Effect of Glucose on Liposome–Plasma Protein Interactions: Relevance for the Physiological Response of Clinically Approved Liposomal Formulations

Abstract

Recently, the concept is emerging that the reduced success of nanoparticles in clinical practice is due to the adsorption of the “biomolecular corona (BC),” which alters their biological identity. Apart from protein variations, alterations in the human metabolome may change the BC decoration, which has poorly been addressed so far. Here, glucose is used as a model metabolite and how the interactions between liposomes (as a model nanoparticle) and plasma proteins are influenced by normal and diabetic sugar blood levels is explored. As model liposomes, Doxoves and Onivyde are used that are used for the treatment of breast and metastatic pancreatic cancer, respectively. It is shown that glucose does affect the structure and composition of BC. The biological effects of liposome–BC complexes are investigated in MCF 7 and MDA‐MB‐231 breast cancer cells for Doxoves and in pancreatic adenocarcinoma (PANC‐1) and insulinoma (INS‐1) cells for Onivyde. In the presence of glucose, the cellular toxicity of liposome–protein complexes and uptake by human monocytic THP1 cell line increases. These results demonstrate that alterations in glucose concentration, and more generally changes in the human metabolome, may play a fundamental role in the biological identity of liposomes and, consequently, on their in vivo physiological readouts including therapeutic efficacy.

Fluorescence Lifetime Nanoscopy of Liposomal Irinotecan Onivyde: From Manufacturing to Intracellular Processing

“…The position of this latter was inferred by fitting the data of Figure 2 C and resulted in a monoexponential lifetime ( Figure 2 D) of about 6.55 ± 0.46 ns (see also Table 1 ). The strong similarities between encapsulated irinotecan and encapsulated doxorubicin (i.e., Doxil) in terms of both lipid composition and drug active loading procedures 28 prompted us to speculate that the third species in Onivyde could correspond to a fraction of irinotecan molecules interacting with the liposome membrane. Worthy of note, the three-species reference system ( Figure 2 E) highlights the absence of free-in-solution irinotecan in the manufacturer’s formulation, a finding not entirely surprising based on irinotecan poor water solubility (approx.…”

“…Despite the significant progress in the development of drug-delivery nanoparticles for clinical applications, a thorough understanding and control of their complex physicochemical properties remains a challenging task. , This largely stems from the lack of analytical tools that can quantitatively dissect the molecular organization of the drug within the formulation throughout the process from manufacturing (synthetic identity) , to administration and final fate (biological identity). , The resulting lack of knowledge in turn limits our understanding of the performance of nanoencapsulated drugs in current delivery applications and our ability to propose new formulations by rational design. Here, we build on a recently validated FLIM-based approach to describe the nanoscale supramolecular organization of irinotecan in the FDA-approved liposomal formulation Onivyde.…”

Focused role of nanoparticles against COVID-19: Diagnosis and treatment

“…Combining these proposed Nano-based diagnostic approaches with advanced supervised classifiers, the patterns of biomolecules (comprising proteins, nucleic acids, metabolomes, and lipids) characterized by fatal risk diagnostic capacity will be defined [ 29 ]. Also, recent studies [ 98 , 99 ] reported a variation of nonprotein biomolecules (e.g., metabolomes) can considerably modify the corona composition of proteins, which can further enhance the diagnostic capacity of the corona sensor array system. In addition, by integrating the protein corona sensor array system with other sensor array elements, its diagnostic accuracy becomes enhanced.…”

Application of Non-Viral Vectors in Drug Delivery and Gene Therapy

“…Molecules such as folate and sugars also serve as ligands for liposomes [ 190 , 191 , 192 ]. There are also studies devoted to the development of liposome carriers modified with various ligands, multivalent ligands have multiple binding groups and enhance the therapeutic efficacy of drugs [ 193 ].…”