Content area
Lipid-based nanomedicines are already widely used in antitumor therapy and gene delivery. However, their complex structural features demand advanced mesoscopic structural characterization tools for effective research and development (R&D) and quality control. Synchrotron small-angle X-ray scattering (SAXS) is a powerful, non-invasive technique for probing nanoscale membrane organizations, monitoring in situ dynamic membrane assembly, and exploring the interactions of components in lipid-based drug delivery systems, including liposomes, lipoplexes, lipid nanoparticles (LNPs), and lyotropic liquid crystals (LLCs). Recent advances in high-flux synchrotron facilities, high-frequency detectors, and automated SAXS data processing pipelines permit a detailed structural characterization of lamellarity, bilayer spacing, internal phases, core–shell morphology, as well as “pump-probe” dynamic process studies for lipid nanomedicines. Though major challenges remain in sample polydispersity and model fitting, the advances in time-resolved synchrotron SAXS, high-throughput automation, and artificial intelligence (AI)-assisted modeling are rapidly reducing this barrier. This review summarizes SAXS methodology and introduces representative case studies in the field of lipid nanomedicines. The performance of BioSAXS beamline BL19U2 in the Shanghai synchrotron radiation facility (SSRF) and prospects of AI-guided drug screening at BL19U2 are highlighted to advance intelligent R&D and quality control for lipid nanomedicines.
Details
Polydispersity;
Data processing;
Nanoparticles;
Quality control;
Liquid crystals;
Membrane structures;
Approximation;
Automation;
Research & development--R&D;
Lipids;
Structural analysis;
Membrane structure;
X-ray scattering;
Synchrotron radiation;
Crystals;
Sensors;
Gene transfer;
Drug delivery systems;
Quantitative analysis;
Particle size;
Drug screening;
Drug delivery;
Membranes;
Atoms & subatomic particles;
X-rays;
Small angle X ray scattering
1 Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Rd, Shanghai 200237, China; [email protected], National Facility for Protein Science Shanghai, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China; [email protected]
2 National Facility for Protein Science Shanghai, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China; [email protected]
3 Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Rd, Shanghai 200237, China; [email protected], National Center for Liver Cancer, The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China