NUS I-FIM researchers assemble the first review that sheds light on the material-assisted engineering of isolated organelles for biomedical applications.
The world of cellular biology is vast and complex—each cellular component, no matter how minuscule, plays a specific and instrumental role, working together to make life possible. At the heart of this intricate ecosystem lie organelles, the microscopic powerhouses that drive cellular functions.
Delving deep into organelles, researchers from the Institute for Functional Intelligent Materials (I-FIM) at the National University of Singapore (NUS) have taken a deep dive into the world of these organelles. Their comprehensive review, published in ACS Materials Letters, not only sheds light on the innovative strategies to engineer these cellular components but also serves as a roadmap for future research.
The review highlights four distinct approaches currently employed to engineer isolated, intracellular organelles, while underscoring the potential of both natural and human-made materials in enhancing the capabilities of these organelles. The insights gleaned are expected to spur further development in organelle engineering, bringing to the fore more efficient theragnostics—a treatment strategy that combines therapeutics with diagnostics to enable more targeted and effective treatments, especially for complex diseases like cancer.
A bird’s-eye view of the world of intracellular organelles
Just like how our bodies contain many vital organs, our cells are like tiny microcosms of our bodies. Within each cell are organelles, each with a designated role, ensuring smooth cellular operations that, in turn, power our bodily functions. While the study of extracellular organelles, such as exosomes—tiny vesicles secreted by cells that facilitate cell-to-cell communication—has been extensive, the spotlight is now expanding, thanks to advances in cellular biology and nanotechnology, to include their intracellular counterparts.
“Intracellular organelles like mitochondria, thylakoid and lipid droplets, with their unique functionalities, offer a treasure trove of possibilities in healthcare,” said Professor Liu Bin, a principal investigator at NUS I-FIM. “Through some ingenious tweaks of engineering, we can amplify their natural capabilities, opening doors to innovative biomedical applications.”
“That’s why it’s crucial to maintain a bird’s-eye view on the current state of the art,” added Prof Liu, who is also a Distinguished Professor at the Department of Chemical and Biomolecular Engineering, NUS. “While many reviews have explored intracellular organelle imaging and treatment, or the modification of extracellular exosomes, ours is the first that focuses on the material-assisted engineering of isolated organelles for biomedical applications.”
The review drills down into four biocompatible strategies employed to engineer organelles. Take electrostatic interaction, for instance. It operates on the principle of charges attracting each other—much like how magnets work. Here, mitochondria, often referred to as the “energy factories” of cells due to their role in energy production, come into play. Their negatively charged membrane is drawn to positively charged polymers, enhancing their cellular integration and modifying their surface charge to better suit certain cellular activities.
Leveraging hydrophobic interactions, specific compounds nestle within the lipid bilayers of organelles, akin to a protective cocoon. Lipid droplets, the cell’s reservoirs for fats and energy, are particularly impacted by this mechanism. This confinement enhances certain functionalities, such as fluorescence. It also plays an important role in storing and releasing lipid-soluble drugs, ensuring their precise delivery where needed.
Covalent conjugation, the third strategy, can be likened to forming a permanent bond. Here, specific molecules such as nanoparticles are tethered covalently to organelles. Covalent bonds are chemically strong, ensuring a stable and lasting modification that enables scientists to perform certain tasks such as tracking and monitoring these organelles in real time, which offers invaluable insights into their movement and function.
Lastly, lipid fusion involves the merging of lipid membranes, creating hybrid structures with augmented capabilities. Thylakoids, integral components of plant chloroplasts responsible for photosynthesis, serve as a prime example. When integrated with other human vesicles, thylakoids can emulate the role of chlorophyll in plants. This fusion generates oxygen species crucial in cancer treatments—addressing oxygen deficiencies in tumours and enhancing therapeutic outcomes.
Engineering the organelles of tomorrow
The potential of organelle engineering cannot be overstated. However, it’s not without its hurdles. One of the primary challenges is the reliance on direct injections into lesions, a method that might not be sustainable or efficient for broader clinical applications.
Additionally, the physiological ramifications of introducing engineered organelles into living systems remain a grey area. Questions arise: How will these modified organelles interact with our natural cellular machinery? Will there be unintended consequences?
It’s also imperative that modifications to organelles are both biocompatible and biodegradable. Biocompatibility averts adverse body reactions, while biodegradability ensures they break down naturally, preventing long-term accumulation or potential harm. Both are crucial for patient safety and the effectiveness of organelle engineering. Importantly, the process also needs to be scalable.
Yet, as the adage goes: every challenge is an opportunity. The evolution of organelle painting techniques, where organelles are labelled for easy identification, is expected to usher in more streamlined engineering strategies. This, in turn, could unlock a diverse range of organelle-based treatments, expanding the tools available to healthcare professionals. Moreover, as researchers delve deeper, entirely new treatment modalities could be uncovered, pushing the boundaries of what’s currently possible in biomedicine.
“We believe our review will catalyse progress in organelle engineering. Integrating these techniques with foundational cell biology concepts could lead to new, innovative materials designed specifically for diagnostic and therapeutic applications,” added Prof Liu.