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1.
J Nanobiotechnology ; 22(1): 235, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725031

RESUMO

Different from most of the conventional platforms with dissatisfactory theranostic capabilities, supramolecular nanotheranostic systems have unparalleled advantages via the artful combination of supramolecular chemistry and nanotechnology. Benefiting from the tunable stimuli-responsiveness and compatible hierarchical organization, host-guest interactions have developed into the most popular mainstay for constructing supramolecular nanoplatforms. Characterized by the strong and diverse complexation property, cucurbit[8]uril (CB[8]) shows great potential as important building blocks for supramolecular theranostic systems. In this review, we summarize the recent progress of CB[8]-based supramolecular theranostics regarding the design, manufacture and theranostic mechanism. Meanwhile, the current limitations and corresponding reasonable solutions as well as the potential future development are also discussed.


Assuntos
Hidrocarbonetos Aromáticos com Pontes , Imidazóis , Nanomedicina Teranóstica , Nanomedicina Teranóstica/métodos , Hidrocarbonetos Aromáticos com Pontes/química , Imidazóis/química , Humanos , Animais , Nanopartículas/química , Compostos Heterocíclicos com 2 Anéis , Compostos Macrocíclicos , Imidazolidinas
2.
Sci Rep ; 14(1): 10646, 2024 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724530

RESUMO

Individual theranostic agents with dual-mode MRI responses and therapeutic efficacy have attracted extensive interest due to the real-time monitor and high effective treatment, which endow the providential treatment and avoid the repeated medication with side effects. However, it is difficult to achieve the integrated strategy of MRI and therapeutic drug due to complicated synthesis route, low efficiency and potential biosafety issues. In this study, novel self-assembled ultrasmall Fe3O4 nanoclusters were developed for tumor-targeted dual-mode T1/T2-weighted magnetic resonance imaging (MRI) guided synergetic chemodynamic therapy (CDT) and chemotherapy. The self-assembled ultrasmall Fe3O4 nanoclusters synthesized by facilely modifying ultrasmall Fe3O4 nanoparticles with 2,3-dimercaptosuccinic acid (DMSA) molecule possess long-term stability and mass production ability. The proposed ultrasmall Fe3O4 nanoclusters shows excellent dual-mode T1 and T2 MRI capacities as well as favorable CDT ability due to the appropriate size effect and the abundant Fe ion on the surface of ultrasmall Fe3O4 nanoclusters. After conjugation with the tumor targeting ligand Arg-Gly-Asp (RGD) and chemotherapy drug doxorubicin (Dox), the functionalized Fe3O4 nanoclusters achieve enhanced tumor accumulation and retention effects and synergetic CDT and chemotherapy function, which serve as a powerful integrated theranostic platform for cancer treatment.


Assuntos
Imageamento por Ressonância Magnética , Nanomedicina Teranóstica , Imageamento por Ressonância Magnética/métodos , Nanomedicina Teranóstica/métodos , Animais , Camundongos , Humanos , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Linhagem Celular Tumoral , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Succímero/química , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia
3.
J Inorg Biochem ; 256: 112569, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38701687

RESUMO

The clinical success of [223Ra]RaCl2 (Xofigo®) for the palliative treatment of bone metastases in patients with prostate cancer has highlighted the therapeutic potential of α-particle emission. Expanding the applicability of radium-223 in Targeted Alpha Therapy of non-osseous tumors is followed up with significant interest, as it holds the potential to unveil novel treatment options in the comprehensive management of cancer. Moreover, the use of barium radionuclides, like barium-131 and -135m, is still unfamiliar in nuclear medicine applications, although they can be considered as radium-223 surrogates for imaging purposes. Enabling these applications requires the establishment of chelators able to form stable complexes with radium and barium radionuclides. Until now, only a limited number of ligands have been suggested and these molecules have been primarily inspired by existing structures known for their ability to complex large metal cations. However, a systematic inspection of chelators specifically tailored to Ra2+ and Ba2+ has yet to be conducted. This work delves into a comprehensive investigation of a series of small organic ligands, aiming to unveil the coordination preferences of both radium-223 and barium-131/135m. Electronic binding energies of both metal cations to each ligand were theoretically computed via Density Functional Theory calculations (COSMO-ZORA-PBE-D3/TZ2P), while thermodynamic stability constants were experimentally determined for Ba2+-ligand complexes by potentiometry, NMR and UV-Vis spectroscopies. The outcomes revealed malonate, 2-hydroxypyridine 1-oxide and picolinate as the most favorable building blocks to design multidentate chelators. These findings serve as foundation guidelines, propelling the development of cutting-edge radium-223- and barium-131/135m-based radiopharmaceuticals for Targeted Alpha Therapy and theranostics of cancer.


