Specific Drug Delivery to Cancer Cells with Double-Imprinted Nanoparticles against Epidermal Growth Factor Receptor
Francesco Canfarotta1, Larissa Lezina2, António Guerreiro1
1MIP Diagnostics Ltd ., Fielding Johnson Building , Leicester , LE1 7RH United Kingdom.
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.
Insights
Researchers developed novel molecularly imprinted polymer nanoparticles (nanoMIPs) that target epidermal growth factor receptor (EGFR) in cancer cells. These doxorubicin-loaded nanoMIPs offer a promising alternative to antibodies for targeted cancer therapy and imaging.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapeutics
Background:
- Epidermal growth factor receptor (EGFR) is over-expressed in aggressive, drug-resistant triple-negative breast cancers.
- Conventional anti-EGFR antibodies face challenges including instability, high cost, and difficulty targeting membrane proteins.
- There is a need for alternative agents for specific cancer cell targeting and drug delivery.
Purpose of the Study:
- To design and develop supramolecular agents for targeted delivery to membrane proteins on cancer cells.
- To create molecularly imprinted polymer nanoparticles (nanoMIPs) loaded with doxorubicin for EGFR targeting.
- To establish a novel therapeutic approach as an alternative to traditional antibodies.
Main Methods:
- Utilized a novel double-imprinting approach on a solid-phase method to create nanoMIPs.
- Engineered nanoMIPs to target a specific linear epitope of EGFR on cancer cells.
- Loaded nanoMIPs with the chemotherapeutic agent doxorubicin.
Main Results:
- Doxorubicin-loaded anti-EGFR nanoMIPs demonstrated targeted delivery and binding to EGFR-overexpressing cells.
- The nanoMIPs successfully elicited cytotoxicity and apoptosis specifically in cancer cells with EGFR over-expression.
- The approach showed specificity, impacting only cells with the target membrane protein.
Conclusions:
- The developed nanoMIPs offer a viable alternative to conventional antibodies for targeting membrane proteins like EGFR.
- This technology presents a new paradigm for therapeutic applications of supramolecular agents in cancer treatment.
- NanoMIPs hold potential for developing advanced cell imaging tools against challenging targets such as membrane proteins.
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