Near-infrared light-responsive core-shell nanogels for targeted drug delivery

Abstract

A near-infrared light-responsive drug delivery platform based on Au-Ag nanorods (Au-Ag NRs) coated with DNA cross-linked polymeric shells was constructed. DNA complementarity has been applied to develop a polyacrylamide-based sol-gel transition system to encapsulate anticancer drugs into the gel scaffold. The Au-Ag NR-based nanogels can also be readily functionalized with targeting moieties, such as aptamers, for specific recognition of tumor cells. When exposed to NIR irradiation, the photothermal effect of the Au-Ag NRs leads to a rapid rise in the temperature of the surrounding gel, resulting in the fast release of the encapsulated payload with high controllability. In vitro study confirmed that aptamer-functionalized nanogels can be used as drug carriers for targeted drug delivery with remote control capability by NIR light with high spatial/temporal resolution.

Figure 1

(A) A schematic diagram illustrating the formation of an aptamer-functionalized core-shell nanogel. B) The DNA sequences and linkages in the nanogel (not to scale).

Figure 2

(A) Transmission electron microscopy (TEM) images and (B) UV-visible spectra of (a) Au-Ag NRs, (b) silica-coated Au-Ag NRs, and (c) NR-based nanogels (the inserted image is a single nanogel). Scale bars: (a) 100 nm, (b) 500 nm, (c) 1 µm.

Figure 3

Controlled release of the entrapped fluorescein from the core-shell nanogels (10 nM) by visible and NIR light irradiations.

Figure 4

Flow cytometric assay to monitor the binding of fluorescein (FAM)-labeled sgc8c–nanogel (sgc8c-NG) conjugates (2 nM) to (A) CCRF-CEM (target) cells and (B) Ramos (control) cells at 4 °C for 1 h. The red curve represents the cells only; the green curves represent the background binding of nanogel tethered with FAM-labeled random DNA library (lib-NG); and the light blue and dark blue curves represent the FAM-labeled sgc8c-NG conjugates incubated with CEM and Ramos cells, respectively.

Figure 5

Cytotoxicity assays of (A) CCRF-CEM (target) cells and (B) Ramos (control) cells in the absence of nanogels (a), and those incubated with (b) Dox (0.75 µM), (c) sgc8c–NGs (2 nM), (d) Dox-loaded lib-NGs (2 nM), and (e) Dox-loaded sgc8c–NGs (2 nM) in culture medium without FBS at 37 °C, 5% CO₂ for 2h. Cells were exposed to a near infrared laser at 808 nm (600 mW) for 0, 5, and 10 min, respectively (blue, red and green). After treatment, cells were subsequently grown in fresh medium (10% FBS) for 48 h. The cytotoxicity was then measured by an MTS assay.