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1.
J Mater Chem B ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34617547

RESUMO

Featuring simultaneous multicolor imaging for multiple targets, a synergistic strategy has become promising for fluorescence imaging applications. Visible and first near infrared (NIR-I, 700-900 nm) fluorophores have been explored for multicolor imaging to achieve good multi-target capacity, but they are largely hampered by the narrow imaging bands available (400-900 nm, bandwidth 500 nm), the broad emission spectra of many fluorophores, shallow tissue penetration and scattering loss. With attractive characteristic emission peaks in the second NIR window (NIR-II, 1000-1700 nm), a narrow emission spectrum, and deeper tissue penetration capability, rare-earth doped nanoparticles (RENPs) have been considered by us to be outstanding candidates for multicolor bioimaging. Herein, two RENPs, NaYF4:Yb20Er2@NaYF4 and NaYF4:Nd5@NaYF4, were prepared and modified with polyethylene glycol (PEG) to explore simultaneous imaging in the NIR-IIb (1530 nm, under 980 nm laser excitation) and the NIR-II (1060 nm, under 808 nm laser excitation) windows. The PEGylated-RENPs (RENPs@PEG) were able to simultaneously visualize the circulatory system, trace the lymphatic system, and evaluate the skeletal system. Our study demonstrates that RENPs have high synergistic imaging capability in multifunctional biomedical applications using their NIR-II fluorescence. Importantly, the two RENPs@PEG are complementary to each other for higher temporal resolution in NaYF4:Nd5@NaYF4@PEG and higher spatial resolution in NaYF4:Yb20Er2@NaYF4@PEG, which may provide more comprehensive and accurate imaging diagnosis. In conclusion, RENPs are highly promising nanomaterials for multicolor imaging in the NIR-II window.

2.
Clin Nucl Med ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34524169

RESUMO

ABSTRACT: A 61-year-old woman with low-set rectal adenocarcinoma (cT4bN1Mx) received radiotherapy and chemotherapy for 4 months, and then she underwent 18F-FDG PET/CT and 68Ga-FAPI PET/MR. Obviously increased 68Ga-FAPI uptake was unexpectedly revealed on both sides of the sacrum with low 18F-FDG uptake, which was diagnosed as insufficiency fracture based on the imaging features, advanced patient age, and radiotherapy history. The possibility of insufficiency fracture should be considered when accidental, symmetrically increased sacral 68Ga-FAPI uptake appears in cancer patients, and differential diagnosis should be carefully made.

3.
Theranostics ; 11(18): 9177-9179, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522233

RESUMO

Ideal nuclear imaging tracers should exhibit high target uptake and low background signal. Traditional renal scintigraphy and SPECT scans examine kidney function via static or dynamic tracing of radioactive probes in the kidneys. The lack of tracer affinity to specific biological processes and high background uptake from urinary excretion have added many difficulties to precision renal diagnosis. In this issue of Theranostics, Jin and colleagues innovatively devised a recombinant probe for preferential kidney imaging through targeting of tubular neonatal Fc receptor and proximal tubular basement membrane for sustained tubular reabsorption and accumulation. This work has broad implications regarding how an in depth understanding of physiology and pathology may be of service for tracer development, renal diagnosis, and disease theranostics.

4.
Mol Pharm ; 18(9): 3544-3552, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34482695

RESUMO

Maternal embryo leucine zipper kinase (MELK) is a serine/threonine kinase and is highly expressed in triple-negative breast cancer (TNBC). This study aimed to develop a 18F-radiolabeled tracer based on the structure of a small-molecule MELK inhibitor OTSSP167 and evaluate its application for PET imaging of MELK expression in TNBC. OTSSP167 was modified with ethylene glycol to adjust its pharmacokinetics and was then radiolabeled with 18F to obtain [18F]F-ET-OTSSP167 at a labeling yield of 7.14 ± 2.19% and a molar activity of 16.23 ± 1.13 MBq/nmol. In vitro binding assays showed differentiated binding affinities of [18F]F-ET-OTSSP167 in different breast cancer cell lines, with high uptake in MDA-MB-231 (mild MELK expression) and low uptake in MCF-7 (negative MELK expression). PET imaging revealed that MDA-MB-231 tumors could be clearly delineated in vivo, while low tracer uptake was observed in MCF-7 tumors. These findings were confirmed by ex vivo biodistribution studies and were consistent with the immunohistochemistry and tissue staining results. Tracer accumulation in MDA-MB-231 tumors was significantly inhibited by excess amounts of OTSSP167, indicating high specificity of the tracer. In summary, [18F]F-ET-OTSSP167, an easily-prepared probe, can be used to visualize MELK positive tumors, demonstrating its promising clinical potential in selecting patients for MELK inhibitor therapy.

