Physical Chemistry of Biological Systems and Biointerfaces

Module Theranostic and Nanomedicine (Module 2)

Course Description. The course addresses the physicochemical principles governing interactions between surfaces, nanomaterials, and biological systems, with particular emphasis on biointerfaces and nano-biointerfaces. It examines the role of intermolecular interactions and water, surface chemistry and structure, adsorption and molecular recognition processes, and interactions with biomolecules and cells. The course also covers biomaterials, biomimetic and bioinspired systems, nanoparticles, and nanozymes, with applications in nanomedicine, theranostics, biosensing, and imaging. Teaching activities integrate theoretical lectures, quantitative exercises, and experimental activities focused on the synthesis, characterization, and functional assessment of nanomaterials and nano-biohybrid systems.

Learning Objectives. The course provides advanced knowledge of the physicochemical foundations of biointerfaces and develops the ability to correlate molecular interactions, surface properties, nanomaterial structure, and biological response. In particular, students will acquire knowledge and skills in:

• the principles governing interactions between materials, biomolecules, and cells, with particular emphasis on the role of water and non-covalent interactions;
• the relationships between surface chemistry, charge, wettability, topography, and mechanical properties and the behavior of biointerfaces;
• principles of biomimetics, bioinspiration, self-assembly, and nano-biointerfaces;
• the design and applications of functional nanomaterials and nanosystems for drug delivery, biosensing, imaging, and theranostics;
• the main approaches and techniques for the physicochemical characterization of surfaces, biointerfaces, and nanomaterials;
• principles of the green synthesis of metallic and metal oxide nanoparticles, their characterization, and the assessment of their functional properties;
• the design and interpretation of simple experiments using model systems;
• correlations between synthesis, structure, surface properties, and nanomaterial function;
• applications of biointerfaces and nanomaterials in biomedical, environmental, and energy-related fields, with consideration of sustainability and safety aspects.

Information for Students with Disabilities and/or Specific Learning Disorders (SLD). Students with disabilities and/or specific learning disorders (SLD) may benefit from the support measures provided by current legislation and University services, according to their individual needs and the arrangements agreed upon with the competent University structures.

D1 – Knowledge and understanding. The student will acquire knowledge of the main physicochemical principles and models governing biointerfaces, understanding the role of intermolecular interactions, water, molecular organization, and surface properties in interactions between materials and biological systems. The student will also acquire knowledge of the principles of biomaterials, biomimetic and bioinspired systems, functional nanomaterials, and nano-biointerfaces, with particular emphasis on biomedical applications.

D2 – Applying knowledge and understanding. The student will be able to apply physicochemical principles and models to the interpretation of interfacial phenomena and to correlate the structure and properties of nanomaterials with their function. The student will also be able to apply basic strategies for the synthesis, characterization, and functional assessment of nanomaterials, and to interpret experimental data relating to sensing, drug delivery, and catalysis systems.

D3 – Making judgements. The student will be able to select appropriate experimental approaches and characterization techniques for the study of biointerfaces and nanomaterials, critically evaluating results, limitations, and the main sources of uncertainty. The student will also be able to consider the sustainability, safety, and potential applications of the systems studied.

D4 – Communication skills. The student will be able to describe and discuss physicochemical phenomena, experimental procedures, and results related to biointerfaces and nanomaterials, using appropriate scientific terminology, including in interdisciplinary contexts.

D5 – Learning skills. The student will be able to use specialized textbooks, scientific literature, databases, and other documentary resources to independently explore emerging topics and transfer the knowledge acquired to new problems in the field of biointerfaces and nanomaterials.

The course consists of lectures, numerical exercises, and laboratory activities. Lectures and numerical exercises are held in the classroom using a projector and whiteboard, while laboratory activities are carried out in the Department’s teaching and experimental facilities.

Students from EUNICE partner universities other than UNICT who participate in the EUNICE Excellence Programme – Bioinspired Chemistry may attend the course remotely via Moodle and Microsoft Teams. If the course is delivered in a blended format, the necessary organizational adjustments may be made while maintaining the contents and learning objectives defined in the syllabus.

