Synthetic low-density lipoprotein (sLDL) selectively delivers paclitaxel to tumor with low systemic toxicity

Abstract

Low density lipoprotein (LDL), which is a principal carrier for the delivery of cholesterol, has been used as a great candidate for the delivery of drugs to tumor based on the great requirements for cholesterol of many cancer cells. Mimicking the structure and composition of LDL, we designed a synthetic low-density lipoprotein (sLDL) to encapsulate paclitaxel-alpha linolenic acid (PALA) for tumor therapy. The PALA loaded sLDL (PALA-sLDL) and PALA-loaded microemulsion (PALA-ME, without the binding domain for LDLR) displayed uniform sizes with high drug loading efficiency (> 90%). In vitro studies demonstrated PALA-sLDL exhibited enhanced cellular uptake capacity and better cytotoxicity to LDLR over-expressed U87 MG cells as compared to PALA-ME. The uptake mechanisms of PALA-sLDL were involved in a receptor mediated endocytosis and macropinocytosis. Furthermore, the in vivo biodistribution and tumor growth inhibition studies of PALA-sLDL were investigated in xenograft U87 MG tumor-bearing mice. The results showed that PALA-sLDL exhibited higher tumor accumulation than PALA-ME and superior tumor inhibition efficiency (72.1%) compared to Taxol® (51.2%) and PALA-ME (58.8%) but with lower toxicity. These studies suggested that sLDL is potential to be used as a valuable carrier for the selective delivery of anticancer drugs to tumor with low systemic toxicity.

Recent Development of LDL-Based Nanoparticles for Cancer Therapy

“…Su et al prepared sLDL to encapsulate paclitaxel-alpha linolenic acid (PALA) for tumor therapy. PTX-loaded nano-drug PALA-sLDL had a suitable size (approximately 66 nm) and high loading efficiency, and a good tumor growth inhibitory effect in U87 MG mice [ 48 ]. Qian et al connected the lipid binding motif of apoB-100 to one end of PEG and introduced folate acid (FA) as a tumor-targeting moiety to the other end of PEG, constructing targeted folate receptor (FR) LDL bionic nanoparticles [ 34 ].…”

Biomimetics: reconstitution of low-density lipoprotein for targeted drug delivery and related theranostic applications

“…Compared to the established methods for the reconstitution of LDL particles, the fabrication of LMPs is relatively more complex as multiple components are needed to maximally mimic the structure of native LDL. 25 If the LMPs are not equipped with the LDL receptor-binding moiety, specific ligands are required to decorate the resultant nanoparticles for targeted drug delivery. 26 Similar to core reconstitution, this method allows for the incorporation of a large quantity of payloads.…”

Synthetic lipoprotein as nano-material vehicle in the targeted drug delivery

“…So, this aided their eradication. Su et al (2016) designed a synthetic LDL (sLDL) for encapsulating PTX-alpha linolenic acid (PALA), which was used for tumor therapy. Compared with PALA-loaded microemulsion (PALA-ME), it was showed by in vitro studies that PALA-loaded sLDL (PALA-sLDL) exhibited the enhanced cellular uptake capacity and better cytotoxicity to LDLR over-expressed U87 MG cells.…”