The in vivo fate and targeting engineering of crossover vesicle-based gene delivery system.

Phage display is an effective and powerful technique that provides a route to discovery unique peptides targeting to tumor cells. Specifically binding peptides are considered as the valuable target directing molecule fragments with potential efficiency to improve the current tumor clinic, and offer new approaches for tumor prevention, diagnosis and treatment. We focus on the recent advances in the isolation of tumor-targeting peptides by biopanning methods, with particular emphasis on molecular imaging, and pharmaceutical targeting therapy.

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Application of Phage-Displayed Peptides in Tumor Imaging Diagnosis and Targeting Therapy.

The aim of this study was to propose a new dual-modality nanoprobe for positron emission tomography/magnetic resonance imaging (PET/MRI) for the early diagnosis of breast cancer. For synthesis of the nanoprobe, polyethylene glycol-coated ultra-small superparamagnetic iron-oxide nanoparticles (USPION) armed with NODA-GA chelate and grafted with bombesin (BBN) were radiolabeled with 68Ga. After characterization, in vitro studies to evaluate the cell binding affinity of the nanoprobe were done by performing Perl's Prussian blue cell staining and MRI imaging. Finally, for in vivo studies, magnetic resonance images were taken in SCID mice bearing breast cancer tumor pre- and post-injection, and a multimodal nanoScan PET/computed tomography was used to perform preclinical imaging of the radiolabeled nanoparticles. Afterwards, a biodistribution study was done on sacrificed mice. The results showed that the highest r1 and r2 values were measured for USPIONs at 20 and 60 MHz, respectively. From the in vitro studies, the optical density of the cells after incubation increased with the increase of the iron concentration and the duration of incubation. However, the T2 values decreased when the iron concentration increased. Furthermore, from in vivo studies, the T2 and signal intensity decreased during the elapsed time post-injection in the tumor area. In this study, the in vitro studies showed that the affinity of cancer cells to nanoprobe increases meaningfully after conjugation with BBN, and also by increasing the duration of incubation and the iron concentration. Meanwhile, the in vivo results confirmed that the blood clearance of the nanoprobe happened during the first 120 min post-injection of the radiolabeled nanoprobe and also confirmed the targeting ability of that to a gastrin-releasing peptide receptor positive tumor.

https://iopscience.iop.org/article/10.1088/1361-6528/ab4446/pdf

Preliminary studies of 68Ga-NODA-USPION-BBN as a dual-modality contrast agent for use in positron emission tomography/magnetic resonance imaging.

Improved delivery system for celastrol-loaded magnetic Fe3O4/α-Fe2O3 heterogeneous nanorods: HIF-1α-related apoptotic effects on SMMC-7721 cell.

Breast cancer is a popular fatal malignant tumor for women with high of rates incidence and mortality. Development of the new approaches for breast cancer targeted diagnosis and chemotherapy is emergently needed by the current clinical practice, the important first step is finding a breast cancer specifically binding molecule or fragment as early clinical indicators. By a phage-displayed peptide library, a 12-mer peptide, CSB1 was screened out using MCF-7 cells as the target. The consequently results under immunofluorescence and laser scanning confocal microscope (LSCM) indicated that CSB1 bound MCF-7 cells and breast cancer tissues specifically and sensitively with high affinity. Bioinformatics analysis suggested that the peptide CSB1 targets the 5-Lipoxygenase-Activating Protein (FLAP), which has been implicated in breast cancer progression and prognosis. The peptide, CSB1 is of the potential as a candidate to be used for developing the new approaches of molecular imaging detection and targeting chemotherapy of breast cancer in the future.

