Novel Polymer-metal Hybrid Nanoparticles as Multifunctional SERS Tags in Cancer Detection and Treatment

Abstract

Biocompatible core-shell structured hybrid nanoparticles (NPs), which combine optical properties of a metal nanoshell with the size, shape and attractive properties of a nano-sized polymer core, have emerged as promising nanodevices for high-sensitivity cancer detection and treatment. Among metallic NPs, the bimetallic Au-Ag NP is most attractive due to its high absorption capability and plasmon resonances in the UV-vis-NIR range, which makes it uniquely suitable for many biomedical applications. NPs based on surface enhanced Raman scattering (SERS) are a new class of tags for biodetection including cancer detection. For Au-Ag nanostructures, a signal intensity enhancement factor of 104-106 may be achieved as a result of the signal increase in gaps between the center and sharp tips of a flower-like Au-Ag NP, which is sufficient for obtaining Raman signals large enough to enable single molecule detection. In the present study, two strategies, using either an Au-Ag nanoshell or a nano-sized Au-Ag core, were investigated to create two types of nanodevices for potential cancer detection and treatment applications. The first type was core-shell structured, anti-cancer drug-loaded poly(lactide-co-glycolide) (PLGA)@Ag-Au NPs. Monodispersed, Paclitaxel (PTX)-loaded PLGA NPs were made using a stabilizer-free method, and the PTX encapsulation efficiency approached 95%. A porous Ag nanoshell was then formed in situ on PTX-loaded PLGA NPs through the controlled reduction of AgNO3 by polyvinylpyrrolidone. The NPs thus formed were used to grow Ag-Au nanoshells on the PLGA core in a replacement reaction. In this nanodevice, the bimetallic Ag-Au nanoshell provided SERS enhancement, and in vitro SERS experiments using 4-MBA as the Raman reporter showed that the PLGA@Ag-Au hybrid NPs greatly amplified Raman signals, rendering them as highly desirable SERS optical tags for cancer detection. The antibody anti-HER2 could be conjugated to the nanodevice, enabling it to target HER2-overexpressing SK-BR-3 cancer cells. The hyperthermia effect caused by the Au-Ag shell under NIR-irradiation and drug released from the PLGA core would provide cancer treatment. The second type used highly branched Au-Ag NPs as the core and coated them with a layer of folic acid-chitosan (CS-FA) conjugates. Compared to simple Au or Ag NPs, bimetallic Au-Ag NPs displayed higher SERS. The receptor for FA constituted a useful target for tumor specific detection, which would also facilitate internalization of NPs through cancer cell membrane. Therefore, the nanodevices created were able to target folate receptor over-expressing Hela cells through the folic acid on the nanodevice surface. The hyperthermia effect caused by the Au-Ag core under NIR-irradiation would provide cancer treatment.