Entrapment of hydrophobic drugs in nanoparticle monolayers with efficient release into cancer cells

Abstract

Gold nanoparticles functionalized with water-soluble zwitterionic ligands form kinetically stable complexes with hydrophobic drugs and dyes. These drugs and dyes are efficiently released into cells, as demonstrated through fluorescence microscopy and cytotoxicity assays. Significantly, there is little or no cellular uptake of particle, making these low toxicity particles promising for delivery applications.

Figure 1

a) Delivery of payload to cell through monolayer-membrane interactions. b) Structure of particles and guest compounds: Bodipy, TAF, and LAP, the number of encapsulated guests per particle, and logP of the guests. c) Release of Bodipy from AuNPZwit-Bodipy in DCM-aqueous solution two-phase systems (λ_ex = 499 nm, λ_em = 517 nm) d) PL intensity AuNPZwit-Bodipy in cell culture medium and 100 % serum, indicating little or no release relative to AuNPZwit-Bodipy in PBS after NaCN-induced release of guest molecules ((λ_ex = 499 nm, λ_em = 510 nm).

Figure 2

CLSM images of MCF-7 cell treated with AuNPZwit-Bodipy for 2h: a) green channel b) bright field, and c) overlap. TEM images of fixed cell treated with d) AuNPZwit-Bodipy and e) AuNPTTMA as a positive control, Endosomally trapped AuNPs are marked by arrow. (f) ICP-MS measurement. (200,000 cells/well), indicating low cellular uptake of AuNPZwit (31 ng/well after 4 h)

Figure 3

Cytotoxicity of AuNPZwit complexes measured by Alamar blue assay after 24h incubation with MCF-7 cells. IC₅₀ of AuNP (NP), equivalent drugs (Drug), and free drugs are shown in table.