Core–Shell Nanoparticles as an Efficient Sustainedand Triggered Drug-DeliverySystem

摘要

One of the challenges in designing a successful drug-delivery vehicle is the control over drug release. Toward this, a number of multifunctional nanoparticles with multiple triggers and complex chemistries have been developed. To achieve an efficient and maximum therapeutic effect, a trigger dependent drug-delivery system with sustained release is desirable. In this paper, we report the use of a combination of thermoresponsive gold core and polymeric shell nanoparticles that can provide a sustained, triggered release of doxorubicin, making the system more efficient compared to individual nanoparticles. The selection of the system was dependent on the best trigger applicable in biological systems and a component responsive to that trigger. Because of the best tissue penetration depth observed for radiofrequency (rf), we chose rf as a trigger. Whereas the gold nanoparticles (AuNPs) provided hyperthermia trigger on exposure to rf fields, the thermoresponsiveness was endowed by poly(N-isopropylacrylamide) (pNIPAm)-based polymer shells. AuNPs with three different compositions of shells, only pNIPAmand p(NIPAm-co-NIPMAm) with the ratio of NIPAm/N-(isopropylmethacrylamide) (NIPMAm) 1:1 (pNIPMAm50) and 1:3 (pNIPMAm75), were synthesized. We observed thatthe polymer coating on the AuNPs did not affect the heating efficiencyof AuNPs by rf and exhibited a temperature-dependent release of thechemotherapeutic drug, doxorubicin. The nanoparticles were biocompatible,stable in biologically relevant media, and were able to show a burstas well as a sustained release, which was rf-dependent. Interestingly,we observed that when HeLa cells were treated with doxorubicin-loadedgold core–polymeric shell NPs and exposed to rf for varyingtimes, the mixture of the two polymeric shell nanoparticles inducedmore cell death as compared to the cells treated with single nanoparticles,suggesting that such multi-nanoparticle systems can be more efficaciousdelivery systems instead of a single multicomponent system.