The engineering of delivery systems for drugs and contrasting labels ensuring the simultaneous imaging and treatment of malignant tumors is an important hurdle in developing new tools for cancer therapy and diagnosis. Polyelectrolyte microcapsules (MCs), formed by nanosized interpolymer complexes, represent a promising platform for the designing of multipurpose agents, functionalized with various components, including high- and low-molecular-weight substances, metal nanoparticles, and organic fluorescent dyes. Here, we have developed size-homogenous MCs with different structures (core/shell and shell types) and microbeads containing doxorubicin (DOX) as a model anticancer drug, and fluorescent semiconductor nanocrystals (quantum dots, QDs) as fluorescent nanolabels. In this study, we suggest approaches to the encapsulation of DOX at different stages of the MC synthesis and describe the optimal conditions for the optical encoding of MCs with water-soluble QDs. The results of primary characterization of the designed microcarriers, including particle analysis, the efficacy of DOX and QDs encapsulation, and the drug release kinetics are reported. The polyelectrolyte MCs developed here ensure a modified (prolonged) release of DOX, under conditions close to normal and tumor tissues; they possess a bright fluorescence that paves the way to their exploitation for the delivery of antitumor drugs and fluorescence imaging.
Fluorescent semiconductor nanocrystals or quantum dots (QDs) are characterized by unique optical properties, including a high photostability, wide absorption spectrum, and narrow, symmetric fluorescence spectrum. This makes them attractive fluorescent nanolabels for the optical encoding of microcarriers intended for targeted drug delivery, diagnosis, and imaging of transport processes on the body, cellular, and subcellular levels. Incorporation of QDs into carriers in the form of polyelectrolyte microcapsules through layer-by-layer adsorption of oppositely charged polyelectrolyte polymers yields microcapsules with a bright fluorescence signal and adaptable size, structure, and surface characteristics without using organic solvents. The easily modifiable surface of the microcapsules allows for its subsequent functionalization with capture molecules, such as antibodies, which ensures specific and selective interaction with cells, including tumor cells, with the use of the bioconjugation technique developed here. We obtained stable water-soluble nanolabels based on QDs whose surface was modified with polyethylene glycol (PEG) derivatives and determined their colloidal and optical characteristics. The obtained nanocrystals were used to encode polyelectrolyte microcapsules optically. The microcapsule surface was modified with humanized monoclonal antibodies (Abs) recognizing a cancer marker, epidermal growth factor receptor (EGFR). The possibility of effective, specific, and selective delivery of the microcapsules to tumor cells expressing EGFR has been demonstrated. The results show that the QD-encoded polyelectrolyte microcapsules functionalized with monoclonal Abs against EGFR can be used for targeted imaging and diagnosis.
The development of delivery systems providing prolonged release of antitumor drugs represents one of the challenges in designing and optimization of novel tools for cancer therapy. The employment of spherical inorganic microparticles, in particular, calcium carbonate vaterite microspheres, as microcarriers appears promising because of their porous, matrix structure, biocompatibility, and biodegradability. Here, we summarize the results of the development of the approaches to synthesis of calcium carbonate vaterite microspheres with narrowed size distribution and microencapsulation of low-molecular-weight anticancer drugs, such as doxorubicin hydrochloride into obtained microspheres. Supplementing the reaction mixture with a thickener defines fabrication of homogeneous vaterite microparticles with a spherical shape and an average size of 2 to 3 μm. Synthesised microspheres ensure prolonged release of doxorubicin at physiological pH values and can be used as a delivery system and as a structural component for development of a theranostic platform for tumour treatment and diagnosis.
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