5.
Front Immunol ; 12: 660842, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484174

RESUMO

Sphingosine-1-phosphate (S1P) is a phospholipid that regulates pleiotropic biological activities and exerts extracellular functions by binding to five specific G-protein-coupled receptors, S1P receptors (S1PR) 1-5. When activated by S1P, S1PR promote the proliferation and invasion of tumor cells by inducing the formation of new blood vessels. We developed and assessed a new monoclonal antibody imaging probe 99mTc-HYNIC-S1PR1mAb, to explore the feasibility of targeting the S1PR1 in vitro and in vivo. S1PR1mAb was prepared and followed by technetium-99m labeling with succinimidyl 6-hydraziniumnicotinate hydrochloride. Cell uptake and blocking studies were performed to investigate the binding specificity of 99mTc-HYNIC-S1PR1mAb in vitro. 99mTc-HYNIC-S1P1mAb was also tested in vivo in mice xenografted with SK-HEP-1 (high-expression of S1PR1) and MCF-7 (low-expression of S1PR1) using single-photon emission-computed tomography (SPECT). Ex vivo gamma counting of tissues from tumor-bearing mice was used to evaluate 99mTc-HYNIC-S1PR1mAb biodistribution. The biodistribution study results showed significantly higher uptake in SK-HEP-1 tumors than in MCF-7 tumors (P < 0.001). Reduced uptake of 99mTc-HYNIC-S1PR1mAb in SK-HEP-1 was observed in tumor-bearing nude mice pretreated with fingolimod, which binds competitively to the receptors, especially S1PR1. 99mTc-HYNIC-S1PR1mAb can be synthesized and specifically targeted to S1PR1 in vitro and in vivo, allowing S1PR1 expression assessment with SPECT imaging.


Assuntos
Anticorpos Monoclonais/química , Receptores de Esfingosina-1-Fosfato/análise , Tecnécio/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Animais , Anticorpos Monoclonais/administração & dosagem , Transporte Biológico , Linhagem Celular Tumoral , Feminino , Xenoenxertos , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Traçadores Radioativos , Receptores de Esfingosina-1-Fosfato/genética , Tecnécio/química , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Pharmaceutics ; 13(8)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34452187

RESUMO

Highly efficient drug delivery systems with excellent tumor selectivity and minimal toxicity to normal tissues remain challenging for tumor treatment. Although great effort has been made to prolong the blood circulation and improve the delivery efficiency to tumor sites, nanomedicines are rarely approved for clinical application. Bacteria have the inherent properties of homing to solid tumors, presenting themselves as promising drug delivery systems. Escherichia coli Nissle 1917 (EcN) is a commonly used probiotic in clinical practice. Its facultative anaerobic property drives it to selectively colonize in the hypoxic area of the tumor for survival and reproduction. EcN can be engineered as a bacteria-based microrobot for molecular imaging, drug delivery, and gene delivery. This review summarizes the progress in EcN-mediated tumor imaging and therapy and discusses the prospects and challenges for its clinical application. EcN provides a new idea as a delivery vehicle and will be a powerful weapon against cancer.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34241652

