Blocking the HER2 signaling pathway has been an effective strategy in the treatment of HER2-positive breast cancer.I tm ainly relies on the use of monoclonal antibodies and tyrosine-kinase inhibitors.H erein, we present an ew strategy,the nano molecularly imprinted polymer (nanoMIP). The nanoMIPs,imprinted using HER2 N-glycans,could bind almost all HER2 glycans and suppress the dimerization of HER2 with other HER family members,b locking the downstream signaling pathways,t herebyi nhibiting HER2 + breast cancer growth. In vitro experiments demonstrated that the nanoMIPs specifically targeted HER2 + cells and inhibited cell proliferation by 30 %. In vivo experiments indicated that the mean tumor volume of the nanoMIP-treated group was only about half of that of the non-treated groups.T his study provides not only an ew possibility to treat of HER2 + breast cancer but also new evidence to boost further development of nanoMIPs for cancer therapy.
Molecularly imprinted polymers (MIPs), which are synthesized in the presence of a template, have been widely used as antibody mimics for important applications. Through the combination with a highly sensitive detection scheme such as chemiluminescence and surface-enhanced Raman scattering (SERS), MIP-based sandwich assays have emerged as promising analytical tools for the detection of disease biomarkers. However, so far, MIPs have been used only as target-capturing probes, whereas labeling by other means was needed, which limits the application range. Herein, we present a new approach, called a dual MIP-based plasmonic immunosandwich assay (duMIP-PISA), for the specific and sensitive detection of protein biomarkers in complex biological samples. A C-terminal epitope-imprinted self-assembled gold nanoparticle monolayer-coated glass slide was prepared as a plasmonic substrate for the specific extraction of target protein, while N-terminal epitope-imprinted Raman-responsive Ag@SiO2 nanoparticles were prepared as nanotags for the specific labeling of captured protein. The formed MIP–protein–MIP sandwich-like complexes could produce a significantly enhanced SERS signal. The dual MIP-based recognitions ensured high specificity of the assay, while SERS detection provided ultrahigh sensitivity. The duMIP-PISA of neuron-specific enolase (NSE) in human serums was demonstrated, which permitted the differentiation of small cell lung cancer patients from healthy individuals. As compared to regular ELISA, the duMIP-PISA exhibited multiple merits including a simpler procedure, faster speed, lower sample volume requirement, and wider linear range. The approach well demonstrated the great potentials of MIPs and can be easily modified and extended to other protein biomarkers. Therefore, the duMIP-PISA approach holds great promise in many important applications such as disease diagnosis.
Prodrug and drug delivery systems are two effective strategies for improving the selectivity of chemotherapeutics. Molecularly imprinted polymers (MIPs) have emerged as promising carriers in targeted drug delivery for cancer treatment, but they have not yet been integrated with the prodrug strategy. Reported here is an MIP‐based smart prodrug delivery system for specific targeting, prolonged retention time, and tumor microenvironment‐triggered release. 5′‐Deoxy‐5‐fluorocytidine (DFCR) and sialic acid (SA) were used as a prodrug and a marker for tumor targeting, respectively. Their co‐imprinted nanoparticles were prepared as a smart carrier. Prodrug‐loaded MIP specifically and sustainably accumulated at the tumor site and then gradually released. Unlike conventional prodrug designs, which often require in‐liver bioconversion, this MIP‐based prodrug delivery is liver‐independent but tumor‐dependent. Thus, this study opens new access to the development of smart prodrug delivery nanoplatforms.
Blocking the HER2 signaling pathway has been an effective strategy in the treatment of HER2-positive breast cancer.I tm ainly relies on the use of monoclonal antibodies and tyrosine-kinase inhibitors.H erein, we present an ew strategy,the nano molecularly imprinted polymer (nanoMIP). The nanoMIPs,imprinted using HER2 N-glycans,could bind almost all HER2 glycans and suppress the dimerization of HER2 with other HER family members,b locking the downstream signaling pathways,t herebyi nhibiting HER2 + breast cancer growth. In vitro experiments demonstrated that the nanoMIPs specifically targeted HER2 + cells and inhibited cell proliferation by 30 %. In vivo experiments indicated that the mean tumor volume of the nanoMIP-treated group was only about half of that of the non-treated groups.T his study provides not only an ew possibility to treat of HER2 + breast cancer but also new evidence to boost further development of nanoMIPs for cancer therapy.
Circulating microRNAs (miRNAs) hold great value in the diagnostics of cancer diseases. Ultrasensitive detection schemes are essential for the determination of circulating miRNAs, due to the limited levels of miRNAs in human serum. To this end, surface enhanced Raman scattering (SERS), which relies on plasmonic nanomaterials to amplify the Raman signal, has evolved as a promising tool. However, plasmonic nanomaterials that allow for fast and ultrasensitive SERS detection are still much needed. Herein, we proposed a fast and ultrasensitive strategy for the determination of circulating miRNAs in human serum, called gold nanoparticle (AuNP)-decorated Ag@SiO 2 nanocomposite-based plasmonic affinity sandwich assay (PASA). We first theoretically verified the presence of multiple hot-spots around the nanocomposite and then experimentally demonstrated the improved detection sensitivity generated by the AuNP-decorated Ag@ SiO 2 nanocomposite. The PASA approach exhibited several significant advantages including ultrahigh sensitivity (the limit of quantification was 10 fM), fast speed (the total analysis time was only 3 h), and very low sample volume requirement (only 5 μL). Quantification of miR-21 in human serum was achieved by the method, which allowed for differentiation of a breast cancer patient from a healthy individual. The AuNP-decorated Ag@SiO 2 nanocomposite and the PASA method can be easily extended for other microRNAs and circulating tumor DNA. Therefore, the PASA method holds great promise for cancer diagnosis.
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