Search

Late detection, peritoneal dissemination, chemoresistance and weak response to targeted therapeutics lead to high mortality in ovarian cancer. More efficient and specific tumor imaging and therapeutic agents are needed to improve the resection rate of surgery and to eliminate residual disease. The expression patterns of follicle-stimulating hormone (FSH) receptor make it a suitable target for ovarian cancer. Here, we report a strategy to develop an organic near-infrared probe for FSH receptor-targeted tumor imaging and photothermal therapy. The FSH-Rh760 probe was conjugated from the Rh760 fluorophore with the FSH β subunit 33–53 peptide. FSH-Rh760 specifically distinguished peritoneal metastatic ovarian cancerous foci from surrounding normal tissues with a high tumor-to-background ratio. The fluorescence signals in tumors peaked at 2 h and were cleared at 120 h postinjection. FSH-Rh760 treatment rapidly increased the abdomen temperature of mice up to ∼43 °C upon exposure to a near-infrared laser and effectively suppressed peritoneal tumor growth with tumor specificity. No significant systemic toxicities were observed. This study demonstrates the targeting ability and biocompatibility of FSH receptor-targeted theranostics and highlights its potential for clinical application in imaging-guided precision tumor resection and photothermal therapy to eliminate cancer lesions intraoperatively and postoperatively.

Commercial X-ray computed tomography (CT) contrast agents (CAs) are not appropriate for multicolor CT imaging and are limited due to a lack of tumor targeting. In this contribution, to favor the combination of high Z elements like bismuth and iodine for a broad range of X-ray photon energy, BiOI nanoparticles (NPs) are synthesized with hyaluronic acid (HA) coating to target the tumor cells with CD44 overexpression. The crystal structure of BiOI NPs is determined by X-ray powder diffraction, and the size of NPs is determined by a transmission electron microscope at about 14 ± 3 nm. The dynamic diameter of the NPs (DLS) in PBS buffer was measured at about 100 nm. Fourier transform infrared spectroscopy and thermal gravimetric analysis confirm the coating of BiOI NPs with HA. The stability of the NPs was also investigated via UV-vis spectroscopy. The immunocytochemistry process is performed to investigate the targeting ability of synthesized NPs on the human colon cancer cells with CD44 antigen. Finally, the X-ray attenuation of prepared HA-coated BiOI NPs is higher than Iohexol as the commercially available iodinated contrasting agent at the same concentrations, which can be administrated at much lower doses to achieve similar contrast to Iohexol., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Fluorescence imaging is an indispensable method for studying biological processes non-invasively in cells and transparent organisms. Extension into the shortwave infrared (SWIR, 1000-2000 nm) region of the electromagnetic spectrum has allowed for imaging in mammals with unprecedented depth and resolution for optical imaging. In this review, we summarize recent advances in imaging technologies, dye scaffold modifications, and incorporation of these dyes into probes for SWIR imaging in mice. Finally, we offer an outlook on the future of SWIR detection in the field of chemical biology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Multiple Myeloma, the second most prevalent hematologic malignancy, yet lacks an established curative therapy. However, overall response rate to modern four-drug regimens approaches 100%. Major efforts have thus focused on the measurement of minute quantities of residual disease (minimal residual disease or MRD) for prognostic metrics and therapeutic response evaluation. Currently, MRD is assessed by flow cytometry or by next generation sequencing to track tumor-specific immunoglobulin V(D)J rearrangements. These bone marrow-based methods can reach sensitivity thresholds of the identification of one neoplastic cell in 1,000,000 (10 -6 ). New technologies are being developed to be used alone or in conjunction with established methods, including peripheral blood-based assays, mass spectrometry, and targeted imaging. Data is also building for MRD as a surrogate endpoint for overall survival. Here, we will address the currently utilized MRD assays, challenges in validation across labs and clinical trials, techniques in development, and future directions for successful clinical application of MRD in multiple myeloma., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Fluorescent organic dots (O-dots) recently have emerged as a new class of promising contrast reagents for two-photon fluorescence (TPF) imaging. However, most of these developed two-photon absorption (TPA) O-dots have no tumor-targeting group, which hampers their wide application for targeted tumor imaging. Herein, we fabricated Sgc8c aptamer-mediated TPA O-dots as a proof-of-concept of the sensing platform for targeted imaging in live cells or deep tissues. The O-dots composed of trans-4-[p-(N, N-diethylamino)styryl]-4'-(dimethyl amino) stilbene (DEAS) emerged as TPA organic emissive cores and encapsulation by using poly (methyl methacrylate-co-methacrylic acid) (PMMA-co-MAA) as polymeric encapsulating matrix to form DEAS/PMMA-co-MAA O-dots via a co-precipitation strategy. The obtained O-dots enabled an extremely high TPA absorption cross-section, bright two-photon fluorescence (excitation at 720 nm; emission at 412 nm and 434 nm), excellent cell-permeability and high penetration depth. Sgc8c aptamer, as a protein tyrosine kinase-7 (PTK7) receptor-targetable ligand, was further anchored on the surface of O-dots to obtain DEAS/PMMA-co-MAA@Sgc8c nanoprobes by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)-mediated coupling reaction. Guided by Sgc8c aptamer, DEAS/PMMA-co-MAA@Sgc8c nanoprobes could be rapidly internalized into target acute lymphoblastic leukemia cells (CEM) cells with high specificity and great efficiency. It was also performed that two-photon images of TPA nanoprobes exhibited high two-photon brightness not only in target CEM cells, but also in mouse liver tissue slices even a depth of up to 210 μm. In our perception, it is highly promising that this nanoprobe provides a valuable tool for in vivo targeted imaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Fluorescence imaging via carbon dots (CDs) has found multifarious applications in the biomedical sciences including biosensing, cancer cell bioimaging, drug delivery and tracking therapeutic response. Presently, the latest generation of fluorescence CDs known as green-CDs has attracted ever-increasing attention due to the use of natural sources, low-cost synthesis, nanoscale size, promising biocompatibility, superior photoluminescence, and ease of functionalization for versatile applications, which in turn could have higher priority over the traditional toxic fluorescent agents. In this review, we aim to have a new insight into the engineering green-CDs and their physicochemical properties. Moreover, we discuss the possible applications of green-CDs in self and active targeting, therapeutics delivery, and finally their promising future in cancer theranostics., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Gastric cancer (GC) is associated with high morbidity and mortality rates worldwide. Poorly differentiated GC predicts a poor prognosis and is related to patients' response to chemotherapy and targeted therapy. Therefore, it is very important to accurately evaluate the tumour differentiation status for the treatment of poorly differentiated GC. To develop a molecular probe to analyse poorly differentiated GC, we selected aptamers against poorly differentiated GC by subtractive Cell-SELEX using the poorly differentiated GC cell line BGC-823 as the target and the moderately differentiated GC cell line SGC-7901 as the negative control. After 15 rounds of selection, aptamer PDGC21 exhibited the highest affinity, and the K d value of the truncated aptamer PDGC21-T was 35.2 ± 1.1 nM. Aptamer PDGC21-T not only specifically bound to the target cells but also bound to other poorly differentiated GC cells. When combined with fluorescent nanoparticle quantum dots (QDs), the PDGC21-T-QD probe could distinguish poorly differentiated GC cells in mixed culture cells and clinical specimens. Furthermore, in a tissue microarray containing 15 cases from patients, there was a higher positive rate in GC tissues compared with adjacent normal tissues; in poorly differentiated tissues, in particular, the fluorescence signal was significantly higher than that in well/moderately differentiated tissues. Therefore, aptamer PDGC21-T holds great potential for use as a molecular imaging probe for the detection of poorly differentiated GC, which is of great significance for diagnosis and treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Lactosylated albumin is currently used as a radiopharmaceutical agent to image the liver asialoglycoprotein receptors and quantify hepatic liver function in various diseases. A lactosylated protein (LACTAL) conjugate showed excellent liver uptake compared to non-lactosylated protein and a high signal to noise ratio, based on the biodistribution in mice using 99m Tc-scintigraphy. However, in the laboratory, it is useful to have a method that can be used in daily practice to quantify cellular targeting or biodistribution. We propose a methodology from synthesis validation to pre-clinical demonstration and introduce a new practical detector (LACTAL.Eu) of the LACTAL molecule in biological media. We confirmed the purity and colloidal stability of the sample through physical analytical techniques, then showed the absence of in vitro toxicity of the agent and demonstrated in vitro targeting. Taking advantage of the fluorescence decay of the lanthanide, we performed measurements directly on the cell media without any further treatment. Finally, biodistribution in mice was confirmed by ex vivo measurements., (Copyright © 2019 Elsevier Inc. All rights reserved.)