RESUMO

PURPOSE: To describe the uptake of 68Gallium-labelled fibroblast activation protein inhibitor (68Ga-FAPI) in the bones and joints for better understanding of the role of 68Ga-FAPI PET in benign and malignant bone lesions and joint diseases. METHODS: All 129 68Ga-FAPI PET/MR or PET/CT scans from June 1, 2020, to February 20, 2021, performed at our PET center were retrospectively reviewed. Foci of elevated 68Ga-FAPI uptake in the bones and joints were identified. All lesions were divided into malignant and benign diseases. Benign lesions included osteofibrous dysplasia, periodontitis, degenerative bone diseases, arthritis, and other inflammatory or trauma-related abnormalities. The number, locations, and SUVmax of all lesions were recorded and analyzed. The detectability of 68Ga-FAPI PET and 18F-FDG PET in patients who had two scans was also compared. RESULTS: Elevated uptake of 68Ga-FAPI in/around the bones and joints was found in 82 cases (63.57%). A total of 295 lesions were identified, including 94 (31.9%) malignant lesions (all were metastases) and 201 (68.1%) benign lesions. The benign lesions consisted of 13 osteofibrous dysplasia, 48 degenerative bone disease, 33 periodontitis, 56 arthritis, and 51 other inflammatory or trauma-related abnormalities. The spine, shoulder joint, alveolar ridge, and pelvis were the most commonly involved locations. Bone metastases were mainly distributed in the spine, pelvis, and ribs. Among benign diseases, periodontitis and arthritis are site-specific. The mean SUVmax of bone metastases was significantly higher than that of benign diseases (7.14 ± 4.33 vs. 3.57 ± 1.60, p < 0.001), but overlap existed. The differences in SUVmax among subgroups of benign diseases were statistically significant (p < 0.001), with much higher uptake in periodontitis (4.45 ± 1.17). 68Ga-FAPI PET identified much more lesions than 18F-FDG PET (104 vs. 48) with higher uptake value. CONCLUSION: 68Ga-FAPI accumulated in both bone metastases and some benign diseases of the bones and joints. Although the uptake of 68Ga-FAPI was often higher in bone metastases, this finding cannot be used to distinguish between benign and malignant lesions. 68Ga-FAPI PET also has the potential to locate and evaluate the extent of both malignant tumor and benign diseases in bones and joints. TRIAL REGISTRATION: NCT04554719, NCT04605939. Registered September 8, 2020 and October 25, 2020-retrospectively registered, http://clinicaltrails.gov/show/NCT04554719 ; http://clinicaltrails.gov/show/NCT04605939.

9.
Cancers (Basel) ; 13(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34298651

RESUMO

We explored the clinical value of 18F-FDG PET/MR in a head-to-head comparison with PET/CT in loco-regional recurrent and metastatic cervical lymph nodes of differentiated thyroid carcinoma (DTC) patients after comprehensive treatment. 18F-FDG PET/CT and neck PET/MR scans that were performed in DTC patients with suspected recurrence or cervical lymph node metastasis after comprehensive treatment were retrospectively analyzed. Detection rates, diagnostic efficacy, image conspicuity, and measured parameters were compared between 18F-FDG PET/CT and PET/MR. The gold standard was histopathological diagnosis or clinical and imaging follow-up results for more than 6 months. Among the 37 patients enrolled, no suspicious signs of tumor were found in 10 patients, 24 patients had lymph node metastasis, and 3 patients had both recurrence and lymph node metastases. A total of 130 lesions were analyzed, including 3 malignant and 6 benign thyroid nodules, as well as 74 malignant and 47 benign cervical lymph nodes. Compared with PET/CT, PET/MR presented better detection rates (91.5% vs. 80.8%), image conspicuity (2.74 ± 0.60 vs. 1.9 ± 0.50, p < 0.001, especially in complex level II), and sensitivity (80.5% vs. 61.0%). SUVmax differed in benign and malignant lymph nodes in both imaging modalities (p < 0.05). For the same lesion, the SUVmax, SUVmean, and diameters measured by PET/MR and PET/CT were consistent and had significant correlation. In conclusion, compared with 18F-FDG PET/CT, PET/MR was more accurate in determining recurrent and metastatic lesions, both from a patient-based and from a lesion-based perspective. Adding local PET/MR after whole-body PET/CT may be recommended to provide more precise diagnostic information and scope of surgical resection without additional ionizing radiation. Further scaling-up prospective studies and economic benefit analysis are expected.

10.
Theranostics ; 11(14): 6800-6817, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093854

RESUMO

Chimeric antigen receptor T cell (CAR-T) therapy is a new and effective form of adoptive cell therapy that is rapidly entering the mainstream for the treatment of CD19-positive hematological cancers because of its impressive effect and durable responses. Huge challenges remain in achieving similar success in patients with solid tumors. The current methods of monitoring CAR-T, including morphological imaging (CT and MRI), blood tests, and biopsy, have limitations to assess whether CAR-T cells are homing to tumor sites and infiltrating into tumor bed, or to assess the survival, proliferation, and persistence of CAR-T cells in solid tumors associated with an immunosuppressive microenvironment. Radionuclide-based molecular imaging affords improved CAR-T cellular visualization and therapeutic monitoring through either a direct cellular radiolabeling approach or a reporter gene imaging strategy, and endogenous cell imaging is beneficial to reflect functional information and immune status of T cells. Focusing on the dynamic monitoring and precise assessment of CAR-T therapy, this review summarizes the current applications of radionuclide-based noninvasive imaging in CAR-T cells visualization and monitoring and presents current challenges and strategic choices.


