Targeting tumor microenvironment with PEG-based amphiphilic nanoparticles to overcome chemoresistance

Abstract

Multidrug resistance is one of the biggest obstacles in the treatment of cancer. Several factors involves in drug resistance including enhanced repair mechanisms of drug induced DNA damage, lowered tumor extracellular pH, alteration of cell cycle check points, blockage of apoptosis pathway, poor tumor vasculature and over expression of drug efflux pumps. Recent research studies highlight that tumor microenvironment plays a predominant role in tumor cell proliferation and metastasis. Hence, targeting the tumor microenvironment provides a novel strategy for the evolution of cancer nanomedicine. The blooming knowledge about the tumor microenvironment merging with the design of PEG-based amphiphilic nanoparticles can provide an effective and promising platform to address the multidrug resistant tumor cells. This review describes the characteristic features of tumor microenvironment and their targeting mechanisms with the aid of PEG-based amphiphilic nanoparticles for the development of newer drug delivery systems to overcome multidrug resistance in cancer cells.

Biodistribution and Pharmacokinetics of Mad2 siRNA-loaded EGFR-Targeted Chitosan Nanoparticles in Cisplatin Sensitive and Resistant Lung Cancer Models

“…Many studies have associated PEG with greater tumor uptake and longer circulation time [62,63]. Besides, PEG contributes to increased par- ticle hydrophilicity, stability, avoidance of plasma protein identification and escape from opsonization and clearance [64]. When comparing tumor exposure to the sum of other organs exposure (Figure 6B), we observed that TE was high, with tumor exposure ranging between 28.3 and 49.0% of the global organ exposure.…”

Soft Interaction in Liposome Nanocarriers for Therapeutic Drug Delivery

“…Many studies demonstrated that PEGylated liposomes were able to improve the stability and blood-circulation time, together with low plasma clearance, and low volume of distribution (with minimal interaction with non-tumoural tissues) [64,65,66]. Chen et al [67] showed that plasma protein adsorption onto nanocarrier surfaces on PEG-coated nanocarriers strongly depends on the PEG chain length and density at the nanocarrier surface. …”

Therapeutic Efficacy of Nanocomplex of Poly(Ethylene Glycol) and Catechin for Dry Eye Disease in a Mouse Model

“…6,13 Poly(ethylene glycol) (PEG) is a nonionic and hydrophilic polymer widely used in various therapeutic biological drugs as a drug delivery system. [14][15][16][17] Poly(ethylene glycol)-based copolymers play a potential role as biomedical material for biomedical applications because they are biocompatible, biodegradable, and thermosensitive and have easily controlled properties. 18 In 2008, Mok et al 16 reported the applicability of nanocomplexes of PEG and biomacromolecules (such as proteins, DNA, and carbohydrates) for long-acting and sus-tained-release formulas of therapeutic biologic drugs.…”

“…18 In 2008, Mok et al 16 reported the applicability of nanocomplexes of PEG and biomacromolecules (such as proteins, DNA, and carbohydrates) for long-acting and sus-tained-release formulas of therapeutic biologic drugs. 16 Chen et al 17 also suggested that PEG-based amphiphilic nanoparticles can be used to overcome multidrug resistance in cancer cells via the development of a new drug delivery system. However, most studies of PEG are limited to the approach of material engineering, and the study of the efficacy of PEG is still inadequate.…”