A Safe, Versatile and Translation-prone Strategy for Using Circulating Lipoproteins as Endogenous Drug Delivery Systems
Abstract
Lipoproteins (LPs), the endogenous lipid-protein micro- and nanostructures involved in lipid metabolism, have attracted a high degree of interest in recent years for being used as novel drug delivery systems. Numerous diagnostic and therapeutic agents (in particular anti-cancer agents) have been studied using native and (semi)synthetic LPs as both prolonged and targeted drug delivery systems. Since all reported loading methods are basically in vitro or ex vivo procedures with related limitations, an idea has been raised for finding a completely new loading paradigm to overcome the limitations in using native particles as drug vehicles. The basis for this hypothesis is that we are able to load native and circulating LPs without extracting them from body via using specific monoclonal antibodies (MAb, already linked to desired drugs or to be linked to drug via proper linker system such as avidin-biotin bridges) actively-targeted against specialized Apos available on the surface of all LPs. Obviously, by choosing the right anti-Apo antibody (preferably single chain variable fragment; scFv), we can select the right circulating LP subpopulation (i.e., LDL, HDL, VLDL, or CM). By considering all parameters and using the most appropriate strategy, this novel, safe, versatile, industrializable, and clinically translation-prone paradigm could be used for both prolonged and (LP receptor- and non-LP receptor-) targeted drug delivery purposes.
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