Assuntos
Antígenos de Neoplasias/imunologia , Imunoterapia Adotiva/métodos , Imagem Molecular/métodos , Neoplasias/diagnóstico por imagem , Receptores de Antígenos Quiméricos/uso terapêutico , Linfócitos T/imunologia , Microambiente Tumoral , Animais , Genes Reporter , Humanos , Camundongos , Radioisótopos , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Tomografia Computadorizada por Raios X , Ensaios Antitumorais Modelo de Xenoenxerto
13.
J Nanobiotechnology ; 19(1): 151, 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022897

RESUMO

BACKGROUD: Colon cancer contributes to high mortality rates as the result of incomplete resection in tumor surgery. Multimodal imaging can provide preoperative evaluation and intraoperative image-guiding. As biocompatible nanocarriers, extracellular vesicles hold great promise for multimodal imaging. In this study, we aim to synthesized an extracellular vesicles-based nanoprobe to visualize colon cancer with positron-emission tomography/computed tomography (PET/CT) and near-infrared fluorescence (NIRF) imaging, and investigated its utility in image-guided surgery of colon cancer in animal models. RESULTS: Extracellular vesicles were successfully isolated from adipose-derived stem cells (ADSCs), and their membrane vesicles were observed under TEM. DLS detected that the hydrodynamic diameters of the extracellular vesicles were approximately 140 nm and the zeta potential was - 7.93 ± 0.24 mV. Confocal microscopy showed that extracellular vesicles had a strong binding ability to tumor cells. A click chemistry-based pre-targeting strategy was used to achieve PET imaging in vivo. PET images and the biodistribution results showed that the best pre-targeting time was 20 h, and the best imaging time was 2 h after the injection of 68 Ga-L-NETA-DBCO. The NIRF images showed that the tumor had clear images at all time points after administration of nanoparticles and the Tumor/Muscle ratio peaked at 20 h after injection. Our data also showed that both PET/CT and NIRF imaging clearly visualized the orthotopic colon cancer models, providing preoperative evaluation. Under real-time NIRF imaging, the tumor location and tumor boundary could be clearly observed. CONCLUSIONS: In brief, this novel nanoprobe may be useful for multi-modal imaging of colon cancer and NIRF image-guided surgery. More importantly, this study provides a new possibility for clinical application of extracellular vesicles as nanocarriers.

14.
Eur J Nucl Med Mol Imaging ; 48(8): 2500-2524, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33932183

RESUMO

Medical imaging methods are assuming a greater role in the workup of patients with COVID-19, mainly in relation to the primary manifestation of pulmonary disease and the tissue distribution of the angiotensin-converting-enzyme 2 (ACE 2) receptor. However, the field is so new that no consensus view has emerged guiding clinical decisions to employ imaging procedures such as radiography, computer tomography (CT), positron emission tomography (PET), and magnetic resonance imaging, and in what measure the risk of exposure of staff to possible infection could be justified by the knowledge gained. The insensitivity of current RT-PCR methods for positive diagnosis is part of the rationale for resorting to imaging procedures. While CT is more sensitive than genetic testing in hospitalized patients, positive findings of ground glass opacities depend on the disease stage. There is sparse reporting on PET/CT with [18F]-FDG in COVID-19, but available results are congruent with the earlier literature on viral pneumonias. There is a high incidence of cerebral findings in COVID-19, and likewise evidence of gastrointestinal involvement. Artificial intelligence, notably machine learning is emerging as an effective method for diagnostic image analysis, with performance in the discriminative diagnosis of diagnosis of COVID-19 pneumonia comparable to that of human practitioners.


