Artificial Organelles: Towards Adding or Restoring Intracellular Activity

Abstract

Compartmentalization is one of the main characteristics that define living systems. Creating a physically separated microenvironment allows nature a better control over biological processes, as is clearly specified by the role of organelles in living cells. Inspired by this phenomenon, researchers have developed a range of different approaches to create artificial organelles: compartments with catalytic activity that add new function to living cells. In this review we will discuss three complementary lines of investigation. First, orthogonal chemistry approaches are discussed, which are based on the incorporation of catalytically active transition metal‐containing nanoparticles in living cells. The second approach involves the use of premade hybrid nanoreactors, which show transient function when taken up by living cells. The third approach utilizes mostly genetic engineering methods to create bio‐based structures that can be ultimately integrated with the cell's genome to make them constitutively active. The current state of the art and the scope and limitations of the field will be highlighted with selected examples from the three approaches.

Block Length‐Dependent Protein Fouling on Poly(2‐oxazoline)‐Based Polymersomes: Influence on Macrophage Association and Circulation Behavior

“…Polymer-based vesicles, called polymersomes, [1] are promising nanomaterials with potential biomedical applications in drug delivery, immunotherapy, biosensing, and as nanoreactors and artificial organelles in vitro and in vivo. [2][3][4][5][6][7] However, clinical translation of polymersomes and, more broadly, many other nano medicines is hampered due to nano-bio interactions in biological environments. [3,8] These interactions with biological fluids (e.g., blood serum) change various nanoparticle properties such as stability, release behavior, cell uptake, and biodistribution.…”

Nanozyme‐Based Artificial Organelles: An Emerging Direction for Artificial Organelles

“…In addition, designing artificial organelles with adjustable activity is also an important problem in this field. [ 6 ] Considering the above shortcomings, natural enzymes cannot satisfy the demands of artificial organelles fabrication. This is the reason why we need nanozyme as the functional catalyst to enhance and refine the use of artificial organelles.…”

“…They also proposed that artificial organelles are created to add novel functionality to living cells. [ 6 ] However, before this lofty ideal is reached, there are still many unsolved practical problems of current artificial organelles such as limited functions, unregulated activities, and difficulty in targeting delivery.…”

Microliter Scale Synthesis of Luciferase‐Encapsulated Polymersomes as Artificial Organelles for Optogenetic Modulation of Cardiomyocyte Beating

“…[ 2 ] More recently, this concept has also been expanded to implement AO systems that can even add non‐native, orthogonal pathways for modulating cellular behavior. [ 3 ]…”