Enhancement Of Gold Nanometer In Tumor Photodynamic Detection And Treatment

Photodynamic therapy (PDT) has been developed as a new treatment modality for cancers and has been approved for clinical use for several types of cancer in many countries. Under irradiation of light of appropriate wavelengths, the PS molecules that have accumulated in the tumor would exhibit two main mechanisms of deexcitation of their electronically excited state:emission of fluorescence and intersystem crossing that leads to production of singlet oxygen (1O2), which may destroy cancer cells by indiscriminate oxidation. With these characteristics, PDT can be applied for both cancer detection and therapy. In the course of development of PDT, the improvement of the PS is always the core issue.With the rapid development of nanotechnology, the use of nanoparticles as vehicles for drug delivery to tumors has been conducted, relying on the fact that nanoparticles with the size around tens of nm can preferably accumulate in tumors by the effect of enhanced permeability and retention (EPR), whereas the drug molecules themselves are too small to accumulate in tumors effectively by this effect. Among various nanoparticles, such as liposomal vesicles, quantum dots (QDs), nanotubes and gold nanoparticles, the latter have attracted much attention, because of their chemical inertness, excellent optical properties and minimum biological toxicity. Among gold nanoparticles, gold nanorods (AuNRs) are particularly attractive, due to their flexible structure owing to the synthetic control of their size and aspect ratio. AuNRs have two surface plasmon resonances (transverse and longitudinal, TSPR and LSPR) which are much stronger than in gold spheres. The strong SPRs make AuNRs suitable for enhancing the fluorescence and Raman signals of55surface adhered molecules. The test of gold nanoparticles carrying PSs has been reported, as the gold nanoparticles with a diameter of about5nm can adsorb silica phthalocyanines (Pc4) on their surfaces with a loading rate of about30Pc4molecules per particle and such loaded Pc4can be detected in the60tumor. However, such Pc4loading was not encouraging for photodynamic detection because the fluorescence of these surface-attached Pc4was partially quenched as compared to that of free Pc4. The relatively long binding distance in the case of Pc4and the weak SPRs on those gold spheres are probably the reasons for the fluorescence quenching. The binding distance between the fluorescent molecules and the metal was reported as a key factor. Generally, the strong surface plasmons on metals should enhance Raman and fluorescence of the adsorbed molecules if they are close to the surface, within a range of a few nanometres. Therefore, AuNRs are probably more suitable candidate to load PSs and enhance the PS fluorescence for facilitating PDT detection of cancers. The size of AuNRs is usually in the range of30-50nm, which fits well the requirement of the tumor accumulation by the EPR effect. In addition, the water-soluble AuNRs are commonly coated with cetyltrimethylammonium bromide (CTAB) possessing positive charges on their surfaces, so that the negatively charged PSs can be easily bound on the AuNRs surface by electrostatic attraction and the fluorescence of these PSs could be expected to be enhanced.In this work, the commonly used chlorin e6(Ce6) was selected as the PS to connect on the surface of AuNRs, because Ce6is an effective PS and it carries negative charges of COO’on its side chains. We found that the conjugates of AuNRs-Ce6can enhance strongly, by factor of3, the fluorescence of Ce6and deliver the Ce6more efficiently into cancer cells and thus increase the PDT killing efficiency.