Smart dendrimer-based nanogel for enhancing 5-fluorouracil loading efficiency against MCF7 cancer cell growth

Abstract

Nano-carriers are not only evaluated as a novel kind of drug delivery, but also expected to bypass the critical bottleneck of conventional cancer chemotherapeutics. Among them, thermo-sensitive nanogel draws much attention due to its efficacy in the loading and release of hydrophobic drugs. In the study, we developed a promising thermosensitive polymer-grafted dendrimer to enhance drug-loading efficiency, which was prepared from conjugation of thermo-sensitive carboxylic-terminated poly(N-isopropylacrylamide) polymer (PNIPAM) with polyamidoamine (PAMAM) dendrimer (G3.0). The obtained copolymer structure and molecular weight were confirmed by proton nuclear magnetic resonance (¹H NMR) and gel permeation chromatography (GPC), respectively. Morphology of the nanocarrier was observed around 120–150 nm by transmission electron microscopy (TEM) and 200 nm by dynamic light scattering (DLS). The nanocarrier exhibited the higher drug loading (DL = 7.79%) and entrapment efficiency (EE = 42.25%) of 5-FU compared to PAMAM dendrimer G3.0 (DL = 2.25% and EE = 11.52%). In-vitro test, the 5-FU-loaded in PAMAM G3.0–PNIPAM could release approximately 40% of the encapsulated drug at pH = 7.4 after 5 days tracking, while the cumulative anticancer drugs achieved nearly two-fold increase (around 75%) at pH 5.5 during the same time. Moreover, the cytotoxicity assay results also indicated that the drug-loaded nanocarrier exhibited a significant growth inhibition of the MCF-7 cancer cell. The obtained resulted possibly offered a great potential of the nanocarrier which may be utilized in delivering other anticancer drugs or dual drugs for chemotherapy in future.