Lipoproteins as drug delivery vehicles for cancer and tumor therapeutics

Abstract

Present article focuses on various lipoprotein based drug delivery vehicles used in cancer and tumor therapeutics. Starting from aqueous phase delivery through liposomes or unilamellar vesicles, biomimetic HDL nanoparticles, discoidal recombinant high-density lipoproteins (d-rHDLs) are favorably used to deliver anticancer agents. LDL based carrier vehicles are reconstituted in many ways i.e. discoidal SMAaf-based lipid nanoparticles, nanovectors, LDL nanoparticles, SiRNA-HDL used for systemic delivery of short interfering RNA. This article also explains chemically and genetically engineered highdensity lipoprotein (HDL)-like nanodiscs or "bicelles", chylomicrons, and monoclonal antibodies and ligand-coupled lipoprotein as drug delivery vehicles. These are most promising delivery systems for anticancer drugs. Acetylated low-density lipoprotein is also used as a delivery vehicle for anti-infectious drugs. There is immense need of therapies, imaging agents, and drug delivery vehicles to combat rising number of cases of neoplasticity and tumors in population. For safe cancer therapeutics nano-sized sitespecific drug delivery vehicles which might show bio-compatibility, bio-degradability, and receptor-mediated endocytosis are to be developed.

Tyloxapol and nanoliposomes induce selective delivery of 5‐fluorouracil into hepatic tissues via VLDL/LDL‐mediated pathway

“…The presence of cholesterol in 5‐FUC modifies the properties of liposomes and extends drug release. [ 32–34 ] Furthermore, the incorporation of cholesterol into lipid bilayers stabilizes and minimizes the systemic clearance of liposomes, [ 34,35 ] which could extend the contact time between the liposomes and lipoproteins to mediate drug transfer. Lipid‐based lipophilic formulations of nanoscale size and negative zeta potential previously showed extended drug plasma circulation time.…”

“…The presence of cholesterol in 5-FUC modifies the properties of liposomes and extends drug release. [32][33][34] Furthermore, the incorporation of cholesterol into lipid bilayers stabilizes and minimizes the systemic clearance of liposomes, [34,35] which could extend the contact time between previously showed extended drug plasma circulation time. [15] Interestingly, liposomes exhibit LDL tropism; LDL contains enzymes involved in liposomal phospholipid metabolism.…”

“…[4] Moreover, liposomes are taken up intracellularly by LDL receptors, parallel to lipoproteins. [35] Arroyo-Ariza et al indicated that the cellular uptake of liposomes could be mediated by LDL receptors overexpressed in tumor cells. [36] The transfer process of 5-FUC from the liposome to LDL surfaces is driven by thermodynamics or enzyme-dependent processes.…”

Crosstalk of low density lipoprotein and liposome as a paradigm for targeting of 5-fluorouracil into hepatic cells: cytotoxicity and liver deposition

“…Moreover, LDL particles have amphipathic surface consists of free cholesterol, and phospholipid monolayer wrapped by apoproteinB100 [ 4 , 6 ]. LDL nanoparticles act as cargoes of lipophilic materials in the blood as well as regulate the transport and metabolism of lipids and drugs [ 25 , 26 ]. LDL cargoes are trafficking into the intracellular environments through interaction between ApoproteinB100 and LDL-r by receptors mediated endocytosis [ 4 , 6 ].…”

“…In the bloodstream, drug cholesterol conjugates could be loaded into specific lipoproteins. Particularly, such conjugates are mimicking cholesterol esters as normal components of lipoproteins [ 4 , 10 , 25 ]. LDL-loaded drug conjugates could traffic into the cell through LDL-r mediated endocytosis similar to native LDL.…”