Bio-inspired protein–gold nanoconstruct with core–void–shell structure: beyond a chemo drug carrier

Abstract

Chemotherapy has been widely used in clinical practice for cancer treatment. A major challenge for a successful chemotherapy is to potentiate the anticancer activity, whilst reducing the severe side effects. In this context, we design a bio-inspired protein-gold nanoconstruct (denoted as AFt-Au hereafter) with a core-void-shell structure which exhibits a high selectivity towards carcinoma cells. Anticancer drug 5-fluorouracil (5-FU) can be sequestered into the void space of the construct to produce an integrated nanoscale hybrid AFt-AuFU that exhibits an increased cellular uptake of 5-FU. More importantly, AFt-Au, serving as a bio-nano-chemosensitizer, renders carcinoma cells more susceptible to 5-FU by cell-cycle regulation, and thus, leads to a dramatic decrease of the IC 50 value (i.e. the drug concentration required to kill 50% of the cell population) of 5-FU in HepG2 cells from 138.3 mM to 9.2 mM. Besides HepG2 cells, a remarkably enhanced anticancer efficacy and potentially reduced side effects are also achieved in other cell lines. Our further work reveals that the drug 5-FU is internalized into cells with AFt-Au primarily via receptor-mediated endocytosis (RME). After internalization, AFt-AuFU colocalizes with lysosomes which trigger the release of 5-FU under acidic conditions. Overall, our approach provides a novel procedure in nanoscience that promises an optimal chemotherapeutic outcome.Scheme 1 Design and construction of the AFt-AuFU nanoconstruct. AFt-Au was prepared by reducing AuCl 4À ions with NaBH 4 in the cavity of apoferritin. 5-FU was sequestered into the resulting void space of the AFt-Au complex by passive diffusion through the molecular channels in the apoferritin shell to produce a drug-loaded hybrid nanoconstruct (AFt-AuFU).

Cytotoxic Effects of Thiazolo[3,2-C]Pyrimidines Against Mcf-7 And Hepg2/C3a Carcinoma Cell Lines

“…They corresponded to 99μM, 94μM and 92μM, respectively (Table 4). Calculated IC 50 value of 5-FU (85 μM) complies with its other published literature data against human breast cancer cell lines (MCF-7) [27][28][29][30][31][32]. Twelve other derivatives (4a-c, 5a-c, 5e, 5g-i, 5k) showed moderate to weak cytotoxic activities (53-87% cell viability) (Table 1) and so, their IC 50 values were obtained higher than 100μM which were not very significant results for this test.…”

Protein cage nanostructure as drug delivery system: magnifying glass on apoferritin

“…The cytostatic drug 5-fluorouracil (5-FU), being characterized by a low molecular weight, rapidly leak from the APO cavity; thus to better stabilize the encapsulation, [82] proposed a simultaneous loading with gold nanoparticles (AU-NPs, 3nm of diameter) known for their optical and photothermal proprieties. 5-FU enters trough hydrophilic protein pores and once into the protein core binds AU-NPs via electrostatic interaction.…”

Synthesis of bio-degradable poly(2-hydroxyethyl methacrylate) using natural deep eutectic solvents for sustainable cancer drug delivery

“…Moreover, this carrier occurred in a sustained release manner and had the controlled release behavior. This could confirm that the 5-FU loaded NADESpoly(HEMA) carrier has penetrated the cell membrane and internalized into the cell nucleus [45].…”