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Guiding nanomaterials to tumors for breast cancer precision medicine: from tumor-targeting small-molecule discovery to targeted nanodrug delivery.

ABSTRACT: Precision medicine emphasizes patient-specific formulation for treatment of diseases, especially cancer. However, in targeted cancer treatment, because the expression level of tumor receptors in each patient varies even for the same type of cancer, the ligand/receptor-mediated approach does not seem promising for precision medicine. In this work, we demonstrated our strategy of using a phage display technique for breast cancer precision medicine. Using in vivo biopanning, we first selected an MCF-7 breast tumor-targeting peptide, then tested the effectiveness of the as-selected peptide in tumor homing and finally conjugated the peptide to a model photothermal drug, namely, gold nanorods, to achieve enhanced cancer killing efficacy. The peptides identified by the phage display technique can guide the drug to the tumors without the need to know the exact receptors on the tumor. This approach requires significantly less effort to explore patient-specific targeting molecules for precision medicine.

SUBMITTER: Qu X

PROVIDER: S-EPMC5898397 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Guiding nanomaterials to tumors for breast cancer precision medicine: from tumor-targeting small-molecule discovery to targeted nanodrug delivery.

Qu Xuewei X Qiu Penghe P Zhu Ye Y Yang Mingying M Mao Chuanbin C

NPG Asia materials 20171208

Precision medicine emphasizes patient-specific formulation for treatment of diseases, especially cancer. However, in targeted cancer treatment, because the expression level of tumor receptors in each patient varies even for the same type of cancer, the ligand/receptor-mediated approach does not seem promising for precision medicine. In this work, we demonstrated our strategy of using a phage display technique for breast cancer precision medicine. Using <i>in vivo</i> biopanning, we first selecte ...[more]

PMID: 29657602

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Project description:The polygenetic nature of most cancers emphasizes the necessity of cancer therapies that target multiple essential signaling pathways. However, there is a significant paucity of targeting ligands with multi-specificities for targeted delivery of biomaterials. To address this unmet need, we generated a tetraspecific targeting ligand that recognizes four different cancer biomarkers, including VEGFR2, ?v?3 integrin, EGFR, and HER2 receptors, which have been implicated in numerous malignant tumors. The tetraspecific targeting ligand was constructed by sequentially connecting four targeting ligand subunits via flexible linkers, yielding a fusion protein that can be highly expressed in Escherichia coli and readily purified to near homogeneity. Surface Plasmon Resonance (SPR), Bio-Layer Interferometry (BLI) studies and extensive cellular binding analyses indicated that all the targeting ligand subunits in the tetraspecific fusion protein recognized their target receptors proximately to the corresponding monospecific ligands. The resulting tetraspecific targeting ligand was applied for the delivery of nanomaterials such as gold nanoparticles (AuNPs) for targeted hyperthermic killing of various cancer cell lines with biomarkers of interest expressed. We demonstrate that the tetraspecific ligand can be facilely introduced on the surface of AuNPs and efficient target-dependent killing of cancer cells can be achieved only when the AuNPs are conjugated with the tetraspecific ligand. Significantly, the tetraspecific ligand simultaneously interacts with more than one receptors, such as EGFR and HER2 receptors, when they are expressed on the surface of the same cell, as demonstrated by in vitro binding assays and cell binding analyses. Our results demonstrate that the tetraspecific ligand, through multivalency and synergistic binding, can be readily used to generate various 'smart' biomaterials with greatly broadened tumor targeting range for simultaneous targeting of multiple signaling pathways on many different cancer types.

Dataset Information

Guiding nanomaterials to tumors for breast cancer precision medicine: from tumor-targeting small-molecule discovery to targeted nanodrug delivery.

Publications

Guiding nanomaterials to tumors for breast cancer precision medicine: from tumor-targeting small-molecule discovery to targeted nanodrug delivery.

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