Towards theranostic multicompartment microcapsules: in-situ diagnostics and laser-induced treatment

Abstract

Paving the way towards the application of polyelectrolyte multilayer capsules in theranostics, we describe diagnostic multi-functionality and drug delivery using multicompartment polymeric capsules which represent the next generation of drug delivery carriers. Their versatility is particularly important for potential applications in the area of theranostics wherein the carriers are endowed with the functionality for both diagnostics and therapy. Responsiveness towards external stimuli is attractive for providing controlled and on-demand release of encapsulated materials. An overview of external stimuli is presented with an emphasis on light as a physical stimulus which has been widely used for activation of microcapsules and release of their contents. In this article we also describe existing and new approaches to build multicompartment microcapsules as well as means available to achieve controlled and triggered release from their subcompartments, with a focus on applications in theranostics. Outlook for future directions in the area are highlighted.

Keywords: capsules; laser; multicompartment; nanoplasmonics.; stimuli; theranostics.

Figure 1

Overview and the road-map for future directions of multicompartment microcapsules.Four different approaches are identified in the schematics: a) concentric, b) pericentric, c) innercentric, and d) acentric. The structure in the middle incorporates all four approaches. The corresponding confocal microscope images of the first steps in each direction are also presented. Scale bars correspond to 2 mm. Reproduced by permission of Wiley-VHC.

Figure 2

Fluorescence CLSM images showing an overview of a-f) half covered (4.8 μm SiO₂)@QDs (quantum dots) and g-l) 2/3 covered (SiO₂)@QDs. Dotted lines represent the centre line, while bold lines show the termination of particle modification. Images a) and g) show top view, while c-f) and i-l) depict side view of protruding SiO₂ particles into FITC labeled (HA/PLL)₁₂ films with AuNP concentration of a-f) 0 μl and g-l) 300 μL. Arrows in a) and g) point to location of particles; insets in a) and g) show magnification of the transmission images of protruding (SiO₂) particles into (HA/PLL)₁₂ films. Arrows in b) and h) indicate the (HA/PLL)₁₂ film height. Scale bars correspond to 5 μm. Reproduced by permission of Wiley-VHC.

Figure 3

Schematics showing various methods of release. The three main categories: physical, biological and chemical, are further sub-divided and are shown with specific methods of release. Reproduced by permission of The Royal Society of Chemistry.

Figure 4

a) Evolution of the enzymatic reaction inside porous microparticles. b-d) Confocal transmission (middle row) and fluorescence (bottom row) images of microparticles after 1 min (b), 10 min (c), and 15 min (d) of ultrasonication and addition of H₂O₂. The insets show fluorescence profiles drawn across the same microcontainer (the red lines in the bottom row). The red profiles in the insets corresponds to emission 1 min after sonication, the yellow and white profiles to emission 10 and 15 min after sonication, respectively. Reproduced by permission of Wiley-VHC.

Figure 5

Hierarchy of multicompartment particles for conversion of reactants to products. Reproduced by permission from . Copyright (2011) American Chemical Society.

Figure 6

Confocal microscope images demonstrating remote release of encapsulated rhodamine-labeled PSS polymers from a polyelectrolyte multilayer capsule containing gold sulfide core/gold shell nanoparticles in its walls. Fluorescence intensity profiles along the line through the capsule show that it is filled with fluorescent polymers before (a) and empty after (b) laser illumination. After the release of encapsulated polymers, the leftover fluorescent intensity is observed only in the walls of the capsule, (b). Insets show black and white transmission microscope images of the same capsule. Incident intensity of laser diode operating at 830 nm was set at 50 mW. Reproduced with permission from . Copyright (2005) American Chemical Society.

Figure 7

Schematics of implementation of theranostic multicompartment capsules: diagnostics is achieved by monitoring pH, glucose, lactose, etc., while therapy is attained by release of encapsulated drugs/medicine.