Specific Drug Delivery to Cancer Cells with Double-Imprinted Nanoparticles against Epidermal Growth Factor Receptor

Abstract

Epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, is over-expressed in many tumors, including almost half of triple-negative breast cancers. The latter belong to a very-aggressive and drug-resistant form of malignancy. Although humanized anti-EGFR antibodies can work efficiently against these cancers both as monotherapy and in combination with genotoxic drugs, instability and high production costs are some of their known drawbacks in clinical use. In addition, the development of antibodies to target membrane proteins is a very challenging task. Accordingly, the main focus of the present work is the design of supramolecular agents for the targeting of membrane proteins in cancer cells and, hence, more-specific drug delivery. These were produced using a novel double-imprinting approach based on the solid-phase method for preparation of molecularly imprinted polymer nanoparticles (nanoMIPs), which were loaded with doxorubicin and targeted toward a linear epitope of EGFR. Additionally, upon binding, doxorubicin-loaded anti-EGFR nanoMIPs elicited cytotoxicity and apoptosis only in those cells that over-expressed EGFR. Thus, this approach can provide a plausible alternative to conventional antibodies and sets up a new paradigm for the therapeutic application of this class of materials against clinically relevant targets. Furthermore, nanoMIPs can promote the development of cell imaging tools against difficult targets such as membrane proteins.

Chemical Antibody Mimics Inhibit Cadherin‐Mediated Cell–Cell Adhesion: A Promising Strategy for Cancer Therapy

“…A molar percentage ratio 2:5:8 of functional monomers comprising N ‐phenylacrylamide (PAA), 4‐acrylamidophenyl (amino)‐methaniminium acetate (AB, benzamidine‐based monomer), and N‐tert ‐butylacrylamide (TBAM), to enable π–π, electrostatic, and hydrophobic interactions, respectively, with the template, was used. N ‐isopropylacrylamide (NIPAM) functional monomer was added at a high molar ratio of minimum 80 % to endow the polymers with thermoresponsiveness and facilitate their elution from the solid support.…”

“…MIPs were first described in the 1970–80s, but it is only in the past few years that their potential in cell biology research and nanomedicine applications has emerged. Indeed MIPs templated with monosaccharides, peptides, and proteins have been shown to interact with cells and even regulate cell behaviors, thanks to the production of nanosized biocompatible polymers with high affinity. In this work, we took advantage of the exposed N‐terminal part of cadherins (Supporting Information, Figure S2) to create a MIP that selectively recognizes a relevant epitope in classical type I cadherins.…”

Inhibition of HER2‐Positive Breast Cancer Growth by Blocking the HER2 Signaling Pathway with HER2‐Glycan‐Imprinted Nanoparticles

“…Compared with antibodies, MIPs have advantages such as easy preparation, chemically stable, and low cost. MIPs have found important applications in many areas, such as separation, sensing, drug delivery, disease diagnosis, and photothermal therapy of cancer . Clearly, the use of MIPs as cancer therapeutic agents is still at a very early stage and further evidence of inhibiting cancer signaling pathways by MIPs are essential to promote the development of MIPs for cancer therapy.…”

Inhibition of HER2‐Positive Breast Cancer Growth by Blocking the HER2 Signaling Pathway with HER2‐Glycan‐Imprinted Nanoparticles

“…[15] Compared with antibodies,M IPs have advantages such as easy preparation, chemically stable,and low cost. MIPs have found important applications in many areas,s uch as separation, [16] sensing, [17] drug delivery, [18] disease diagnosis, [19] and photothermal therapy of cancer. [20] Clearly,the use of MIPs as cancer therapeutic agents is still at av ery early stage and further evidence of inhibiting cancer signaling pathways by MIPs are essential to promote the development of MIPs for cancer therapy.…”