Stealth nanoparticles: high density but sheddable PEG is a key for tumor targeting

Abstract

There are three major requirements for a nanoparticle to deliver its payload to the tumor. First, the particles need to be stable in the circulation without releasing the drug prematurely. Second, the nanoparticles accumulate in the tumor efficiently. Third, the drug is released locally in the tumor tissue or inside the tumor cells. A variety of approaches have been developed to fulfill these requirements. In this perspective, we will discuss them together with some examples.

Figure 1

Comparison of the pharmacokinetic profiles of the PEGylated LPD (A) and the SPLP (B) in animal models. Non-targeted NP = PEGylated LPD and targeted NP = PEGylated LPD with surface decoration of a targeting ligand, anisamide. Data are reproduced from (–5) with permission.

Figure 2

Proposed mechanisms for the biodistribution and the drug release of the liganded and PEGylated LPD nanoparticles. A. The liganded and PEGylated LPD is introduced intravenously with brushed PEG that prevents opsonization at the initial period of time, allowing the nanoparticles to extravasate efficiently to the tumor with a leaky vasculature. B. The PEG-lipid gradually sheds from the LPD, leading to increased protein binding, RES uptake and accelerated clearance from the blood. C. After cellular internalization, the cationic lipid membrane interacts with the endosomal membrane via ion-pairing after de-PEGylation, causing membrane fusion and payload release.