PEGylated liposomes: immunological responses

Abstract

A commonly held view is that nanocarriers conjugated to polyethylene glycol (PEG) are nonimmunogenic. However, many studies have reported that unexpected immune responses have occurred against PEG-conjugated nanocarriers. One unanticipated response is the rapid clearance of PEGylated nanocarriers upon repeat administration, called the accelerated blood clearance (ABC) phenomenon. ABC involves the production of antibodies toward nanocarrier components, including PEG, which reduces the safety and effectiveness of encapsulated therapeutic agents. Another immune response is the hypersensitivity or infusion reaction referred to as complement (C) activation-related pseudoallergy (CARPA). Such immunogenicity and adverse reactivities of PEGylated nanocarriers may be of potential concern for the clinical use of PEGylated therapeutics. Accordingly, screening of the immunogenicity and CARPA reactogenicity of nanocarrier-based therapeutics should be a prerequisite before they can proceed into clinical studies. This review presents PEGylated liposomes, immunogenicity of PEG, the ABC phenomenon, C activation and lipid-induced CARPA from a toxicological point of view, and also addresses the factors that influence these adverse interactions with the immune system.

Nanoparticles Loaded with the BET Inhibitor JQ1 Block the Growth of Triple Negative Breast Cancer Cells In Vitro and In Vivo

“…A well-recognized approach able to prolong the plasmatic half-life of a colloidal system is based on the coating of its surface by means of hydrophilic derivatives (as in the case of PEG) with the aim of decreasing its identification and elimination [27]. However, the multiple administration of PEG-coated systems determines the appearance of an accelerated blood clearance (the so-called ABC phenomenon) [28,29]. For this reason, the PLGA nanoparticles proposed in our work were developed by using the poloxamer 188 as a stabilizer because it can confer long circulating properties to the particles, avoiding the use of PEG [30,31].…”

Self-Assembly of Organic Nanomaterials and Biomaterials: The Bottom-Up Approach for Functional Nanostructures Formation and Advanced Applications

“…For this reason, in the last decades, the PEGylation process has become a standard in drug/nanocarrier functionalization for the development of advanced drug delivery systems [172,173]. However, a number of investigations has reported unexpected adverse immune responses such as the rapid clearance of PEGylated nanocarriers upon repeat administration, a phenomenon called accelerated blood clearance (ABC) [174]. In fact, the patients who undergo a treatment with PEGylated nanocarriers may stimulate the formation of antibodies that recognize (and bind) to PEG (i.e., anti-PEG antibodies) [174].…”

“…However, a number of investigations has reported unexpected adverse immune responses such as the rapid clearance of PEGylated nanocarriers upon repeat administration, a phenomenon called accelerated blood clearance (ABC) [174]. In fact, the patients who undergo a treatment with PEGylated nanocarriers may stimulate the formation of antibodies that recognize (and bind) to PEG (i.e., anti-PEG antibodies) [174]. Therefore, patients that acquire anti-PEG antibodies exhibit an accelerated blood clearance and a lower drug efficacy [174,175].…”

“…In fact, the patients who undergo a treatment with PEGylated nanocarriers may stimulate the formation of antibodies that recognize (and bind) to PEG (i.e., anti-PEG antibodies) [174]. Therefore, patients that acquire anti-PEG antibodies exhibit an accelerated blood clearance and a lower drug efficacy [174,175].…”

Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer

“…Another possibility for improving stability is the aptamers PEG conjugation. Furthermore, it has been shown that PEG formulation reduces immune responses in vivo [41]. The thermal stability of siRNA is another parameter to be considered in gene silencing activity when it is conjugated to aptamers [38].…”