Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance

Abstract

Nanotechnology has been extensively studied and exploited for cancer treatment as nanoparticles can play a significant role as a drug delivery system. Compared to conventional drugs, nanoparticle-based drug delivery has specific advantages, such as improved stability and biocompatibility, enhanced permeability and retention effect, and precise targeting. The application and development of hybrid nanoparticles, which incorporates the combined properties of different nanoparticles, has led this type of drug-carrier system to the next level. In addition, nanoparticle-based drug delivery systems have been shown to play a role in overcoming cancer-related drug resistance. The mechanisms of cancer drug resistance include overexpression of drug efflux transporters, defective apoptotic pathways, and hypoxic environment. Nanoparticles targeting these mechanisms can lead to an improvement in the reversal of multidrug resistance. Furthermore, as more tumor drug resistance mechanisms are revealed, nanoparticles are increasingly being developed to target these mechanisms. Moreover, scientists have recently started to investigate the role of nanoparticles in immunotherapy, which plays a more important role in cancer treatment. In this review, we discuss the roles of nanoparticles and hybrid nanoparticles for drug delivery in chemotherapy, targeted therapy, and immunotherapy and describe the targeting mechanism of nanoparticle-based drug delivery as well as its function on reversing drug resistance.

Keywords: drug delivery; drug resistance; hybrid nanoparticles; nanoparticle; targeted cancer therapy.

FIGURE 1

Different types of nanoparticles (NPs) for cancer therapy. NPs applied to drug delivery systems include organic NPs, inorganic NPs and hybrid NPs. The organic NPs contain liposome-based NPs, polymer-based NPs and dendrimers. Among polymer-based NPs, polymeric NPs and polymeric micelles are common. The inorganic NPs consist of gold NPs (Au NPs), carbon nanotubes, silica NPs, magnetic NPs, and quantum dots. Hybrid NPs combine the advantages of different NPs, including lipid-polymer hybrid NPs, organic-inorganic hybrid NPs, and cell membrane-coated NPs.

FIGURE 2

Passive and active targeting of NPs to cancer cells. Targeting of NPs enhance therapeutic efficiency and reduce systemic toxicity. Passive targeting of NPs is mainly achieved by the enhanced permeability and retention (EPR) effect, which exploits the increased vascular permeability and weakened lymphatic drainage of cancer cells and enables NPs to target cancer cells passively. Active targeting is achieved by the interaction between ligands and receptors. The receptors on cancer cells include transferrin receptors, folate receptors, glycoprotein (such as lectin), and epidermal growth factor receptor (EGFR).