Assuntos
Rádio (Elemento) , Rádio (Elemento)/química , Rádio (Elemento)/uso terapêutico , Humanos , Radioisótopos/química , Complexos de Coordenação/química , Complexos de Coordenação/uso terapêutico , Bário/química , Partículas alfa/uso terapêutico , Quelantes/química , Quelantes/uso terapêutico , Neoplasias/tratamento farmacológico , Nanomedicina Teranóstica/métodos , Metais Alcalinoterrosos/química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/uso terapêutico
5.
Int J Mol Sci ; 25(9)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38732200

RESUMO

We are living in an era of advanced nanoscience and nanotechnology. Numerous nanomaterials, culminating in nanorobots, have demonstrated ingenious applications in biomedicine, including breast cancer (BC) nano-theranostics. To solve the complicated problem of BC heterogeneity, non-targeted drug distribution, invasive diagnostics or surgery, resistance to classic onco-therapies and real-time monitoring of tumors, nanorobots are designed to perform multiple tasks at a small scale, even at the organelles or molecular level. Over the last few years, most nanorobots have been bioengineered as biomimetic and biocompatible nano(bio)structures, resembling different organisms and cells, such as urchin, spider, octopus, fish, spermatozoon, flagellar bacterium or helicoidal cyanobacterium. In this review, readers will be able to deepen their knowledge of the structure, behavior and role of several types of nanorobots, among other nanomaterials, in BC theranostics. We summarized here the characteristics of many functionalized nanodevices designed to counteract the main neoplastic hallmark features of BC, from sustaining proliferation and evading anti-growth signaling and resisting programmed cell death to inducing angiogenesis, activating invasion and metastasis, preventing genomic instability, avoiding immune destruction and deregulating autophagy. Most of these nanorobots function as targeted and self-propelled smart nano-carriers or nano-drug delivery systems (nano-DDSs), enhancing the efficiency and safety of chemo-, radio- or photodynamic therapy, or the current imagistic techniques used in BC diagnosis. Most of these nanorobots have been tested in vitro, using various BC cell lines, as well as in vivo, mainly based on mice models. We are still waiting for nanorobots that are low-cost, as well as for a wider transition of these favorable effects from laboratory to clinical practice.


Assuntos
Neoplasias da Mama , Nanotecnologia , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Neoplasias da Mama/diagnóstico , Feminino , Nanotecnologia/métodos , Animais , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Robótica/métodos , Nanomedicina Teranóstica/métodos , Sistemas de Liberação de Medicamentos/métodos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia
6.
Theranostics ; 14(6): 2490-2525, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646646

RESUMO

Inflammatory dysregulation is intimately associated with the occurrence and progression of many life-threatening diseases. Accurate detection and timely therapeutic intervention on inflammatory dysregulation are crucial for the effective therapy of inflammation-associated diseases. However, the clinical outcomes of inflammation-involved disorders are still unsatisfactory. Therefore, there is an urgent need to develop innovative anti-inflammatory strategies by integrating emerging technological innovations with traditional therapeutics. Biomedical nanotechnology is one of the promising fields that can potentially transform the diagnosis and treatment of inflammation. In this review, we outline recent advances in biomedical nanotechnology for the diagnosis and treatment of inflammation, with special attention paid to nanosensors and nanoprobes for precise diagnosis of inflammation-related diseases, emerging anti-inflammatory nanotherapeutics, as well as nanotheranostics and combined anti-inflammatory applications. Moreover, the prospects and challenges for clinical translation of nanoprobes and anti-inflammatory nanomedicines are highlighted.