It is important to obtain the targeted nanocarriers during cancer treatment. Herein, mannosylated liposomes encapsulating carbon dots (CDs) are provided for targeted recognition of liver cancer HepG2 cells, which is based on the specific interaction between D-mannose and glycoprotein on the surface of HepG2 cells. CDs were prepared by hydrothermal method. Then, they were encapsulated into liposomes by hydrophobic force. The encapsulation of CDs into liposomes increases their stability and fluorescence intensity. Furthermore, D-mannose can also be inserted into liposomes by the aldehyde amine reaction between aldehyde groups of mannose molecules and amino groups of liposomes. The obtained D-mannose-CDs-liposomes (Man-CDs-liposomes) exhibit selectively tracking and efficiently labelling for cancer cells. The work highlights the potential application of CDs for bioimaging and diagnostic., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Nanoparticle-based drug delivery systems have drawn a great deal of attention for their opportunities to improve cancer treatments over intrinsic limits of conventional cancer therapies. Herein, we developed the polypeptide-modified gold nanoclusters (GNCs)-based nanoprobes for tumor-targeted near-infrared fluorescence imaging and chemo-photodynamic therapy. The nanoprobes comprise of tetra-functional components: i) polyethylene glycol (PEG) shell for long blood circulation and better biocompatibility; ii) MMP2 polypeptide (CPLGVRGRGDS) for tumor targeting; iii) cis-aconitic anhydride-modified doxorubicin (CAD) for pH-sensitive drug release; iv) photosensitizer chlorin e6 (Ce6) for photodynamic therapy and fluorescence imaging. The in vitro results demonstrated that the as-synthesized nanoprobes could be efficiently internalized into A549 cells and then significantly enhance the mortality of cancer cells compared with free Ce6 and doxorubicin. For in vivo tests, the nanoprobes showed excellent tumor targeting ability, long blood circulation time, and could remarkably inhibit the growth of tumor. Our results will help to advance the design of combination strategies to enhance the efficacy of imaging-guided cancer therapy., Statement of Significance: The as-prepared CDGM NPs could accumulate into the tumor tissue with the enhanced permeability and retention (EPR) effect as well as the active tumor targeting ability from the MMP2 polypeptides. With the acid-sensitive linker, the doxorubicin (DOX) would be released from the synthesized nanoparticles after exposing to the acid tumor microenvironment. The CDGM NPs exhibit excellent tumor targeting ability and could remarkably suppress the growth of tumor compared with free Ce6 and DOX., (Copyright © 2017. Published by Elsevier Ltd.)