Screening and identification of a specific peptide binding to breast cancer cells from a phage-displayed peptide library

'Targeting peptides' have demonstrated their value in diagnostic imaging and therapy and novel peptide probes specific to cervical cancer were developed. In the M13KE phage dodecapeptide (12-mer) peptide library, the phage clone S7 showed the best binding to the cancer cells as confirmed by immunofluorescence and flow cytometry assays, and was selected for continued studies. Its binding peptide, CSP3, was synthesized from the sequence of S7's 12-mer at the N-terminus of the minor coat protein pIII of this M13KE phage vector. The peptide's binding was analyzed by the same assays used for S7. It was also assessed using competitive inhibition and binding to a tissue chip. The results demonstrated that the CSP3 peptide bound to cervical carcinoma cells with high sensitivity and specificity. The positive results indicated that the peptide CSP3, conjugated with nanomaterials and chemotherapeutics, may be developed as a targeting vehicle for therapeutic drug delivery against cervical cancer, especially cervical cancer with multiple drug resistance. For this aim, we prepared a CSP3 conjugated liposome drug delivery system containing doxorubicin (DOX) and microRNA101 (miR101) expression plasmids (CSP3-Lipo-DOX-miR101), and the primary result showed that the system demonstrated significantly enhanced cytotoxicity to SiHa cells and DOX resistant SiHa cells, SiHa/ADR. Our results showed that CSP3 is a cervical cancer targeting 12aa peptide with high specificity and sensitivity, and the CSP3 conjugated drug delivery system, CSP3-Lipo-DOX-miR101 has promising potential for development as an efficient drug system for the therapy of cervical cancer.

https://iopscience.iop.org/article/10.1088/1361-6528/aaf3f8/pdf

Development of a novel drug targeting delivery system for cervical cancer therapy

The invention relates to a polypeptide specifically bound with a human cervical cancer cell and application thereof. The amino acid sequence of the polypeptide is QQLKDPWHSTPY. According to the application, the polypeptide specifically bound with the human cervical cancer cell SiHa is specifically bound with the human cervical cancer. The cervical cancer targeted polypeptide obtained through screening and preliminary identification has the obvious cervical cancer cell binding specificity, and can be used for developing a cervical cancer early-stage targeted diagnosis reagent and an efficient low-toxicity targeted therapy medicine.

Polypeptide specifically bound with human cervical cancer cell and application thereof

The invention relates to human ovarian carcinoma cell SKOV3 specifically binding polypeptide and an application thereof, wherein the amino acid sequence of the polypeptide is ASPLAPWSSVGP and the application is specific combination with human ovarian carcinoma cells by means of the human ovarian carcinoma cell SKOV3 specifically binding polypeptide. The ovarian carcinoma cell targeted polypeptide, which is obtained through screening and initial verification, has significant specificity of combination with the human ovarian carcinoma cells and can be used for researching a target diagnosis reagent for ovarian carcinoma in early stage and delivery of high-effect and low-toxic target medicines.

Human ovarian carcinoma cell specifically binding polypeptide and application thereof

The invention relates to a liposome and application thereof The liposome provided by the invention comprises a liposome preparation material, an anti-cancer medicine and a nucleic acid molecule, wherein the nucleic acid molecule has the effect of inverting the drug resistance of cancer cells on the coated anti-cancer medicine The liposome is used as a medicine carrier and the nucleic acid molecule and the anti-cancer medicine are covered with the liposome, so that a liposome medicine system which has a killing ability on the cancer cells and has the effects of inverting the drug resistance of the cancer cells on the coated anti-cancer medicine is formed According to the system, the liposome easily enters the cells, the anti-cancer medicine has the very strong cell killing ability and the nucleic acid molecule has the drug resistance inverting effect of the anti-cancer medicine, so that the liposome can be used in the aspects in the future that (1) anti-cancer medicine chemotherapy of cancer patients; (2) chemotherapy of cancer patients with drug resistance on doxorubicin; and (3) great improvement of the curative effect of the anti-cancer medicine and reduction of low chemotherapy effect and recurring caused by the drug resistance, and improvement of an existing bottleneck problem of the chemotherapy of the cancer patients

Ma Ni

Papers

Development of a novel drug targeting delivery system for cervical cancer therapy

Polypeptide specifically bound with human cervical cancer cell and application thereof

Human ovarian carcinoma cell specifically binding polypeptide and application thereof

Liposome and application thereof