Assuntos
Inflamação , Nanotecnologia , Nanomedicina Teranóstica , Humanos , Inflamação/diagnóstico , Nanomedicina Teranóstica/métodos , Nanotecnologia/métodos , Animais , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Nanomedicina/métodos , Nanopartículas
7.
ACS Biomater Sci Eng ; 10(5): 2703-2724, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38644798

RESUMO

The scientific world is increasingly focusing on rare earth metal oxide nanomaterials due to their consequential biological prospects, navigated by breakthroughs in biomedical applications. Terbium belongs to rare earth elements (lanthanide series) and possesses remarkably strong luminescence at lower energy emission and signal transduction properties, ushering in wide applications for diagnostic measurements (i.e., bioimaging, biosensors, fluorescence imaging, etc.) in the biomedical sectors. In addition, the theranostic applications of terbium-based nanoparticles further permit the targeted delivery of drugs to the specific site of the disease. Furthermore, the antimicrobial properties of terbium nanoparticles induced via reactive oxygen species (ROS) cause oxidative damage to the cell membrane and nuclei of living organisms, ion release, and surface charge interaction, thus further creating or exhibiting excellent antioxidant characteristics. Moreover, the recent applications of terbium nanoparticles in tissue engineering, wound healing, anticancer activity, etc., due to angiogenesis, cell proliferation, promotion of growth factors, biocompatibility, cytotoxicity mitigation, and anti-inflammatory potentials, make this nanoparticle anticipate a future epoch of nanomaterials. Terbium nanoparticles stand as a game changer in the realm of biomedical research, proffering a wide array of possibilities, from revolutionary imaging techniques to advanced drug delivery systems. Their unique properties, including luminescence, magnetic characteristics, and biocompatibility, have redefined the boundaries of what can be achieved in biomedicine. This review primarily delves into various mechanisms involved in biomedical applications via terbium-based nanoparticles due to their physicochemical characteristics. This review article further explains the potential biomedical applications of terbium nanoparticles with in-depth significant mechanisms from the individual literature. This review additionally stands as the first instance to furnish a "single-platted" comprehensive acquaintance of terbium nanoparticles in shaping the future of healthcare as well as potential limitations and overcoming strategies that require exploration before being trialed in clinical settings.


Assuntos
Térbio , Humanos , Térbio/química , Animais , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Engenharia Tecidual/métodos , Nanomedicina Teranóstica/métodos , Sistemas de Liberação de Medicamentos/métodos
8.
Theranostics ; 14(6): 2367-2378, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646652

RESUMO

The field of theranostics is rapidly advancing, driven by the goals of enhancing patient care. Recent breakthroughs in artificial intelligence (AI) and its innovative theranostic applications have marked a critical step forward in nuclear medicine, leading to a significant paradigm shift in precision oncology. For instance, AI-assisted tumor characterization, including automated image interpretation, tumor segmentation, feature identification, and prediction of high-risk lesions, improves diagnostic processes, offering a precise and detailed evaluation. With a comprehensive assessment tailored to an individual's unique clinical profile, AI algorithms promise to enhance patient risk classification, thereby benefiting the alignment of patient needs with the most appropriate treatment plans. By uncovering potential factors unseeable to the human eye, such as intrinsic variations in tumor radiosensitivity or molecular profile, AI software has the potential to revolutionize the prediction of response heterogeneity. For accurate and efficient dosimetry calculations, AI technology offers significant advantages by providing customized phantoms and streamlining complex mathematical algorithms, making personalized dosimetry feasible and accessible in busy clinical settings. AI tools have the potential to be leveraged to predict and mitigate treatment-related adverse events, allowing early interventions. Additionally, generative AI can be utilized to find new targets for developing novel radiopharmaceuticals and facilitate drug discovery. However, while there is immense potential and notable interest in the role of AI in theranostics, these technologies do not lack limitations and challenges. There remains still much to be explored and understood. In this study, we investigate the current applications of AI in theranostics and seek to broaden the horizons for future research and innovation.


