
11, 12 Compared to preexisting carriers such as liposome and niosomes, SLNs exhibit the advantage of enhanced encapsulation efficiency for hydrophobic drugs, long colloidal stability, excellent reproducibility, and low drug leakage. These can be performed through careful tuning of size, surface charge, lipid composition, molecular weight, length of PEGylation, and so on. 10 Third, the formulation of SLNs can be modified to achieve different drug-delivering parameters, including bioavailability, half-life, and diffusing rate. 9 Alternatively, the use of phospholipids and ionizable lipids promotes the delivery of hydrophilic drugs. 5 Second, the lipid core allows efficient delivery of lipophilic small molecule drugs with high bioavailability and low toxicity. As almost all components of SLNs can be made bio-native, low immunogenicity is present at the nano-bio interface. First, SLNs are biocompatible and easily biodegradable. 7, 8 SLNs exhibit several advantages that make them promising nanomedicine candidates. 7 Such versatile core–shell structure allows for specialized transportation of both lipophilic and hydrophilic drugs to enhance bioavailability and reduce toxicity. Generally speaking, SLNs consist of a solid lipid core surrounded by surfactants and cosurfactants to improve their colloidal stability. In addition, several RNA-encapsulated SLN formulations are currently undergoing FDA clinical trial. 5 The popularity of SLNs has been greatly promoted by the advent of COVID-19 vaccines which owe their success to SLNs that took decades to refine. 4 Among the key members of nanomedicine, solid lipid nanoparticles (SLNs) are a type of novel lipid-based pharmaceutical formulation and are considered promising in improving drug delivery efficiency. 2, 3 As such, nanomedicine is expected to revolutionize modern pharmaceutical industry. 1 Compared to traditional methods, nanomedicine shows improved delivery efficiency, decreased toxicity, and much higher versatility for a great variety of cargos. Nanomedicine holds great potential as a novel drug delivery platform. This work opens up ways to address critical questions in SLN drug delivery and could also facilitate innovations in lipid nanotechnology and clinical translations. Our bioorthogonal chemical imaging modality by SRS microscopy can be generalized to visualize a wide spectrum of lipid-based drug carriers with high spatiotemporal resolution, chemical specificity, and ultimate sensitivity. Notably, with this approach, we have achieved ultrahigh single-particle sensitivity both in vitro and in vivo, even with particle counting ability. The introduction of deuterium to lipid structure renders bioorthogonal chemical specificity. Here, we present close-to-label-free imaging of deuterated SLNs using the emerging stimulated Raman scattering (SRS) microscopy. Despite the increasing impact, the characterization methods of SLNs are currently very limited especially in biological environment, which hinders fundamental understanding of the delivery mechanism and contributes to relatively low success rate in clinical translations. They became widely known in late 2020, as several COVID-19 vaccines are built upon SLNs technology.

Advantages of SLNs include high biocompatibility, low immunogenicity, superiority in drug encapsulation capacity, and improved colloidal stability. Solid lipid nanoparticles (SLNs) are a state-of-the-art lipid-based pharmaceutical drug delivery system.
