Abstract
BackgroundNovel polymeric nanoparticles (NPs) specifically designed for delivering chemotherapeutics in the body and aimed at improving treatment activity and selectivity, cover a very relevant area in the field of nanomedicine.Here, we describe how to build a polymer shell of Hyaluronan (HA) and Polyethyleneimine (PEI) on biodegradable NPs of poly(lactic-co-glycolic) acid (PLGA) through electrostatic interactions and to achieve NPs with unique features of sustained delivery of a docetaxel (DTX) drug cargo as well as improved intracellular uptake.ResultsA stable PEI or HA/PEI shell could be obtained by careful selection of layering conditions. NPs with exquisite stability in salt and protein-rich media, with size and surface charge matching biological requirements for intravenous injection and endowed with sustained DTX release could be obtained. Cytotoxicity, uptake and activity of both PLGA/PEI/HA and PLGA/PEI NPs were evaluated in CD44(+) (A549) and CD44(−) (Calu-3) lung cancer cells. In fact, PEI-coated NPs can be formed after degradation/dissociation of the surface HA because of the excess hyaluronidases overexpressed in tumour interstitium. There was no statistically significant cytotoxic effect of PLGA/PEI/HA and PLGA/PEI NPs in both cell lines, thus suggesting that introduction of PEI in NP shell was not hampered by its intrinsic toxicity. Intracellular trafficking of NPs fluorescently labeled with Rhodamine (RHO) (RHO-PLGA/PEI/HA and RHO-PLGA/PEI NPs) demonstrated an increased time-dependent uptake only for RHO-PLGA/PEI/HA NPs in A549 cells as compared to Calu-3 cells. As expected, RHO-PLGA/PEI NP uptake in A549 cells was comparable to that observed in Calu-3 cells. RHO-PLGA/PEI/HA NPs internalized into A549 cells showed a preferential perinuclear localization. Cytotoxicity data in A549 cells suggested that DTX delivered through PLGA/PEI/HA NPs exerted a more potent antiproliferative activity than free DTX. Furthermore, DTX-PLGA/PEI NPs, as hypothetical result of hyaluronidase-mediated degradation in tumor interstitium, were still able to improve the cytotoxic activity of free DTX.ConclusionsTaken together, results lead us to hypothesize that biodegradable NPs coated with a PEI/HA shell represent a very promising system to treat CD44 overexpressing lung cancer. In principle, this novel nanocarrier can be extended to different single drugs and drug combinations taking advantage of the shell and core properties.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-015-0088-2) contains supplementary material, which is available to authorized users.
Highlights
Novel polymeric nanoparticles (NPs) designed for delivering chemotherapeutics in the body and aimed at improving treatment activity and selectivity, cover a very relevant area in the field of nanomedicine
To improve DTX activity and internalization in airway cancer cells, we tried to engineer biodegradable poly(lactic-co-glycolic) acid (PLGA) NPs with either a PEI coating able to confer a cationic charge to the system or a PEI/HA shell endowed with ability of CD44 receptor targeting
An anionic non endcapped PLGA nanoparticle template entrapping the model anticancer drug DTX was covered with a polycationic layer of PEI (25 kDa, branched)
Summary
Novel polymeric nanoparticles (NPs) designed for delivering chemotherapeutics in the body and aimed at improving treatment activity and selectivity, cover a very relevant area in the field of nanomedicine. Those surface features which affect biological behavior (spatial distribution of drug dose in the body) are controlled, and timing of drug release (temporal control of drug availability to target) is predetermined Due to their well-established biocompatibility and safety profile, nano-oncologicals made of polyesters such as poly(lactic-co-glycolic) acid (PLGA) can be considered one of the most interesting systems for this application and are greatly emerging in the field [2]. A wide array of currently-available materials and possible combinations can be used to fabricate core-shell NPs spanning from tailored amphiphilic polymers, able to form nanoassemblies in aqueous media, to nanostructures where electrostatic or hydrophobic interactions drive shell deposition on a core template [9,11] The latter approach is very attractive since no complicate synthetic steps to attain polymer functionalization are required
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