Assuntos
COVID-19 , Pneumonia Viral , Inteligência Artificial , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , SARS-CoV-2
15.
Eur J Nucl Med Mol Imaging ; 48(11): 3469-3481, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33829415

RESUMO

PURPOSE: To construct multivariate radiomics models using hybrid 18F-FDG PET/MRI for distinguishing between Parkinson's disease (PD) and multiple system atrophy (MSA). METHODS: Ninety patients (60 with PD and 30 with MSA) were randomized to training and test sets in a 7:3 ratio. All patients underwent 18F-fluorodeoxyglucose (18F-FDG) PET/MRI to simultaneously obtain metabolic images (18F-FDG), structural MRI images (T1-weighted imaging (T1WI), T2-weighted imaging (T2WI) and T2-weighted fluid-attenuated inversion recovery (T2/FLAIR)) and functional MRI images (susceptibility-weighted imaging (SWI) and apparent diffusion coefficient). Using PET and five MRI sequences, we extracted 1172 radiomics features from the putamina and caudate nuclei. The radiomics signatures were constructed with the least absolute shrinkage and selection operator algorithm in the training set, with progressive optimization through single-sequence and double-sequence radiomics models. Multivariable logistic regression analysis was used to develop a clinical-radiomics model, combining the optimal multi-sequence radiomics signature with clinical characteristics and SUV values. The diagnostic performance of the models was assessed by receiver operating characteristic and decision curve analysis (DCA). RESULTS: The radiomics signatures showed favourable diagnostic efficacy. The optimal model comprised structural (T1WI), functional (SWI) and metabolic (18F-FDG) sequences (RadscoreFDG_T1WI_SWI) with the area under curves (AUCs) of the training and test sets of 0.971 and 0.957, respectively. The integrated model, incorporating RadscoreFDG_T1WI_SWI, three clinical symptoms (disease duration, dysarthria and autonomic failure) and SUVmax, demonstrated satisfactory calibration and discrimination in the training and test sets (0.993 and 0.994, respectively). DCA indicated the highest clinical benefit of the clinical-radiomics integrated model. CONCLUSIONS: The radiomics signature with metabolic, structural and functional information provided by hybrid 18F-FDG PET/MRI may achieve promising diagnostic efficacy for distinguishing between PD and MSA. The clinical-radiomics integrated model performed best.

16.
Clin Nucl Med ; 46(9): 774-775, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33883497

RESUMO

ABSTRACT: 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET imaging has been introduced for detecting many primary and metastatic tumors. However, false-positive uptakes have been reported in some benign lesions. Here, we presented a 68Ga-FAPI-avid lesion in the left temporal bone in a 41-year-old man with a history of signet ring cell gastric adenocarcinoma. The osseous lesion was finally distinguished as fibrous dysplasia according to the clinical and imaging findings. This case suggests that 68Ga-FAPI may have false-positive uptakes in bone benign lesions, which should be paid attention to in the diagnosis of bone lesions in patients with malignant tumors.

17.
J Nucl Med ; 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863819

RESUMO

We sought to evaluate the performance of 68Ga-DOTA-FAPI-04 (68Ga-FAPI) PET/MR for the diagnosis of primary tumor and metastatic lesions in patients with gastric carcinomas and to compare the results with those of 18F-FDG PET/CT. Methods: Twenty patients with histologically proven gastric carcinomas were recruited, and each patient underwent both 18F-FDG PET/CT and 68Ga-FAPI PET/MR. A visual scoring system was established to compare the detectability of primary tumors and metastases in different organs/regions (the peritoneum, abdominal lymph nodes, supradiaphragmatic lymph nodes, liver, ovary, bone, and other tissues). The original maximum standardized uptake value (SUVmax) and normalized SUVmax (calculated by dividing a lesion's original SUVmax with the mean SUV of the descending aorta) of selected lesions on both 18F-FDG PET/CT and 68Ga-FAPI PET/MR were measured. Original/normalized SUVmax-FAPI and SUVmax-FDG were compared for patient-based (including a single lesion with the highest activity uptake in each organ/region) and lesion-based (including all lesions [≤ 5] or the 5 lesions with highest activity [> 5]) analyses, respectively. Results: The 20 recruited patients (median age: 56.0 y; range: 29-70 y) included 9 men and 11 women, 14 patients for initial staging and 6 for recurrence detection. 68Ga-FAPI PET was superior to 18F-FDG PET for primary tumor detection (100.00% [14/14] vs 71.43% [10/14], P = 0.034), and the former had higher tracer uptake levels (P < 0.05). 68Ga-FAPI PET was superior to 18F-FDG PET in both patient-based and lesion-based evaluation except for the metastatic lesions in supradiaphragmatic lymph nodes and ovaries. Additionally, multiple sequences of MR images were beneficial for the interpretation of hepatic metastases in 3 patients, uterine and rectal metastases in 1 patient, ovarian lesions in 7 patients, and osseous metastases in 2 patients. Conclusion: 68Ga-FAPI PET/MR outperformed 18F-FDG PET/CT in visualizing the primary and most metastatic lesions of gastric cancer, and might be a promising method with the potential of replacing 18F-FDG PET/CT.

