Degradable silica nanoparticles: inclusion of sulphide bridges as a strategy for advanced applications in nanomedicine

Author(s)

Juliana Tosta Theodoro Carvalho

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2024-02-28

Examining board members

Mateus Borba Cardoso; Watson Loh; Aline Ribeiro Passos

• Advisor: Mateus Borba Cardoso

Abstract

Precision medicine aims to enhance traditional theragnostic methods. However, the transition from laboratory research to practical applications is challenged by limited understanding of interactions between nanoparticles (NPs) and biological systems. Issues of colloidal stability in biological environments, biocompatibility, and post-administration integrity of NPs need to be addressed. The formation of the protein corona (PC), where proteins spontaneously adsorb to the surface of NPs upon contact with biological fluids, is a critical phenomenon that can determine the success or failure of NPs. Undesirable scenarios such as bioaccumulation and lack of selective biodistribution must also be considered. In this context, NPs capable of being biodegradable emerge as a potential platform to avoid potential bioaccumulation and target action in specific biological environments. The tumor microenvironment (TME), where cancer cells proliferate, presents a unique chemical composition with the overexpression of reducing agents that play a role in the design of NPs responsive to redox stimuli. However, factors such as the prior formation of the PC and surface functionalization can be aggravating factors that compromise the degradability of NPs and may lead to early clearance. This work sought to include disulfide bridges in silica NPs as a strategy to enable selective degradation of NPs. Degradation was monitored through imaging and spectroscopy techniques, revealing a heterogeneous degradation profile for degradable NPs, even after surface functionalization with PEG groups. Furthermore, interactions of human serum albumin (HSA) in reducing environments and in the PC were analyzed by circular dichroism (CD) and FTIR, respectively. CD results show that GSH has a low capacity to induce conformational changes in HSA, while synthetic reducing agents, such as DTT, cause severe alterations to the protein. Additionally, FTIR results show that conformational changes in HSA occur when the PC forms on the surface of NPs, which may induce undesirable subsequent responses by the immune system. In summary, the results obtained open new perspectives for the design of NPs intended for precision medicine, emphasizing the importance of considering factors such as the formation of the PC and the response to reducing agents, especially in applications within the TME. These findings aim to highlight that the PC should not be overlooked in the context of nanomaterials whose primary mechanism is to interact with endogenous stimuli (AU)

• FAPESP's process: 21/12225-3 - Silica nanoparticles degradation in physiologic media: morphology, colloidal stability and surface interactions evolution
• Grantee: Juliana Tosta Theodoro Carvalho
• Support Opportunities: Scholarships in Brazil - Master