Nanotechnology strategies for hepatocellular carcinoma diagnosis and treatment

Jia, Weilu; Han, YingHui; Mao, Xinyu; Xu, Wenjing; Ye-wei, Zhang

doi:10.1039/d2ra05127c

Cited by 8 publications

(5 citation statements)

References 208 publications

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“…Alkaline degradation products of Mg could further neutralize the acidic microenvironment at the site of cancer lesions, thereby inhibiting cancer cells [ 20 ]. Meanwhile, metal nanomaterials themselves can be used to inhibit the growth of HepG2 cells, by incuring a variety of events such as mitochondrial damage, lysosome impairment, endoplasmic reticulum stress, and signalling pathway alterations [ 43 , 44 ]. Our result confirmed the enhancement of Mg in improving the 177 Lu radiation anti-tumor effect and prolonging survival time, suggesting 177 Lu-PDA-CS-MgO is a potential interventional radioembolization candidate for HCC therapy.…”

Section: Discussionmentioning

confidence: 99%

Polymer composite microspheres loading ¹⁷⁷ Lu radionuclide for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer

Xiao,

Li,

Geng

et al. 2023

Biomater Res

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Background Transarterial radioembolization (TARE) with 90Y-labeled glass and resin microspheres is one of the primary treatment strategies for advanced-stage primary and metastatic hepatocellular carcinoma (HCC). However, difficulties of real-time monitoring post administration and embolic hypoxia influence treatment prognosis. In this study, we developed a new biodegradable polymer microsphere that can simultaneously load 177Lu and MgO nanoparticle, and evaluated the TARE therapeutic efficacy and biosafety of 177Lu-PDA-CS-MgO microspheres for HCC treatment. Methods Chitosan microspheres were synthesized through emulsification crosslink reaction and then conducted surface modification with polydopamine (PDA). The 177Lu and nano MgO were conjugated to microspheres using active chemical groups of PDA. The characteristics of radionuclide loading efficiency, biodegradability, blood compatibility, and anti-tumor effectwere evaluated both in vitro and in vivo. SPECT/CT imaging was performed to monitor bio-distribution and bio-stability of 177Lu-PDA-CS-MgO after TARE treatment. The survival duration of each rat was monitored. HE analysis, TUNEL analysis, immunohistochemical analysis, and western blot analysis were conducted to explore the anti-tumor effect and mechanism of composited microspheres. Body weight, liver function, blood routine examination were monitored at different time points to evaluate the bio-safety of microspheres. Results The composite 177Lu-PDA-CS-MgO microsphere indicated satisfactory degradability, biocompatibility, radionuclide loading efficiency and radiochemical stability in vitro. Cellular evaluation showed that 177Lu-PDA-CS-MgO had significant anti-tumor effect and blocked tumor cell cycles in S phase. Surgical TARE treatment with 177Lu-PDA-CS-MgO significantly prolonged the medial survival time from 49 d to 105 d, and effectively inhibited primary tumor growth and small metastases spreading. Moreover, these microspheres indicated ideal in vivo stability and allowed real-time SPECT/CT monitoring for up to 8 weeks. Immunostaining and immunoblotting results also confirmed that 177Lu-PDA-CS-MgO had potential in suppressing tumor invasion and angiogenesis, and improved embolic hypoxia in HCC tissues. Further evaluations of body weight, blood test, and pathological analysis indicated good biosafety of 177Lu-PDA-CS-MgO microspheres in vivo. Conclusion Our study demonstrated that 177Lu-PDA-CS-MgO microsphere hold great potential as interventional brachytherapy candidate for HCC therapy. Graphical Abstract Polymer composite microspheres loading 177Lu radionuclide and MgO nanoparticles for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer.

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Section: Discussionmentioning

confidence: 99%

Polymer composite microspheres loading ¹⁷⁷ Lu radionuclide for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer

Xiao,

Li,

Geng

et al. 2023

Biomater Res

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“…Taking into account the anti-proliferative and anti-viral activity of IFNα-2b obtained magnetic conjugates SPIONs@IFNα-2b could be further employed for the treatment of various pathological conditions. Thus, as was shown by several studies, application of liver-targeted nanocomplexes could be employed for the efficient therapy of hepatitis C virus, human immunodeficiency virus, hepatocellular carcinoma (HCC) [ 60 , 61 , 62 , 63 , 64 ]. Furthermore, magnetic NPs labeled with IFNα-2b with high temporal–spatial resolution and directed towards the inflamed sites of liver parenchyma can be used for differential diagnostics of hepatic disorders [ 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