Basic knowledge of mathematics, physics, general chemistry, physical chemistry, organic chemistry, and biochemistry. A basic understanding of the main concepts of physical chemistry of surfaces and interfaces is also expected, particularly intermolecular interactions, surface properties, and adsorption phenomena. Basic knowledge of materials science, nanomaterials, and characterization techniques is useful, but not essential.

Attendance is governed by the Academic Regulations of the Degree Programme.

Course Contents

1. Physicochemical foundations of biointerfaces. Definition and classification of biointerfaces. Thermodynamic and physicochemical properties of surfaces and interfaces. Role of water and hydration at biointerfaces. Electrostatic, van der Waals, hydrophobic, and specific interactions. Interfacial free energy, wettability, and surface properties. Adsorption and organization of biomolecules at surfaces. Protein corona and the concept of the biological identity of nanomaterials.

2. Biomaterials, extracellular matrix, and hydrogels. Structure and physicochemical properties of the extracellular matrix (ECM). Cell–ECM and cell–material interactions. Natural and synthetic biomaterials. Hydrogels and soft biomaterials: structure, hydration, swelling, viscoelastic properties, and interactions with biomolecules and cells. Relationships between material composition, structure and properties, and biological response. Bioactive, antifouling, and biomimetic surfaces.

3. Biomimetic systems and bioinspired chemistry. Principles of biomimetics and bioinspired chemistry. Nature-inspired strategies for molecular recognition, self-organization, catalysis, and energy conversion. Thermodynamic and kinetic principles of self-assembly. Biological membranes and lipid–surface interactions. Supported lipid bilayers (SLBs) as model systems for studying biointerface phenomena. Design of bioinspired surfaces, interfaces, and nanomaterials.

4. Nano-biointeractions and the biological fate of nanomaterials. Interactions between nanomaterials, biomolecules, and cells. Role of size, morphology, composition, surface charge, and functionalization in nano-bio interactions. Adsorption and rearrangement of biomolecules on nanomaterial surfaces. Protein corona and remodeling of the nano-bio interface. Mechanisms of cellular internalization and intracellular trafficking. Fundamentals of biodistribution, biotransformation, and clearance. Interactions with the immune system and the biological microenvironment.

5. Bioinspired nanomaterials and nanozymes. Principles for the design of bioinspired and functional nanomaterials. Structure–property–function relationships in nanomaterials. Nanozymes and biomimetic catalysis: principles, mechanisms, and factors determining catalytic activity. Role of composition, structure, surface properties, and interfacial environment. Applications of nanozymes in biosensing, diagnostics, and therapy. Stimuli-responsive nanosystems.

6. Nanomedicine and drug delivery systems. Physicochemical principles of nanomedicine and drug delivery. Properties and main classes of nanocarriers: lipid-based, polymeric, metallic, inorganic, and hybrid systems. Drug–nanocarrier interactions and encapsulation, adsorption, and conjugation processes. Passive and active targeting. Controlled release and stimuli-responsive delivery. Nanosystems for the delivery of small molecules, proteins, peptides, and nucleic acids/RNA. Relationships between nanocarrier properties, interactions with the biological environment, and delivery performance.

7. Nanodiagnostics, biosensing, and bioimaging. Physicochemical principles of biosensing and bioimaging using nanomaterials. Plasmonic, fluorescent, and photonic nanoparticles. Optical and spectroscopic properties of nanomaterials and their dependence on size, morphology, aggregation, and interfacial environment. Molecular recognition and signal amplification strategies. Applications in biosensing, imaging, and molecular diagnostics.

8. Theranostics and multifunctional nanosystems. Principles of theranostics and integration of diagnosis and therapy using multifunctional nanosystems. Strategies for combining targeting, imaging, and treatment. Stimuli-responsive nanosystems. Photothermal and photodynamic therapy and nanocatalysis as therapeutic approaches. Relationships between nanomaterial physicochemical properties, nano-bio interactions, and functional response. Applications in oncology and precision medicine.

9. Physicochemical characterization and experimental activities. Principles and applications of techniques for the physicochemical, spectroscopic, surface, colloidal, and morphological characterization of biointerfaces and nanomaterials. Analysis and interpretation of experimental data, with particular emphasis on correlating composition, structure, surface properties, interactions with biological systems, and function.

The experimental activities include the following laboratory experiments:

Laboratory Experiment 1. Solubilization of curcumin using micellar systems and experimental determination of the critical micelle concentration (CMC). Analysis of the role of hydrophobic interactions, hydration, and supramolecular organization in solubilization processes and drug delivery strategies.

Laboratory Experiment 2. Synthesis of silica nanoparticles (SiO₂ NPs) containing fluorescein isothiocyanate (FITC) and Rhodamine B (RhB). Study of the optical and surface properties of the nanosystems and analysis of the influence of structure and functionalization on fluorescence properties, with reference to potential applications in imaging and drug delivery.

Laboratory Experiment 3. Synthesis of gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) and investigation of their optical and plasmonic properties. Analysis of the influence of particle size, aggregation state, and interfacial environment on optical properties, and application of the nanosystems to colorimetric sensing.

Laboratory Experiment 4. Synthesis and characterization of magnetite nanoparticles (Fe₃O₄ NPs) and investigation of their nanozyme activity, with particular emphasis on catalytic properties. Characterization by UV–Vis spectroscopy, ATR-FTIR spectroscopy, contact angle measurements, and laser scanning confocal microscopy (LSM). Analysis of the relationships between composition, structure, surface properties, and functional activity of the nanosystems.

The experimental activities are aimed at developing students’ ability to design and perform simple experiments, acquire and analyze data, critically evaluate experimental results, and establish relationships between the structure, properties, and function of the systems investigated.

Core Textbooks

• P. Atkins, J. de Paula, Physical Chemistry for the Life Sciences, Oxford University Press, 2011.

• H. Ohshima, Biophysical Chemistry of Biointerfaces, John Wiley & Sons, Inc., 2010.

• B. D. Ratner, A. S. Hoffman, F. J. Schoen, J. E. Lemons, Biomaterials Science: An Introduction to Materials in Medicine, 4th ed., Academic Press/Elsevier, 2020.

Course Materials

• Lecture slides and teaching materials prepared by the instructor and made available through the course platform. These materials complement and expand upon the topics covered in lectures, with particular emphasis on biointerfaces, bioinspired chemistry, nano-bio interactions, nanozymes, nanomedicine, drug delivery, biosensing, bioimaging, and theranostics, as well as the experimental activities.

Further Reading

• Recent scientific articles and review papers selected by the instructor on biointerfaces, bioinspired chemistry, nano-bio interfaces, protein corona, nanozymes, nanomedicine, drug delivery, biosensing, bioimaging, and theranostics.

• Selected textbooks, experimental protocols, and scientific articles supporting the laboratory activities.

Assessment consists of an individual oral examination, aimed at verifying the acquisition of the knowledge and skills expected from the course.

During the examination, the topics covered in the course will be discussed, and students will be required to solve and discuss numerical exercises, similar in type to those carried out during the classroom exercises.

The examination will also include a discussion of the laboratory activities, based on the written reports and/or presentation of experimental results, with particular emphasis on data interpretation and on establishing correlations between physicochemical properties and function.

The assessment may also be conducted remotely, if required by circumstances, in accordance with the procedures established by the University.

Examples of typical questions and/or exercises:

•     Calculation of the surface coverage of a nanoparticle by a protein in a side-on configuration.

•     Surface tension, surface free energy, and wettability of an antifouling biomaterial.

•     Determination of the critical micelle concentration (CMC) and analysis of the solubilization of a hydrophobic compound.

•     Interpretation of the optical and plasmonic properties of metallic nanoparticles using UV–Vis data.

•     Analysis of the kinetics of a reaction catalyzed by a nanozyme.

•     Selection and interpretation of techniques for the characterization of biointerfaces and nanomaterials.

•     Principles of biosensing using optical and/or acoustic techniques.

•     Interpretation of experimental data obtained during the laboratory activities.