Over the last few decades, nanocarriers for drug delivery have emerged as powerful tools with unquestionable potential to improve the therapeutic efficacy of anticancer drugs. Many colloidal drug delivery systems are underdevelopment to ameliorate the site specificity of drug action and reduce the systemic side effects. By virtue of their small size they can be injected intravenously and disposed into the target tissues where they release the drug. Nanocarriers interact massively with the surrounding environment, namely, endothelium vessels as well as cells and blood proteins. Consequently, they are rapidly removed from the circulation mostly by the mononuclear phagocyte system. In order to endow nanosystems with long circulation properties, new technologies aimed at the surface modification of their physicochemical features have been developed. In particular, stealth nanocarriers can be obtained by polymeric coating. In this paper, the basic concept underlining the “stealth” properties of drug nanocarriers, the parameters influencing the polymer coating performance in terms of opsonins/macrophages interaction with the colloid surface, the most commonly used materials for the coating process and the outcomes of this peculiar procedure are thoroughly discussed.

Surface decoration of gold nanoparticles with thermoresponsive polymers endows a temperature tunable colloidal system switchable for enhanced intracellular up-take. Gold nanoparticles (AuNP, 18 ± 11 nm-diameter) produced by laser ablation synthesis in liquid solution were surface coated with thermoresponsive thiol terminated poly-N-isopropylacrylamide-co-acrylamide co-polymer possessing a lower critical solution temperature (LCST) at 37 °C. Under selected conditions about 3800 polymer chains were conjugated per particle. The polymer coated nanoparticles were found to display thermosensitive properties, as in solution they exhibited reversible aggregation/deaggregation above and below the LCST, respectively. Cell culture studies showed that the polymer decorated AuNP were located into human breast adenocarcinoma MCF7 cells treated at 40 °C (12000 AuNP/cell) with more than 80-fold greater up-take compared to cells treated at 34 °C with the same particles (140 AuN/cell). This difference is attributable to a ‘switching’ of the polymer coating to a globule state at 37 °C and an increased hydrophobicity of the particles with a simultaneous loss of the ‘stealth’ properties of the polymer coating. By contrast, cell up-take of uncoated AuNP (about 6000 AuNP/cell) did not depend on the incubation temperature. These data show that good control of the AuNP cell up-take can be obtained with the new polymer-gold nanoconjugates, and suggest that these systems might find use for targeting cellsin vitro by a small temperature change or in vivo in body sites, such as inflamed or tumour tissues, where a temperature variation is already present.