Abstract
The research of lipid nanoparticles (LNPs) has been ongoing for more than three decades, and more research are still being carried out today. Being the first Food and Drug Administration (FDA)-approved nanomedicine, LNPs not only provide various advantages, but also display some unique properties. The unique lipid bilayer structure of LNPs allows it to encapsulate both fat-soluble and water-soluble molecules, hence enabling a wide range of possibilities for the delivery of therapeutic agents with different physical and chemical properties. The ultra-small size of some LNPs confers them the ability to cross the blood brain barrier (BBB), thus obtaining superiority in the treatment of diseases of the central nervous system (CNS). The ability of tumor targeting is one of the basic requirements to be an excellent delivery system, where the LNPs have to reach the interior of the tumor. Factors that influence tumor extravasation and the permeability of LNPs are size, surface charge, lipid composition, and shape. The effect of size, surface charge, and lipid composition on the cellular uptake of LNPs is no longer recent news, while increasing numbers of researchers are interested in the effect of shape on the uptake of LNPs and its consequential effects. In our study, we prepared three lipid nanostars (LNSs) by mixing phosphatidylcholine (PC) with different backbone lengths (C14:C4 or C16:C6 or C18:C8) at a 3:1 ratio. Although several star-shaped nanocarriers have been reported, these are the first reported star-shaped LNPs. These LNSs were proven to be safe, similar in size with their spherical controls (~100 nm), and stable at 37°C. The release rate of these LNSs are inversely related to the length of the lipid backbone. Most importantly, these LNSs exhibited greatly enhanced cellular uptake and in vivo tumor extravasation compared with their spherical controls. Based on the different uptake and pharmacokinetic characteristics displayed by these LNSs, numerous route formulations could be taken into consideration, such as via injection or transdermal patch. Due to their excellent cellular uptake and in vivo tumor accumulation, these LNSs show exciting potential for application in cancer therapy.
Highlights
Current strategies for cancer therapy include chemotherapy, surgery, angiogenesis, and monoclonal antibody therapy
The transmission electron microscope (TEM) results showed that the LNS14:4, LNS16:6, and LNS18:8 were star-shaped, and well distributed in water (Figure 1C)
We first prepared three lipid nanostars (LNSs) by mixing PC with different backbone lengths (C14:C4 or C16:C6 or C18:C8) at the ratio of 3:1, and confirmed that they exhibited largely enhanced cellular uptake and in vivo tumor extravasation compared with their spherical controls
Summary
Current strategies for cancer therapy include chemotherapy, surgery, angiogenesis, and monoclonal antibody therapy. The pores between endothelial cells allow nanoparticles to passively accumulate in tumors, which provides a new avenue for tumor targeting therapy. Various nanomedicine have been designed and approved to be reliable for cancer therapy, among them, lipid nanoparticles (LNPs) are the most timehonored nanomedicine and the pioneer to be applied clinically (Shi et al, 2017). LNPs have an aqueous inner part, and a surrounding of one or more concentric lipid bilayers. This unique structure allows LNPs to encapsulate both fat-soluble and water-soluble molecules, providing a wide range of possibilities to deliver therapeutic reagents with different physical and chemical properties (Khan et al, 2008). Other superiorities of LNPs include facilitated industrial production, suitable bioavailability (Din et al, 2015), biocompatibility (Eiras et al, 2017), improved drug absorption (Wang et al, 2017), and delayed dissolution (Xu et al, 2010)
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