Mucin-1 aptamer-armed superparamagnetic iron oxide nanoparticles for targeted delivery of doxorubicin to breast cancer cells

Introduction: Superparamagnetic iron oxide nanoparticles (SPIONs) can be functionalized with various agents (e.g., targeting and therapeutic agents) and used for targeted imaging/therapy of cancer. In the present study, we engineered doxorubicin (DOX)-conjugated anti-mucin-1 (MUC-1) aptamer (Ap)-armed PEGylated SPIONs for targeted delivery of DOX molecules to the breast cancer MCF-7 cells. Methods:The SPIONs were synthesized using the thermal decomposition method and modified by polyethylene glycol (PEG) to maximize their biocompatibility and minimize any undesired cytotoxicity effects. Subsequently, DOX molecules were loaded onto the SPIONs, which were further armed with amine-modified MUC-1 aptamer by EDC/NHS chemistry. Results: The morphologic and size analyses of nanoparticles (NPs) by transmission electron microscopy (TEM) and dynamic light scattering (DLS) revealed spherical and monodisperse MNPs with a size range of 5-64 nm. The FT-IR spectrophotometry and 1HNMR analysis confirmed the surface modification of NPs. The cytotoxicity assay of the aptamer-armed MNPs exhibited a higher death rate in the MUC-1 over-expressing MCF-7 cells as compared to the MUC-1 under-expressing MDA-MB-231 cells. The flow cytometry analysis of the engineered Ap-armed SPIONs revealed a higher uptake as compared to the SPIONs alone. Conclusion: Based on our findings, the anti-MUC-1 Ap-armed PEGylated SPIONs loaded with DOX molecules could serve as an effective multifunctional theranostics for simultaneous detection and eradication of MUC-1-positive breast cancer cells

Hydrogels for ocular drug delivery and tissue engineering

Hydrogels, as crosslinked polymeric three dimensional networks, possess unique structure and behavior in response to the internal and/or external stimuli. As a result, they offer great prospective applications in drug delivery, cell therapy and human tissue engineering. Here, we highlight the potential of hydrogels in prolonged intraocular drug delivery and ocular surface therapy using stem cells incorporated hydrogels

Theranostic Advances in Breast Cancer in Nuclear Medicine

The implication of ‘theranostic’ refers to targeting an identical receptor for diagnostic and therapeutic purposes, by the same radioligand, simultaneously or separately. In regard to extensive efforts, many considerable theranostic tracers have been developed in recent years. Emerging evidence strongly demonstrates the tendency of nuclear medicine towards therapies based on a diagnosis. This review is focused on the examples of targeted radiopharmaceuticals for the imaging and therapy of breast cancer

Radiolabeled theranostics: magnetic and gold nanoparticles

Introduction: Growing advances in nanotechnology have facilitated the applications of newly emerged nanomaterials in the field of biomedical/pharmaceutical sciences. Following this trend, the multifunctional nanoparticles (NPs) play a significant role in development of advanced drug delivery systems (DDSs) such as diapeutics/theranostics used for simultaneous diagnosis and therapy. Multifunctional radiolabeled NPs with capability of detecting, visualizing and destroying diseased cells with least side effects have been considered as an emerging filed in presentation of the best choice in solving the therapeutic problems. Functionalized magnetic and gold NPs (MNPs and GNPs, respectively) have produced the potential of nanoparticles as sensitive multifunctional probes for molecular imaging, photothermal therapy and drug delivery and targeting. Methods: In this study, we review the most recent works on the improvement of various techniques for development of radiolabeled magnetic and gold nanoprobes, and discuss the methods for targeted imaging and therapies. Results: The receptor-specific radiopharmaceuticals have been developed to localized radiotherapy in disease sites. Application of advanced multimodal imaging methods and related modality imaging agents labeled with various radioisotopes (e.g., 125I, 111In, 64Cu, 68Ga, 99mTc) and MNPs/GNPs have significant effects on treatment and prognosis of cancer therapy. In addition, the surface modification with biocompatible polymer such as polyethylene glycol (PEG) have resulted in development of stealth NPs that can evade the opsonization and immune clearance. These long-circulating agents can be decorated with homing agents as well as radioisotopes for targeted imaging and therapy purposes. Conclusion: The modified MNPs or GNPs have wide applications in concurrent diagnosis and therapy of various malignancies. Once armed with radioisotopes, these nanosystems (NSs) can be exploited for combined multimodality imaging with photothermal/photodynamic therapy while delivering the loaded drugs or genes to the targeted cells/tissues. These NSs will be a game changer in combating various cancers

