Nanopartículas para transportar moléculas bioativas direcionadas de forma seletiva para combater infeções bacterianas

The primary SCIENTIFIC AIM of this project is to enhance the penetration of Nucleic acid mimics (NAMs) and microalgae-derived peptides (MDPs) across the bacterial envelope of gram-positive and gram-negative bacteria, thereby advancing their potential as innovative and efficacious antibacterial nanomedicines. To achieve this, we propose nanotech-double functionalized nanoparticles (NPs) for transporting NAMs or MDP sto mitigate bacterial infections and combat AMR. Given the barriers hindering the development of antibacterial strategies, nanotechnology emerges as a promising approach to surmount these challenges and facilitate the creation of innovative therapies. Consequently, this endeavor centers on encapsulating NAMs or MDP within poly(lactic-co-glycolic acid) (PLGA) NPs. The encapsulation of these bioactive molecules within NPs featuring modified surface is envisioned to augment their specificity and intracellular uptake within bacteria. Initially conceived for intravenous administration, this nanostrategy holds promise for potential expansion to other routes of administration, such as oral and topical. Besides, the versatility of this approach suggests its applicability in treating various bacterial infections caused by other pathogens, leveraging different NAMs, PDM, and phage proteins tailored to specific bacterial strains. The overarching goal will be attained through the pursuit of five specific objectives (O): O1: Rigorous selection of appropriate NAMs and MDP targeting S. aureus or P. aeruginosa. O2: Methodical production and characterization of PLGA NPs incorporating NAMs or PDM, ensuring reproducibility. O3: Modification of PLGA NPs’ surface to enhance bacterial specificity and uptake via integration of phage proteins and CPPs. O4: Comprehensive assessment of in vitro efficacy of the nanocarrier for delivering NAMs or MDP into bacteria. O5: Evaluation of the most promising nanoformulation through in vivo efficacy studies via intra-hemocoel application. These objectives will be realized through collaboration among a multidisciplinary team possessing expertise in NP formulation, NAM design and production, MDP extraction and purification, as well as phage protein characterization and production. Methodologies employed to achieve these objectives encompass four research tasks alongside two tasks dedicated to project dissemination and management: 1. Selection of bioactive molecules against S. aureus and P. aeruginosa 2. Production and characterization of stable NPs to encapsulate NAMs/PDM 3. Modification of the NPs’ surface with phage proteins and CPPs 4. Evaluation of the nanoformulation’s efficacy and safety in vitro and in vivo 5. Project management and coordination 6. Project dissemination To ensure the project's success, a risk management plan was elaborated (Table 1). The envisaged workplan anticipates yielding scientifically significant outcomes of international relevance, harmonized with the UN Goals (2030 Agenda) objectives, particularly Goals 3 and 17. Also, the project's deliverables are poised to fortify synergies among research groups operating in mutually complementary domains encompassing nanotechnology, biological engineering, microbiology, and molecular biology. Leveraging prior collaborative efforts within the NanoBiBact team, notably through prior engagement in an exploratory project funded by the FCT addressing analogous themes, underscores the trajectory towards anticipated project advancement.