Magnetic Relaxation Switching Assay Using IFNα-2b-Conjugated Superparamagnetic Nanoparticles for Anti-Interferon Antibody Detection

et al. 2023

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Type I interferons, particularly IFNα-2b, play essential roles in eliciting adaptive and innate immune responses, being implicated in the pathogenesis of various diseases, including cancer, and autoimmune and infectious diseases. Therefore, the development of a highly sensitive platform for analysis of either IFNα-2b or anti-IFNα-2b antibodies is of high importance to improve the diagnosis of various pathologies associated with the IFNα-2b disbalance. For evaluation of the anti-IFNα-2b antibody level, we have synthesized superparamagnetic iron oxide nanoparticles (SPIONs) coupled with the recombinant human IFNα-2b protein (SPIONs@IFNα-2b). Employing a magnetic relaxation switching assay (MRSw)-based nanosensor, we detected picomolar concentrations (0.36 pg/mL) of anti-INFα-2b antibodies. The high sensitivity of the real-time antibodies’ detection was ensured by the specificity of immune responses and the maintenance of resonance conditions for water spins by choosing a high-frequency filling of short radio-frequency pulses of the generator. The formation of a complex of the SPIONs@IFNα-2b nanoparticles with the anti-INFα-2b antibodies led to a cascade process of the formation of nanoparticle clusters, which was further enhanced by exposure to a strong (7.1 T) homogenous magnetic field. Obtained magnetic conjugates exhibited high negative MR contrast-enhancing properties (as shown by NMR studies) that were also preserved when particles were administered in vivo. Thus, we observed a 1.2-fold decrease of the T2 relaxation time in the liver following administration of magnetic conjugates as compared to the control. In conclusion, the developed MRSw assay based on SPIONs@IFNα-2b nanoparticles represents an alternative immunological probe for the estimation of anti-IFNα-2b antibodies that could be further employed in clinical studies.

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“…The toxic side effects of chemotherapeutic drugs are often caused by non-specific ingestion and dose dependence. Therefore, the use of nanotechnology to improve the uptake of target cells and the duration of local blood concentrations of chemotherapy drugs is of great significance for enhancing the efficacy of chemotherapy and reducing the side effects of chemotherapy drugs ( Jia et al, 2022 ). The calcium carbonate nanoparticles were prepared by the microemulsion method.…”

Section: The Applications Of Nanotechnology-based Drugs In Hcc Treatmentmentioning

confidence: 99%

“…After the nanoparticles entered the endosome, its acidic environment helped the degradation of core components and promoted the release of cisplatin and NOR1 shRNA, which synergistically promoted the cisplatin resistance of HCC cells into cisplatin sensitivity ( Huang et al, 2023 ). Common chemotherapeutic drug nanoparticles have been listed in the reference ( Jia et al, 2022 ).…”

Section: The Applications Of Nanotechnology-based Drugs In Hcc Treatmentmentioning

confidence: 99%

The improving strategies and applications of nanotechnology-based drugs in hepatocellular carcinoma treatment

Ren,

Su,

Shi

et al. 2023

Front. Bioeng. Biotechnol.

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Hepatocellular carcinoma (HCC) is one of the leading causes of tumor-related death worldwide. Conventional treatments for HCC include drugs, radiation, and surgery. Despite the unremitting efforts of researchers, the curative effect of HCC has been greatly improved, but because HCC is often found in the middle and late stages, the curative effect is still not satisfactory, and the 5-year survival rate is still low. Nanomedicine is a potential subject, which has been applied to the treatment of HCC and has achieved promising results. Here, we summarized the factors affecting the efficacy of drugs in HCC treatment and the strategies for improving the efficacy of nanotechnology-based drugs in HCC, reviewed the recent applications’ progress on nanotechnology-based drugs in HCC treatment, and discussed the future perspectives and challenges of nanotechnology-based drugs in HCC treatment.

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Nanotechnology strategies for hepatocellular carcinoma diagnosis and treatment

Abstract: Hepatocellular carcinoma (HCC) is a common malignancy threatening human health, and existing diagnostic and therapeutic techniques are facing great challenges.

Cited by 8 publications

References 208 publications

Polymer composite microspheres loading ¹⁷⁷ Lu radionuclide for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer

Polymer composite microspheres loading ¹⁷⁷ Lu radionuclide for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer

Magnetic Relaxation Switching Assay Using IFNα-2b-Conjugated Superparamagnetic Nanoparticles for Anti-Interferon Antibody Detection

The improving strategies and applications of nanotechnology-based drugs in hepatocellular carcinoma treatment

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Nanotechnology strategies for hepatocellular carcinoma diagnosis and treatment

Abstract: Hepatocellular carcinoma (HCC) is a common malignancy threatening human health, and existing diagnostic and therapeutic techniques are facing great challenges.

Cited by 8 publications

References 208 publications

Polymer composite microspheres loading 177 Lu radionuclide for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer

Polymer composite microspheres loading 177 Lu radionuclide for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer

Magnetic Relaxation Switching Assay Using IFNα-2b-Conjugated Superparamagnetic Nanoparticles for Anti-Interferon Antibody Detection

The improving strategies and applications of nanotechnology-based drugs in hepatocellular carcinoma treatment

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Polymer composite microspheres loading ¹⁷⁷ Lu radionuclide for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer

Polymer composite microspheres loading ¹⁷⁷ Lu radionuclide for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer