Application of active targeting nanoparticle delivery system for chemotherapeutic drugs and traditional/herbal medicines in cancer therapy: a systematic review

Abstract

Patients treated with conventional cancer chemotherapy suffer from side effects of the drugs due to non-selective action of chemotherapeutic drugs to normal cells. Active targeting nanoparticles that are conjugated to targeting ligands on the surface of nanoparticles play an important role in improving drug selectivity to the cancer cell. Several chemotherapeutic drugs and traditional/herbal medicines reported for anticancer activities have been investigated for their selective delivery to cancer cells by active targeting nanoparticles. This systematic review summarizes reports on this application. Literature search was conducted through PubMed database search up to March 2017 using the terms nanoparticle, chemotherapy, traditional medicine, herbal medicine, natural medicine, natural compound, cancer treatment, and active targeting. Out of 695 published articles, 61 articles were included in the analysis based on the predefined inclusion and exclusion criteria. The targeting ligands included proteins/peptides, hyaluronic acid, folic acid, antibodies/antibody fragments, aptamer, and carbohydrates/polysaccharides. In vitro and in vivo studies suggest that active targeting nanoparticles increase selectivity in cellular uptake and/or cytotoxicity over the conventional chemotherapeutic drugs and non-targeted nanoparticle platform, particularly enhancement of drug efficacy and safety. However, clinical studies are required to confirm these findings.

The Impact of New Targeting Methods in the Cancer Therapy

“…The past thirty years have seen progressively rapid developments in the field of targeted anticancer drugs. The baseline of this field depends mainly on two major methods, passive and active process [2,[7][8][9][10][11]. The former relates directly to the nature of tumor capillary vessels, and the later depends on the interaction mechanism with cancer cells.…”

“…This method was divided into two major groups: targeting that depends on the direct interaction between carrier and cancer cells and that, which uses physical signals as the main part of the system [10,11]. In the active interaction process, carrier molecules have been designed to interact with cancer cells directly by either an antigen-antibody reaction or ligand-receptor pathway [2,12]. Folate receptors, for instance, may be highly expressed in cancer cells compared with normal tissue due to high folate required for tumor growth.…”

“…However, due to the lower selectivity of anticancer drugs to differentiate between malignant and normal cells, serious adverse effects appear as a major issue. Therefore, targeting cancer cells has emerged as a priority of researchers to develop a safe and selective method for delivering the drug directly into the malignant cells [2]. Recently, several studies have attempted to create an ideal method for drug delivery with higher safety and efficacy.…”

<p>Hypoxia-Targeting Multifunctional Nanoparticles for Sensitized Chemotherapy and Phototherapy in Head and Neck Squamous Cell Carcinoma</p>

“…Nanotechnology-based drug delivery systems (DDSs) are a research hotspot in recent years, [14][15][16] which can carry multiple drugs and transfer them into tumors by passive targeting due to damaged or immature tumor vessels, a phenomenon named the enhanced permeability and retention (EPR) effect. 17,18 However, efforts are still being made to improve active targeting by fully exploring the tumor features. [19][20][21][22] Currently, the most commonly used active targeting ligands include transferrin, 23 folic acid, 24 and Arg-Gly-Asp.…”

The Role of Glucose Transporter 1 in Drug Delivery: Transporter, Receptor and/or Signaling Component

“…Moieties on the nanoparticle serve as a ligand that targets the receptors on the cancer tissue [3]. More than fifteen molecules have been targeted in order to deliver chemotherapeutic drugs in cancer therapy, including transferrin receptors, integrins, growth factor receptors, cluster of differentiation (CD) markers, glucose transporters (GLUTs), and asialoglycoprotein receptors [4]. Glucose and other monosaccharide are conjugated to nanocarrier for targeting GLUTs and asialoglycoprotein receptor.…”