Theranostic Agents For Cancer Treatment Research Articles

Enhanced Tumor Targeting of Radiolabeled Mouse/Human Chimeric Anti-Tn Antibody in Losartan-Treated Mice Bearing Tn-Expressing Lung Tumors.

Aim: ChiTn, a mouse/human chimeric anti-Tn monoclonal antibody, was radiolabeled with iodine-131 (131I) and technetium-99m (99mTc) to assess its biodistribution and internalization in Tn-expressing (Tn+) and wild-type (Tn-) LL/2 lung cancer cells. Results: Selective accumulation and gradual internalization of ChiTn were observed in Tn+ cells. Biodistribution in mice with both Tn+ or Tn- lung tumors indicated that the uptake of radiolabeled ChiTn within tumors increased over time. Dual-labeling experiments with 99mTc and 131I showed different biodistribution patterns, with 99mTc exhibiting higher values in the liver, spleen, and kidneys, while 131I showed higher uptake in the thyroid and stomach. However, tumor uptake did not significantly differ between Tn+ and Tn- tumors. To improve tumor targeting, Losartan, an antihypertensive drug known to enhance tumor perfusion and drug delivery, was investigated. Biodistribution studies in Losartan-treated mice revealed significantly higher radiolabeled ChiTn uptake in Tn+ tumors. No significant changes were observed in the uptake of the control molecule IgG-HYNIC™99mTc. Conclusions: These findings demonstrate the enhanced tumor targeting of radiolabeled ChiTn in Losartan-treated mice with Tn-expressing lung tumors. They highlight the potential of ChiTn as a theranostic agent for cancer treatment and emphasize the importance of Losartan as an adjunctive treatment to improve tumor perfusion and drug delivery.

Polydopamine-Coated Cu-BTC Nanowires for Effective Magnetic Resonance Imaging and Photothermal Therapy.

Herein, we present a one-pot hydrothermal approach for synthesizing metal-organic framework-derived copper (II) benzene-1,3,5-tricarboxylate (Cu-BTC) nanowires (NWs) using dopamine as the reducing agent and precursor for a polydopamine (PDA) surface coating formation. In addition, PDA can act as a PTT agent and enhance NIR absorption, producing photothermal effects on cancer cells. These NWs displayed a photothermal conversion efficiency of 13.32% after PDA coating and exhibited good photothermal stability. Moreover, NWs with a suitable T1 relaxivity coefficient (r1 = 3.01 mg-1 s-1) can be effectively used as magnetic resonance imaging (MRI) contrast agents. By increasing concentrations, cellular uptake studies showed a greater uptake of Cu-BTC@PDA NWs into cancer cells. Further, in vitro studies showed PDA-coated Cu-BTC NWs possess exceptional therapeutic performance by 808 nm laser irradiation, destroying 58% of cancer cells compared with the absence of laser irradiation. This promising performance is anticipated to advance the research and implementation of copper-based NWs as theranostic agents for cancer treatment.

Development of superior nanotheranostic agents with indocyanine green-conjugated poly(styrene-alt-maleic acid) nanoparticles for tumor imaging and phototherapy.

Developing safe, high-quality theranostic agents for cancer treatment is of great clinical value. In this work, for the first time, the clinical indocyanine green (ICG) is coupled with the biocompatible poly(styrene-alt-maleic anhydride) (PSMAn) to obtain the PSMAn-ICG polymer. The self-assembly of its hydrolyzed product in water results in ICG-conjugated poly(styrene-alt-maleic acid) nanoparticles (PSMA-ICG NPs). Intriguingly, the NPs have many advantages, including good solubility and stability in aqueous solutions, high photostability and decreased hemolytic damage to red blood cells, highlighting the importance of PSMA coupling. More interestingly, PSMA-ICG NPs significantly promote tumor targeting and enable long-term imaging of tumors. Furthermore, the administration of PSMA-ICG NPs in combination with near-infrared laser irradiation provides superior potency in the photothermal therapy of tumors. Furthermore, 9-amino-sialic acid (Sia)-coated PSMA-ICG NPs are fabricated, further enhancing tumor imaging and phototherapy. This is the first report of PSMA-NIR conjugates achieving tumor reduction in mice. Overall, this study provides novel phototheranostic agents with broad clinical transformation prospects.

