanometer and micrometer scales. Recent progress in the applications of LbL assemblies in the field of cancer therapy, diagnosis, and fundamental biological study are highlighted here. The potential of LbL-based systems as drug carriers is discussed, especially with regard to the engineering of innovative stimuli-responsive systems, and their advantageous multifunctionality in the development of new therapeutic tools. Then, the diagnostic functions of LbL assemblies are illustrated for detection and capture of rare cancer cells. Finally, LbL-mimicking extracellular environments demonstrate the emerging potential for the study of cancer cell behavior in vitro. The advantages of LbL systems, important challenges that need to be overcome, and future perspectives in clinical practice are then highlighted.

Keywords: cancer; cellular behaviors; diagnosis; drug delivery; layer-by-layer.

Figure 1. Three examples of co-delivery systems based on the LbL technique.

(A) LbL liposomal nanoparticles (LbL-LNPs) manufactured for a dual-drug delivery system with doxorubicin (DOX) loaded into the core and mitoxantrone (MTX) on to the shell layers;[30] (B) LbL degradable polymer coatings on AuNPs for the simultaneous co-delivery of DNA and siRNA;[31] (C) The co-delivery of siRNA and doxorubicin using the modular DOX-liposome/PLA/siRNA/PLA/HA LbL nanoparticle platform (Left); Release profile of the two therapeutic components (Right).[25]

Figure 2. Diagrams of recent developments in stimuli-responsive LbL systems for drug delivery.

(A) pH-induced DOX release from adamantine-doxorubicin (AD-Dox) loaded LbL hollow microcapsules made by polyaldenhyde dextran-graft-adamantane (PAD-g-AD) and carboxymethyl dextran-graft-β-cyclodextran (CMD-g-β-CD);[34] (A’) The LbL film at the surface of mesoporous silica nanoparticles (MSNs) operated by lowering the pH value to regulate the release of cargo, i.e., DOX or propidium iodide (PI);[35] (B) Temperature-triggered “on-demand” DOX release from LbL films containing temperature-responsive micelles;[37] (C) Light-triggered drug release from (PLL/BSA)₁₀-DOX-catalase (CAT)-AuNPs-gelatin rockets.[39]