Gold nanostars conjugated with dimethylmethylene blue for the diagnosis of overexpressed proteins in tumors

• Grant number: 25/12197-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2025
• End date: July 31, 2027
• Field of knowledge: Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
• Principal Investigator: Sabrina Aléssio Camacho
• Grantee: Melissa Nishida Hirano
• Host Institution: Faculdade de Ciências e Letras (FCL-ASSIS). Universidade Estadual Paulista (UNESP). Campus de Assis. Assis , SP, Brazil
• Associated research grant: 23/17867-9 - Multifunctional approach of gold nanostructures coated with silica: combining the diagnosis of circulating cancer cells with the tumor phototherapy, AP.JP

Abstract

Breast cancer and colorectal cancer are among the most prevalent cancers, accounting for approximately 2.25 and 1.93 million cases, respectively, in the year 2020. These high incidence levels are reflected in mortality rates, with around 680,000 deaths caused by breast cancer and 930,000 by colorectal cancer.¹ The most commonly used detection methods have the drawback of requiring the injection of markers into patients, either intravenously or into tissues, in addition to the difficulty of imaging deeper cancerous cells in diagnostic imaging techniques.²,³ Furthermore, traditional cancer treatment strategies such as surgery, radiotherapy, and chemotherapy, though widely used, still suffer from severe side effects and limited therapeutic efficacy.¿,¿,¿ In this context, multifunctional nanostructures, such as those formed by gold nanoparticles (AuNPs), have attracted extensive interest for their potential in both cancer diagnosis and treatment. In particular, gold nanostars (AuNSs) stand out as multifunctional agents due to their high biocompatibility and localized surface plasmon resonance, which can be tuned to the near-infrared (NIR) region-a promising range for applications such as biosensors.¿ Additionally, conjugation with fluorescent molecules, such as photosensitizers (PS), enhances the development of nanoparticles for diagnostic purposes. The photosensitizer dimethylmethylene blue (DMMB) is a molecule from the phenothiazinium family that presents an absorbance spectrum within the therapeutic window, in the near-infrared region. In this master's project 1, we will develop multifunctional nanostructures capable of diagnosing traces of overexpressed proteins in tumor cells, aligning with the proposed timeline for the 1st, 2nd, and 5th years of the JP Project. The application of these nanostructures in cancer treatment will be addressed in the direct PhD project. The nanostructures will be composed of gold nanostars coated with silica (AuNSs@SiO¿), conjugated with the PS dimethylmethylene blue (DMMB), coated with a second silica shell, and functionalized with specific biomolecules such as antibodies targeting proteins overexpressed in breast and colorectal cancers (e.g., anti-p53, anti-SAE1, or anti-STIP1), yielding AuNS@SiO¿-DMMB-SiO¿-Ab. The resonance between the plasmon of the AuNS@SiO¿ and the excitation/emission of the PS will promote fluorescence amplification (SHINEF - shell-isolated nanoparticles-enhanced fluorescence) for diagnostic purposes, and a synergy between photothermal therapy (PTT) and photodynamic therapy (PDT) for treatment. These nanostructures will be used in the construction of diagnostic platforms based on the SHINEF effect, resulting from the PS confined between the silica shells, and applied to detect trace levels of isolated proteins (~pg/mL) that are overexpressed in certain types of cancer, such as breast and colorectal cancers. (AU)