Dual stimuli-responsive nanocarriers based on polyethylene glycol-mediated schiff base interactions for overcoming tumour chemoresistance

Multifunctional and stimulus-sensitive intelligent nanodrug delivery systems (NDDSs) can significantly optimize the effectiveness of theranostic agents for cancer treatment. In this study, redox and pH dual-responsive nanocarriers (CPNPs) were prepared through molecular assembly by utilizing the Schiff base interactions of cystamine (Cys), PEG-NH2 and formaldehyde (FA) under aqueous conditions with a one-pot, one-step technique. First, the degradation products of CPNPs exhibited good biocompatibility, and the high concentration of intact CPNPs (200 µg/mL) could inhibit the growth of cells. In addition, doxorubicin (DOX) was encapsulated in CPNPs simply by changing the pH (DOX@CPNPs), and pH/GSH-responsive release behaviour was confirmed. In vitro, CPNPs significantly increased the uptake of DOX and enhanced the cytotoxicity of DOX to tumour cells. More importantly, DOX@CPNPs strongly reversed drug resistance in three different types of cancer cells, exhibiting significant anticancer effects. Collectively, this study presents the easy preparation of nanomedicines that respond to multiple stimuli, which highlights the advantages of Schiff base-based nanomedicines for cancer therapy and reversing chemoresistance.

GdxFe3-xO4 nanoparticles with silane shell as potential theranostic agent for cancer treatment

In this study of GdxFe3-xO4 compound core silane shell nanoparticles method is represented.Samples were analyzed with SEM, EDA and FTIR spectroscopy. Further attaching of carborane compounds is discussed. Products can be used in biomedical applications for MRI imaging and drug delivery for NCT, so can be considered as potential theranostic agents for cancer treatment.

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One-pot bottom-up fabrication of biocompatible PEGylated WS2 nanoparticles for CT-guided photothermal therapy of tumors in vivo

BackgroundTungsten disulfide (WS2), which enjoyed a good potential to be a promising clinical theranostic agent for cancer treatment, is still subject to the tedious synthesis procedure. MethodsHere, we reported a one-pot ‘bottom-up’ hydrothermal strategy for the fabrication of PEGylated WS2 nanoparticles (NPs). The WS2-PEG nanoparticles were characterized systematically. The CT imaging and photothermal therapy against tumor as well as biosafety in vitro and in vivo were also investigated. ResultsThe obtained WS2-PEG NPs enjoyed obvious merits of good solubility and favorable photothermal performance. WS2-PEG NPs exhibited desirable photothermal ablation ability against cancer cells and cancer cell-bearing mice in vitro and in vivo. MTT assay and histological analysis demonstrated the low cytotoxicity and biotoxicity of WS2-PEG NPs, providing a valid biosafety guarantee for the coming biomedical applications. In addition, thanks to the obvious X-ray attenuation of W atom, the WS2-PEG NPs can also be served as a favorable contrast agent for CT imaging of tumors. ConclusionWS2-PEG NPs has enjoyed a good potential to be a promising clinical CT-guided photothermal therapeutic agent against cancers.

Polyetherimide-grafted Fe₃O₄@SiO2₂ nanoparticles as theranostic agents for simultaneous VEGF siRNA delivery and magnetic resonance cell imaging.

Engineering a safe and high-efficiency delivery system for efficient RNA interference is critical for successful gene therapy. In this study, we designed a novel nanocarrier system of polyethyleneimine (PEI)-modified Fe3O4@SiO2, which allows high efficient loading of VEGF small hairpin (sh)RNA to form Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites for VEGF gene silencing as well as magnetic resonance (MR) imaging. The size, morphology, particle stability, magnetic properties, and gene-binding capacity and protection were determined. Low cytotoxicity and hemolyticity against human red blood cells showed the excellent biocompatibility of the multifunctional nanocomposites, and also no significant coagulation was observed. The nanocomposites maintain their superparamagnetic property at room temperature and no appreciable change in magnetism, even after PEI modification. The qualitative and quantitative analysis of cellular internalization into MCF-7 human breast cancer cells by Prussian blue staining and inductively coupled plasma atomic emission spectroscopy analysis, respectively, demonstrated that the Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites could be easily internalized by MCF-7 cells, and they exhibited significant inhibition of VEGF gene expression. Furthermore, the MR cellular images showed that the superparamagnetic iron oxide core of our Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites could also act as a T2-weighted contrast agent for cancer MR imaging. Our data highlight multifunctional Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites as a potential platform for simultaneous gene delivery and MR cell imaging, which are promising as theranostic agents for cancer treatment and diagnosis in the future.

Platinum(II)–Gadolinium(III) Complexes as Potential Single‐Molecular Theranostic Agents for Cancer Treatment

AbstractTheranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)–gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt–Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd–DTPA. T1‐weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt–Gd complexes promising theranostic agents for cancer treatment.

Platinum(II)–Gadolinium(III) Complexes as Potential Single‐Molecular Theranostic Agents for Cancer Treatment

Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)-gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt-Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd-DTPA. T1-weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt-Gd complexes promising theranostic agents for cancer treatment.