Radiosynthesis and evaluation of ytterbium-175 labeled bleomycin as therepeutic agent

ABSTRACT Introduction: Bleomycins are DNA-binding biomolecules, which can be used as targeted therapy carriers when labeled with particle-emitters such as Yb-175. In this work the development of Yb-175 bleomycin

Preparation and Quality Control of 68Ga-Citrate for PET Applications

Objective(s): In nuclear medicine studies, gallium-68 (68Ga) citrate has been recently known as a suitable infection agent in positron emission tomography (PET). In this study, by applying an in-house produced 68Ge/68Ga generator, a simple technique for the synthesis and quality control of 68Ga-citrate was introduced; followed by preliminary animal studies. Methods: 68GaCl3 eluted from the generator was studied in terms of quality control factors including radiochemical purity (assessed by HPLC and RTLC), chemical purity (assessed by ICP-EOS), radionuclide purity (evaluated by HPGe), and breakthrough. 68Ga-citrate was prepared from eluted 68GaCl3 and sodium citrate under various reaction conditions. Stability of the complex was evaluated in human serum for 2 h at 370C, followed by biodistribution studies in rats for 120 min. Results: 68Ga-citrate was prepared with acceptable radiochemical purity (>97 ITLC and >98% HPLC), specific activity (4-6 GBq/mM), chemical purity (Sn, FeConclusion: This study demonstrated the possible in-house preparation and quality control of 68Ga-citrate, using a commercially available 68Ge/68Ga generator for PET imaging throughout the country

Radiosynthesis and biodistribution studies of [62Zn/62Cu]-plerixafor complex as a novel in vivo PET generator for chemokine receptor imaging

In order to develop a possible C-X-C chemokine receptor type 4 (CXCR4) imaging agent for oncological scintigraphy, [62Zn]labeled 1,1'-[1,4-phenylenebis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane ([62Zn]-AMD3100) was prepared using in-house made [62Zn]ZnCl2 and AMD-3100 for 1h at 50 °C (radiochemical purity: >97 % ITLC, >96 % HPLC, specific activity: 20-22 GBq/mmol) in acetate buffer. The complex showed highly hydrophilic properties (log P = -1.114). Stability of the complex was checked in presence of human serum (37 °C) and in final formulation for 1 day. The biodistribution of the labeled compound in vital organs of wild-type Sprague-Dawdley rats were determined and compared with that of free Zn2+ cation up to 6h. Co-incidence imaging of the complex was consistent with the distribution data up to 3h. The complex can be a possible in vivo generator compound for PET imaging in CXCR4 positive tumors

Synthesis and Evaluation of [67Ga]-AMD3100: A Novel Imaging Agent for Targeting the Chemokine Receptor CXCR4

In order to develop a possible C-X-C chemokine receptor type 4 (CXCR4) imaging agent for oncological scintigraphy, [67Ga]-labeled 1,1′-[1,4-Phenylene-bis(methylene)]bis(1,4,8,11-tetraazacyclotetradecane) ([67Ga]-AMD3100) was prepared by using [67Ga]GaCl3 and AMD-3100 for 2 h at 50 °C (radiochemical purity: >95% ITLC, >99% HPLC, specific activity: 1800–2000 TBq/mmol) in acetate buffer. The stability of the complex was checked in the presence of human serum (37 °C) and in the final formulation for four days. The biodistribution of the labeled compound in the vital organs of wild type Sprague-Dawley rats was determined and compared with that of the free Ga3+ cation up to 48 h. Considering the spleen as the target organ, the best target:non target ratios were obtained 48 h post-injection (spleen:blood ratio; 14.5 and spleen:muscle ratio; 88.4). Initial SPECT images and biodistribution results in the wild type rats matched each other and demonstrated rapid washout of the tracer from the urinary tract. SPECT images in human breast carcinoma-bearing mice demonstrated a detectable tumor uptake in 48 h post-injection