Molecularly Imprinted Polymer Nanoparticles: An Emerging Versatile Platform for Cancer Therapy

Abstract

Molecularly imprinted polymers (MIPs) are chemically synthesized affinity materials with tailor-made binding cavities complementary to the template molecules in shape, size, and functionality. Recently, engineering MIP-based nanomedicines to improve cancer therapy has become a rapidly growing field and future research direction. Because of the unique properties and functions of MIPs, MIP-based nanoparticles (nanoMIPs) are not only alternatives to current nanomaterials for cancer therapy, but also hold the potential to fill gaps associated with biological ligand-based nanomedicines, such as immunogenicity, stability, applicability, and economic viability. Here, we survey recent advances in the design and fabrication of nanoMIPs for cancer therapy and highlight their distinct features. In addition, how to use these features to achieve desired performance, including extended circulation, active targeting, controlled drug release and anti-tumor efficacy, is discussed and summarized. We expect that this minireview will inspire more advanced studies in MIP-based nanomedicines for cancer therapy.

Keywords: cancer therapy; drug delivery; molecular imprinting; nanoparticles.

Figure 1

a) Retention and b) half‐life of HSA‐imprinted nanogels (MIP‐NGs) and non‐molecularly imprinted nanogels (NIP‐NGs) in the blood stream (n=5). P values were calculated from a two‐tailed t‐test. ^[15] Reprinted with permission. Copyright 2017, Wiley‐VCH.

Figure 2

A) Images of human melanoma cells (green) and the fluorescent hVEGF epitope‐imprinted nanoprobes (red), demonstrating the ability of hVEGF epitope‐imprinted nanoprobes to localize cancer cells overexpressing hVEGF in zebrafish embryos. ^[9a] Reprinted with permission. Copyright 2017, American Chemical Society. B) FACS analysis and confocal microscopy of binding specificity for fluorescent EGFR epitope‐imprinted nanoparticles to two breast cancer cell lines expressing different levels of EGFR. SKBR‐3 cells express low amounts of EGFR while MDA‐MB‐468 cells express high amounts of EGFR, confirming the specific binding of EGFR epitope‐imprinted nanoparticles (green) to the target protein. ^[9b] Reprinted with permission. Copyright 2018, American Chemical Society.

Figure 3

In vivo nanoparticle distribution in a subcutaneous tumor‐bearing mice model at different time points and fluorescence images of major organs and tumors ex vivo at 24 h post‐injection. A) a. Conformational epitope of p32‐imprinted nanoparticles, b. conformational epitope of Lyp‐1 (a peptide ligand binding to the N‐terminal domain of p32) imprinted nanoparticles, c. non‐imprinted nanoparticles. ^[9c] Reprinted with permission. Copyright 2015, Wiley‐VCH. B) a. Conformational epitope of FRα‐imprinted nanoparticles, b. scrambled epitope of FRα‐imprinted nanoparticles, c. non‐imprinted nanoparticles. ^[9d] Reprinted with permission. Copyright 2017, Royal Society of Chemistry.

Figure 4

Confocal fluorescence imaging of HepG‐2 cells (A, a liver cancer cell line), L‐02 cells (B, an immortal normal liver cell line), MCF‐7 cells (C, a breast cancer cell line) and MCF‐10A cells (D, a non‐transformed normal breast cell line) after staining with different monosaccharide‐imprinted nanoparticles. Columns from left to right: SA‐, Fuc‐, and Man‐imprinted nanoparticles. The concentration of the nanoparticles was 200 μg mL⁻¹. ^[40] Reprinted with permission. Copyright 2016, Nature Publishing Group.

Figure 5

Strand‐intercalation model of adhesive binding by classical type I cadherins. The five ectodomains are represented as gray and green ovals, the different colors symbolize cadherins from opposite cell surfaces. Ca²⁺ ions are shown as yellow rhombi. A) Adhesive binding occurs via N‐terminal strand dimerization. The dimerization involves the insertion of Trp2 (fuchsia) from one cadherin into the hydrophobic pocket located in the EC1 of the partner cadherin. B) Molecularly imprinted polymer nanoparticles (MIP‐NPs) (magenta) targeting an N‐terminal epitope of cadherin, block Trp2 and abrogate cell–cell adhesion. ^[9f] Reprinted with permission. Copyright 2019, Wiley‐VCH.

Figure 6

Illustration of the principle of blocking the HER2 signaling pathway via HER2‐glycan‐imprinted nanoparticles. ^[9e] Reprinted with permission. Copyright 2019, Wiley‐VCH.