Reconstituted Lipid Nanoparticles (rLNPs): A Promising Avenue in Nanomedicine for Drug Delivery

Nanomedicine has emerged as a transformative field that amalgamates nanotechnology with life sciences, revolutionizing drug delivery and therapeutics. This interdisciplinary domain has witnessed remarkable advancements in research and development, with potential applications ranging from drug delivery to the formulation of life saving vaccines and wearable medical devices. Nanomedicine has paved the way for highly specific, effective, and personalized drug delivery systems, addressing the critical challenge of enhancing bioavailability while ensuring safety. Despite these major advancements, the development of nanoparticles-based drug delivery carriers still faces significant obstacles, such as achieving targeting to the cells of interest, reproducibility and scalability in manufacturing, and addressing pharmacological and safety concerns. As a result, only a handful of nanomedicine-based products have successfully overcome these obstacles and gained clinical approval.

Recently there has been a great interest in cell/tissue-based drug nanocarriers, such as cell membrane vehicles and exosomes. These carriers, which are derived from natural sources, offer the advantages of biocompatibility and circumvent issues related to immunogenicity and cytotoxicity. Furthermore, they can be tailored to overcome biological barriers for specific targeting. However, these carriers have some limitations of low yields and limited reproducibility, making them unsuitable for large-scale clinical applications, nevertheless, they have ignited a quest to explore novel cell/tissue-based drug carriers.

Lipid nanoparticles (LNPs), including solid lipid nanoparticles, nanostructured lipid carriers, and liposomes, have gained recognition for their biocompatibility, ease of production, and safety. These LNPs can be precisely customized for in vivo use, overcoming biological barriers to enable specific targeting. Consequently, LNPs have become one of the most promising platforms for clinical drug delivery. In light of these developments, Professor Cheng Wang from the School of Pharmacy at Changzhou University developed new reconstituted lipid nanoparticles (rLNPs).  This novel rLNPs approach involves extracting lipids from cells or tissues and preparing them into rLNPs using a solvent diffusion method. This innovative technique offers versatility, enabling the use of rLNPs in various cellular and tissue contexts. Additionally, rLNPs can be labeled with fluorescent molecules or modified with targeting ligands and other functional moieties to bestow them with imaging, cell/tissue targeting, or other specific functions. The new study is now published in the peer-reviewed Journal Molecular Pharmaceutics.

In his study, Dr Cheng Wang successfully demonstrated that rLNPs could be consistently prepared from both 4T1 cells (a mouse breast cancer cell line) and mouse liver tissue, yielding nanoparticles of approximately 20 nm in size. These rLNPs exhibited high stability in physiological environments, making them reliable candidates for drug delivery applications. Moreover, he was able to label rLNPs with fluorescent molecules and modify them with targeting ligands which is a significant advantage. This flexibility in functionalization allows for versatile applications of rLNPs in various research and clinical scenarios. The study also confirmed the high biocompatibility of rLNPs, as they exhibited negligible hemolysis risk, no significant cytotoxicity in vitro, and no adverse effects in vivo even at high doses. This establishes rLNPs as safe and well-tolerated drug carriers. When Dr Wang, tested rLNPs tumor accumulation and long-circulation properties, he demonstrated preferential accumulation of the rLNPs in tumor tissue and extended circulation in the bloodstream. This is critical for their efficacy in cancer therapy, as enhanced tumor targeting and prolonged drug release are critical for successful treatment. Furthermore, rLNPs displayed the capability to load different types of molecules, including hydrophilic and hydrophobic drugs. This versatility enhances their potential for various therapeutic applications. It is noteworthy to mention that the study reported that rLNPs loaded with Dox exhibited potent anticancer effects, surpassing the performance of free Dox. This highlights their potential as a drug delivery carrier for cancer treatment.

In conclusion, Dr Cheng Wang developed rLNPs as a new promising avenue in nanomedicine for drug delivery. These rLNPs offer numerous advantages, including high reproducibility, flexibility in labeling and modification, biocompatibility, preferential tumor accumulation, and versatile drug loading capabilities. The excellent in vitro and in vivo anticancer performance underscores rLNPs’ potential as a valuable addition to the arsenal of drug delivery carriers which might be further extended for the treatment of other diseases by loading other kinds of drugs. Additionally, the author also points out that rLNPs might have cell or tissue-specific homing or education functions which deserve further explorations.