Targeted Mitochondrial Fluorescence Imaging-Guided Tumor Antimetabolic Therapy with the Imprinted Polymer Nanomedicine Capable of Specifically Recognizing Dihydrofolate Reductase

Abstract

As we all know, inhibiting the activity of dihydrofolate reductase (DHFR) has always been an effective strategy for folate antimetabolites to treat tumors. In the past, it mainly relied on chemical drugs. Here, we propose a new strategy, (3-propanecarboxyl)triphenylphosphonium bromide (CTPB)modified molecularly imprinted polymer nanomedicine (MIP-CTPB). MIP-CTPB prepared by imprinting the active center of DHFR can specifically bind to the active center to block the catalytic activity of DHFR, thereby inhibiting the synthesis of DNA and ultimately inhibiting the tumor growth. The modification of CTPB allows the nanomedicine to be targeted and enriched in mitochondria, where DHFR is abundant. The confocal laser imaging results show that MIP-CTPB can target mitochondria. Cytotoxicity experiments show that MIP-CTPB inhibits HeLa cell proliferation by 42.2%. In vivo experiments show that the tumor volume of the MIP-CTPB-treated group is only one-sixth of that of the untreated group. The fluorescent and paramagnetic properties of the nanomedicine enable targeted fluorescence imaging of mitochondria and T 2 -weighted magnetic resonance imaging of tumors. This research not only opens up a new direction for the application of molecular imprinting, but also provides a new idea for tumor antimetabolic therapy guided by targeted mitochondrial imaging.

Molecularly imprinted polymers (MIPs): emerging biomaterials for cancer theragnostic applications

“…Blocking the enzymatic activity of DHFR in tumor cells can inhibit DNA synthesis and ultimately lead to cell death. Qin et al proposed a new anti-metabolic therapy using molecularly imprinted NPs with an inhibitory effect on the enzymatic activity of DHFR to inhibit tumor growth [ 175 ]. MIP-(3-propanecarboxyl) triphenyl phosphonium bromide (CTPB) was prepared by imprinting the active center peptide of DHFR related to DNA metabolism, followed by modifying the mitochondrial targeting moiety (CTPB) on the surface of MIP for effective targeting of the mitochondria.…”

Molecularly Imprinted Nanomaterials with Stimuli Responsiveness for Applications in Biomedicine

“…Compared with traditional MIPs, MIP nanoparticles (MIP-NPs) have a good dispersion ability, a high surface-area-to-volume ratio, and easy elution of template molecules, as well as exhibit a high binding capacity, high selectivity, high affinity, and good water compatibility [ 18 ]. Therefore, the application fields of MIP-NPs have also expanded from separation and detection to biomedicine (bioimaging [ 19 , 20 , 21 , 22 ], cancer diagnosis [ 23 , 24 , 25 ], targeted drug delivery [ 26 , 27 ], controlled drug release [ 28 , 29 , 30 ], etc.). MIP-NPs are expected to become an attractive research tool for a wide range of studies in the biomedical field.…”

Coordinately Tethered Iron(III) Fluorescent Nanotheranostic Polymer Ascertaining Cancer Cell Mitochondria Destined Potential Chemotherapy and T1-Weighted MRI Competency

“…To date, significant numbers of works on polymer-based mitochondrial nanomedicines have been widely carried out for various types of chemotherapies. − The prime objective of these works is the successful targeting of the mitochondria with adequate delivery of the preferred gene, chemotherapeutic drugs, or PDT/PTT agents. This eventually lead to irreversible mitochondrial dysfunction followed by tumor reduction for potential cancer treatment. − Although considerable research progress has been observed in this field, there are a limited number of literature reports available on dual-imaging polymer-based mitochondrial theranostic systems. Therefore, integrated fluorescence and magnetic resonance imaging-guided polymer-based mitochondrial nanomedicines have been preferentially explored in this study.…”