The paradigm of drug delivery via particulate formulations is one of the leading ideas that enable overcoming limitations of traditional chemotherapeutic agents. The trend toward more complex multifunctional drug carriers is well-traced in the literature. Nowadays, the prospectiveness of stimuli-responsive systems capable of controlled cargo release in the lesion nidus is widely accepted. Both endogenous and exogenous stimuli are employed for this purpose; however, endogenous pH is the most common trigger. Unfortunately, scientists encounter multiple challenges on the way to the implementation of this idea related to the vehicles’ accumulation in off-target tissues, their immunogenicity, the complexity of drug delivery to intracellular targets, and finally, the difficulties in the fabrication of carriers matching all imposed requirements. Here, we discuss fundamental strategies for pH-responsive drug delivery, as well as limitations related to such carriers’ application, and reveal the main problems, weaknesses, and reasons for poor clinical results. Moreover, we attempted to formulate the profiles of an “ideal” drug carrier in the frame of different strategies drawing on the example of metal-comprising materials and considered recently published studies through the lens of these profiles. We believe that this approach will facilitate the formulation of the main challenges facing researchers and the identification of the most promising trends in technology development.

Originally regarded as auxiliary additives, nanoparticles have become important constituents of polyelectrolyte multilayers. They represent the key components to enhance mechanical properties, enable activation by laser light or ultrasound, construct anisotropic and multicompartment structures, and facilitate the development of novel sensors and movable particles. Here, we discuss an increasingly important role of inorganic nanoparticles in the layer-by-layer assembly—effectively leading to the construction of the so-called hybrid coatings. The principles of assembly are discussed together with the properties of nanoparticles and layer-by-layer polymeric assembly essential in building hybrid coatings. Applications and emerging trends in development of such novel materials are also identified.

We have designed multifunctional silver alginate hydrogel microcontainers referred to as loaded microcapsules with different sizes by assembling them via a template assisted approach using natural, highly porous calcium carbonate cores. Sodium alginate was immobilized into the pores of calcium carbonate particles of different sizes followed by cross-linking via addition of silver ions, which had a dual purpose: on one hand, the were used as a cross-linking agent, albeit in the monovalent form, while on the other hand they have led to formation of silver nanoparticles. Monovalent silver ions, an unusual cross-linking agent, improve the sensitivity to ultrasound, lead to homogeneous distribution of silver nanoparticles. Silver nanoparticles appeared on the shell of the alginate microcapsules in the twin-structure as determined by transmission electron microscopy. Remote release of a payload from alginate containers by ultrasound was found to strongly depend on the particle size. The possibility to use such particles as a platform for label-free molecule detection based on the surface enhanced Raman scattering was demonstrated. Cytotoxicity and cell uptake studies conducted in this work have revealed that microcontainers exhibit nonessential level of toxicity with an efficient uptake of cells. The above-described functionalities constitute building blocks of a theranostic system, where detection and remote release can be achieved with the same carrier.

Multifunctional silver alginate hydrogel microspheres are assembled via a template assisted approach using calcium carbonate cores. Sodium alginate is immobilized into the highly porous structure of calcium carbonate microspheres followed by cross-linking in the presence of silver ions. The simultaneous processes of the growth of silver nanoparticles in the alginate matrix and the removal of the calcium carbonate template are triggered by ascorbic acid. The abundance of silver nanoparticles and their interparticular junctions in the alginate network allow for the detection of solutes using Raman spectroscopy using the surface of the plasmonic microspheres. Rhodamine B was used to illustrate the potential applications of such multifunctional plasmonic alginate hydrogel microspheres for sensing at low concentrations. A proof of principle for using such particles for the quick identification of microorganisms is then demonstrated using the Escherichia coli bacterium.