18.
Front Immunol ; 12: 652924, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854512

RESUMO

As many patients ultimately relapse after chimeric antigen receptor (CAR) T-cell therapy, identification of alternative targets is currently being evaluated. Substantial research efforts are underway to develop new targets. The transferrin receptor (TfR) is prevalently expressed on rapidly proliferating tumor cells and holds the potential to be the alternative target. In order to investigate the efficacy and challenges of TfR-targeting on the CAR-based therapy strategy, we generated a TfR-specific CAR and established the TfR-CAR-modified T cells. To take the advantage of TfR being widely shared by multiple tumors, TfR-CAR T cells were assessed against several TfR+ hematological malignant cell lines. Data showed that TfR-CAR T cells were powerfully potent in killing all these types of cells in vitro and in killing T-ALL cells in vivo. These findings suggest that TfR could be a universal target to broaden and improve the therapeutic efficacy of CAR T cells and warrant further efforts to use these cells as an alternative CAR T cell product for the therapy of hematological malignancies.


Assuntos
Imunoterapia Adotiva/métodos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Receptores de Antígenos Quiméricos/metabolismo , Receptores da Transferrina/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/farmacologia , Camundongos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Receptores de Antígenos Quiméricos/genética , Receptores da Transferrina/antagonistas & inibidores , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
J Nanobiotechnology ; 19(1): 81, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33743740

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is a kind of aggressive breast cancer with a high rate of metastasis, poor overall survival time, and a low response to targeted therapies. To improve the therapeutic efficacy and overcome the drug resistance of TNBC treatments, here we developed the cancer cell membrane-coated oxygen delivery nanoprobe, CCm-HSA-ICG-PFTBA, which can improve the hypoxia at tumor sites and enhance the therapeutic efficacy of the photodynamic therapy (PDT), resulting in relieving the tumor growth in TNBC xenografts. RESULTS: The size of the CCm-HSA-ICG-PFTBA was 131.3 ± 1.08 nm. The in vitro 1O2 and ROS concentrations of the CCm-HSA-ICG-PFTBA group were both significantly higher than those of the other groups (P < 0.001). In vivo fluorescence imaging revealed that the best time window was at 24 h post-injection of the CCm-HSA-ICG-PFTBA. Both in vivo 18F-FMISO PET imaging and ex vivo immunofluorescence staining results exhibited that the tumor hypoxia was significantly improved at 24 h post-injection of the CCm-HSA-ICG-PFTBA. For in vivo PDT treatment, the tumor volume and weight of the CCm-HSA-ICG-PFTBA with NIR group were both the smallest among all the groups and significantly decreased compared to the untreated group (P < 0.01). No obvious biotoxicity was observed by the injection of CCm-HSA-ICG-PFTBA till 14 days. CONCLUSIONS: By using the high oxygen solubility of perfluorocarbon (PFC) and the homologous targeting ability of cancer cell membranes, CCm-HSA-ICG-PFTBA can target tumor tissues, mitigate the hypoxia of the tumor microenvironment, and enhance the PDT efficacy in TNBC xenografts. Furthermore, the HSA, ICG, and PFC are all FDA-approved materials, which render the nanoparticles highly biocompatible and enhance the potential for clinical translation in the treatment of TNBC patients.


Assuntos
Biomimética/métodos , Nanopartículas/uso terapêutico , Oxigênio , Fotoquimioterapia/métodos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/radioterapia , Animais , Mama/diagnóstico por imagem , Mama/patologia , Linhagem Celular Tumoral , Feminino , Fluorescência , Camundongos , Camundongos Endogâmicos BALB C , Técnicas de Sonda Molecular , Imagem Óptica/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
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