Light-triggered rupture and magnetically driven transport of lipid vesicles for controlled release and directed delivery of therapeutics

Kumar, Vinit

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https://hdl.handle.net/2142/130167 Copy

Description

Title

Light-triggered rupture and magnetically driven transport of lipid vesicles for controlled release and directed delivery of therapeutics

Author(s)

Kumar, Vinit

Issue Date

2025-07-15

Director of Research (if dissertation) or Advisor (if thesis)

Feng, Jie

Doctoral Committee Chair(s)

Feng, Jie

Committee Member(s)

• Han, Bumsoo
• Smith, Kyle
• Pak, On Shun

Department of Study

Mechanical Sci & Engineering

Discipline

Mechanical Engineering

Degree Granting Institution

University of Illinois Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• lipid bilayers
• osmotic shock
• vesicles
• targeted drug delivery
• spontaneous curvature
• light-triggered vesicle rupture
• asymmetric oxidation
• vesicle explosion
• magnetically driven
• magnetic particles
• light-triggered release

Abstract

Targeted drug delivery and precision medicine systems are transforming the field of therapeutics by enabling precise targeting of specific cells and localized drug delivery, thereby minimizing systemic toxicity. Among the various platforms under investigation, lipid-based drug delivery systems have gained significant attention due to their inherent biocompatibility and versatility in transporting a wide range of therapeutic agents, including hydrophilic, hydrophobic, and amphiphilic drugs. Recent advancements in synthetic biology and microfluidics have further highlighted the potential of giant unilamellar vesicles (GUVs) as highly effective drug delivery vehicles. For successful biomedical applications, it is essential to achieve directed motion of these delivery vehicles and ensure controlled release of their contents at the microscopic scale. However, major challenges persist such as: 1) on-demand destabilization of GUVs to enable localized release at predetermined target sites, and 2) achieving precise controlled motion of GUVs to the target sites. Addressing these existing challenges is crucial to fully realizing the potential of GUVs-based drug delivery systems. In my dissertation, I present experiments and models that investigate the stability of GUVs in non-equilibrium environments, with the aim of achieving on-demand, localized release of their encapsulated contents. Application of osmotic imbalance across the vesicle membrane is a well-established mechanism for achieving vesicle rupture. Under hypotonic conditions (higher concentration of solute molecules inside vesicle), the water flows into the vesicle causing it to swell. Due to the swelling, the vesicle is stretched building up the stress in membrane which can result in membrane rupture and pore opening. To counter osmotic stress, depending on the degree of osmotic imbalance and vesicle size, lipid vesicles can respond in a number of ways: simple swelling with no membrane rupture event, a series of short-lived transient pores, long-lived pores, or irreversible bursting, \textit{i.e.} vesicle explosion. Although considerable advances have been made in understanding the vesicle dynamics in other regimes; vesicle explosion remains poorly understood. Specifically, no prior theoretical framework existed that could explain how osmotic imbalance could lead to explosion. In this dissertation, I developed a comprehensive biophysical model incorporating the impact of spontaneous curvature, to unify and explicate vesicle dynamics of all experimentally observed regimes of vesicle rupture under osmotic stress. Another strategy explored in this dissertation to destabilize the vesicle is the oxidation of lipid membranes achieved by exposure to reactive oxygen species generated through photosensitization. Under oxidative stress, differing degrees of vesicle destabilization, such as formation of nanopores, transient micron-sized pores, and vesicle explosion have been observed. Even though the occurrence of vesicle explosion via photo-induced oxidation has been known for decades, explanations of oxidative vesicle explosion are incomplete and fragmentary. This dissertation presents a series of systematic experiments to investigate the impact of photo-induced lipid oxidation on the stability of lipid vesicles. I developed a theoretical model which links the oxidation-induced drastic conformational changes in lipid molecular shape to the generation of spontaneous curvature which explains the experiments well. Moreover, favorable conditions for vesicle explosion to occur are identified. I summarized these findings through a phase diagram with analytical criterion delineating transient pore formation and vesicle explosion. Additionally, I also explored methods to achieve controlled motion of GUVs for targeted delivery. Specifically, I investigated the motion of GUVs driven by an encapsulated magnetic microparticle under the influence of an external non-uniform magnetic field. By leveraging this approach, I demonstrated the active transport of GUVs, enabling targeted delivery to specific locations. This approach showcases the potential of magnetic fields as a non-invasive tool for manipulating vesicle dynamics. Through systematic experiments, I characterized the motion of GUVs propelled by an encapsulated magnetic particle (magGUVs) under the influence of an inhomogeneous magnetic field, validating the precision and controllability of this method. The experimentally obtained speed of GUVs is compared with simulations based on a lattice Boltzmann approach. Building on this, I further established a proof-of-principle for integrating the directed motion of magGUVs with controlled, localized release of their encapsulated contents. This was achieved by disrupting the GUVs through light-induced asymmetric oxidation, enabling precise spatiotemporal control over the cargo release. As GUVs serve as a ubiquitous cell-mimetic system, the insights gained from this research into their response and stability under non-equilibrium conditions could significantly enhance our understanding of biomembrane stability. This knowledge is particularly relevant in the context of the constant environmental stresses that cells encounter, offering a deeper perspective on how biological membranes maintain integrity and function under such assaults. The oxidation of the cell membranes via photosensitization has been explored in photodynamic therapy to selectively kill the diseased and cancer cells. The findings from this research could contribute to the development of strategies in photodynamic therapies, enhancing its precision and efficacy. Overall, these findings highlight the potential of combining light-triggered release with magnetic guidance mechanisms, offering a versatile and innovative platform for targeted therapeutic applications.

Graduation Semester

2025-08

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/130167

Copyright and License Information

Copyright 2025 Vinit Kumar

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