Tracing the Therapeutic Process of Targeted Aptamer/Drug Conjugate on Cancer Cells by Surface-Enhanced Raman Scattering Spectroscopy

Abstract

Targeted delivery of chemotherapeutic agents to pathology areas can improve drug efficiency and reduce serious side effects on normal regions. However, their treatment mechanism on cells or cell nuclei is still mysterious due to the lack of in situ characterization methods. In this paper, the specific diagnosis and treatment processes of a targeted antitumor agent (doxorubicin, Dox) functionalized aptamer complex (TLS11a-GC-Dox) toward HepG2 cells, a human hepatocellular carcinoma cell line, were tracked in real time by the surface-enhanced Raman scattering (SERS) spectroscopic technique and dark-field imaging with the assistance of gold nanorod-based nuclear targeted probes, which possess remarkable SERS enhancement ability, specific targeting, and excellent biological compatibility. This is the first time to explore the acting mechanism of an aptamer-based targeted drug on cell nucleus based on the spectral information on components inside the cell nucleus. The results demonstrate that this aptamer/drug conjugate has targeting and sustained-release actions and its therapeutic effect is achieved by the gradual damage of relevant proteins and DNA in nuclei. Better understanding of the mechanism of aptamer-drug conjugates acting on cancer cells is conductive to increasing cancer therapy efficiency and is also helpful for the design of highly effective drug delivery methods.

In situ and ex situ surface‐enhanced Raman spectroscopy (SERS) analysis of cell mitochondria

“…The mitochondrial targeting nanoprobes were obtained by modifying AuNRs with methoxypoly (ethylene glycol)‐thiol (PEG), RGD (CGGGPKKKRKGC), and mitochondrial targeting peptides (MLS, MLALLGWWWFFSRKKC) step by step according to our previously published methods . The successful conjunctions of PEG, RGD, and MLS were evaluated by ultraviolet‐visible (Uv‐vis) spectroscopy (Ocean Optics, USB4000) and the zeta potential (Malvern Zetasizer Nano ZS).…”

Programmable and Multifunctional DNA‐Based Materials for Biomedical Applications

“…The aptamer sgc8c has also been conjugated with anticancer drug 5‐FU through photocleavable nitrobenzene derivative linker, and the efficient photocontrollable release of the 5‐FU moiety was achieved in responsive of UV irradiation at 365 nm (Figure c) . In another work, the DOX‐functionalized aptamer complex TLS11a‐GC‐DOX could effectively lead to HepG2 cells apoptosis by gradually damaging of relevant proteins and DNA in nuclei . The aforementioned examples demonstrated drug–aptamer conjugate with controlled chemotherapy release performed by using both internal and external stimuli.…”

Raman Scattering: From Structural Biology to Medical Applications

“…RS applications for cancer are not limited to diagnostic purposes. This method could also provide important information when used for monitoring cancer cell structure and physiology during treatment in experimental models [26][27][28]. [197] with permission by Creative Commons License.…”

“…RS complementarily applied with SHG, UV-TPEF, and other imaging techniques is a promising approach for fast and accurate non-invasive cancer diagnostics [23,25]. In addition, RS can be a useful tool for monitoring cancer cell response for therapy [26][27][28].…”