cypate and Breast-Neoplasms

A combination of chemo- and photo-thermal therapy (PTT) has provided a promising efficient approach for cancer therapy. To achieve the superior synergistic chemotherapeutic effect with PTT, the development of a simple theranostic nanoplatform that can provide both cancer imaging and a spatial-temporal synchronism of both therapeutic approaches are highly desired. Our previous study has demonstrated that near-infrared (NIR) light-triggered biodegradable chitosan-based amphiphilic block copolymer micelles (SNSC) containing light-sensitive 2-nitrobenzyl alcohol and NIR dye cypate on the hydrophobic block could be used for fast light-triggered drug release. In this study, we conjugated the SNSC micelles with tumor targeting ligand c(RGDyK) and also encapsulated antitumor drug Paclitaxel (PTX). The results show that c(RGDyK)-modified micelles could enhance the targeting and residence time in tumor site, as well as be capable performing high temperature response for PTT on cancer cells and two-photon photolysis for fast release of anticancer drugs under NIR irradiation. In vitro release profiles show a significant controlled release effort that the release concentration of PTX from micelles was significantly increased with the exposure of NIR light. In vitro and in vivo antitumor studies demonstrate that, compared with chemo or PTT treatment alone, the combined treatment with the local exposure of NIR light exhibited significantly enhanced anti-tumor efficiency. These findings indicate that this system exhibited great potential in tumor-targeting imaging and synchronous chemo- and photo-thermal therapy.

Topics: Animals; Antineoplastic Agents, Phytogenic; Benzyl Alcohols; Breast Neoplasms; Chitosan; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Compounding; Drug Stability; Female; Fluorescent Dyes; Humans; Indoles; Infrared Rays; Integrin alphaVbeta3; MCF-7 Cells; Mice, Nude; Micelles; Paclitaxel; Peptides, Cyclic; Photochemotherapy; Photolysis; Propionates; Time Factors; Tumor Burden; Xenograft Model Antitumor Assays

Matrix metalloproteinase-14 (MMP-14) is involved in cancer invasion, metastasis, and angiogenesis. Therefore, it is considered to be a biomarker for aggressive cancer types, including some of the triple-negative breast cancer. Accurate (i.e., specific) and sensitive detection of MMP-14 can, thus, be important for the early diagnosis of and accurate prognosis for aggressive cancer, including the breast cancer caused by cell line MDA-MB 231. Fluorophore-mediated molecular sensing has been used for detecting biomarkers, for a long time. One way to increase the specificity of the sensing is designing the fluorophore to emit its fluorescence only when it encounters the biomarker of interest. When a fluorophore is placed on the surface of, or very close to a gold nanoparticle (GNP), its fluorescence is quenched. Applying this relationship between the GNP and fluorophore, we have developed a GNP-based, near-infrared fluorescent contrast agent that is highly specific for MMP-14. This agent normally emits only 14-17 % fluorescence of the free fluorophore. When the agent encounters MMP-14, its fluorescence gets fully restored, allowing MMP-14 specific optical signal emission.

Topics: Biomarkers, Tumor; Biosensing Techniques; Breast Neoplasms; Cell Line, Tumor; Contrast Media; Female; Fluorescent Dyes; Gold; Humans; Indoles; Matrix Metalloproteinase 14; Metal Nanoparticles; Molecular Imaging; Propionates; Time Factors