We present a combined spectroscopic and computational approach aimed to elucidate the mechanism of formation and activity of etoposide nanoaggregates upon release from dextran-etoposide conjugates. Etoposide is an anticancer drug that inhibits cell growth by blocking Topoisomerase II, the key enzyme involved in re-ligation of the DNA chains during the replication process. In silico and spectroscopic analysis indicate that released etoposide nanoaggregates have a different structure, stability, and bioactivity, which depend on the pH experienced during the release. Molecular dynamics simulation and in silico docking of etoposide dimers suggest that the aggregation phenomena inhibit etoposide bioactivity, yet without drastically preventing Topoisomerase II binding. We correlated the diminished cytotoxic activity exerted by dextran-etoposide conjugates on the A549 lung cancer cells, compared to the free drug, to the formation and stability of drug nanoaggregates.

The development of new antimicrobial therapeutic tools addresses the emergence of multidrug-resistant micro-organisms or clones and the need for more effective antimicrobial strategies. Overcoming the hurdles in providing early diagnosis and intervention on hard-to-reach and/or resting bacteria (i.e. biofilm-embedded cells) represents a challenging task. In this review, we identify a set of organic, inorganic, and hybrid materials that might be used for prevention and control of healthcare-associated infections. We report the current knowledge on nano- and microparticle-based antimicrobial agents and describe the possible mode of their action.

Microbubbles (MB) are small gas-filled colloidal particles (1–8μm) that have specific acoustic properties that make them useful as a contrast agent in ultrasound imaging. The use of the MBs in clinical practice led to the development of more sensitive imaging techniques both in cardiology and radiology, including subharmonic and multipulse imaging, pulse inversion and harmonic power Doppler. Protein-based microbubbles are typically obtained by dispersing of gas phase in the protein solution. The protein deposited/cross-linked on the gas/liquid interface stabilizes the gas core. Innovative applications of protein-MBs prompt the investigation on the properties of MBs obtained using different proteins that are able to confer them specific properties and functionality. Recently, growth factor–releasing scaffolds have been also fabricated by incorporating growth factor–releasing BSA-MBs in the scaffold-manufacturing processes. BSA-MBs have been used as a new porogen to produce BSA-coated cell-friendly surfaces in preserving the bioactivity of loaded growth factor. In a previous work, we have synthesized stable lysozyme microbubbles (Lys-MB) using high intensity ultrasound-induced emulsification of a partly reduced lysozyme in aqueous solutions. Both the hydrophobic nature of the enzyme, to provide foaming properties, and the formation of disulfide bonds are requirements for the formation of stable protein-microbubbles. In the present work a better characterization of Lys-MB obtained was performed demonstrating their biodegradability property. We also present evidence that Lys-MBs can be functionalised by protein, DNA coating and drugs, as carrier for therapeutic applications.