Assuntos
Inteligência Artificial , Neoplasias , Medicina de Precisão , Humanos , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Neoplasias/diagnóstico , Neoplasias/terapia , Algoritmos , Nanomedicina Teranóstica/métodos , Nanomedicina Teranóstica/tendências
9.
Theranostics ; 14(6): 2464-2488, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646648

RESUMO

Cancer has remained a formidable challenge in medicine and has claimed an enormous number of lives worldwide. Theranostics, combining diagnostic methods with personalized therapeutic approaches, shows huge potential to advance the battle against cancer. This review aims to provide an overview of theranostics in oncology: exploring its history, current advances, challenges, and prospects. We present the fundamental evolution of theranostics from radiotherapeutics, cellular therapeutics, and nanotherapeutics, showcasing critical milestones in the last decade. From the early concept of targeted drug delivery to the emergence of personalized medicine, theranostics has benefited from advances in imaging technologies, molecular biology, and nanomedicine. Furthermore, we emphasize pertinent illustrations showcasing that revolutionary strategies in cancer management enhance diagnostic accuracy and provide targeted therapies customized for individual patients, thereby facilitating the implementation of personalized medicine. Finally, we describe future perspectives on current challenges, emerging topics, and advances in the field.


Assuntos
Neoplasias , Medicina de Precisão , Nanomedicina Teranóstica , Humanos , Neoplasias/terapia , Neoplasias/diagnóstico , Nanomedicina Teranóstica/métodos , Medicina de Precisão/métodos , Sistemas de Liberação de Medicamentos/métodos , Nanomedicina/métodos , História do Século XX , Animais , História do Século XXI
10.
J Med Chem ; 67(9): 7431-7442, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38664896

RESUMO

Since hydrogen sulfide (H2S) is an important endogenous gaseous mediator, therapeutic manipulation of H2S is promising for anticancer treatment. In this work, we develop a novel theranostic nanoplatform with H2S-specific and photocontrolled synergistic activation for imaging-guided H2S depletion and downregulation along with promoted photothermal therapy. Such a nanoplatform is fabricated by integration of a H2S-responsive molecule probe that can generate a cystathionine-ß-synthase (CBS) inhibitor AOAA and a photothermal transducer into an NIR-light-responsive container. Our nanoplatform can turn on NIR fluorescence specifically in H2S-rich cancers, guiding further laser irradiation. Furthermore, prominent conversion of photoenergy into heat guarantees special container melting with controllable AOAA release for H2S-level downregulation. This smart regulation of the endogenous H2S level amplifies the PTT therapeutic effect, successfully suppressing colorectal tumor in living mice under NIR fluorescence imaging guidance. Thus, we believe that this nanoplatform may provide a powerful tool toward H2S-concerned cancer treatment with an optimized diagnostic and therapeutic effect.


Assuntos
Neoplasias Colorretais , Regulação para Baixo , Sulfeto de Hidrogênio , Terapia Fototérmica , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/química , Animais , Terapia Fototérmica/métodos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , Humanos , Camundongos , Regulação para Baixo/efeitos dos fármacos , Cistationina beta-Sintase/metabolismo , Cistationina beta-Sintase/antagonistas & inibidores , Imagem Óptica , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Raios Infravermelhos , Linhagem Celular Tumoral , Nanomedicina Teranóstica/métodos
11.
Tomography ; 10(4): 554-573, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38668401

RESUMO

This review provides unique insights to the scientific scope and clinical visions of the inventors and pioneers of the SoftVue breast tomographic ultrasound (BTUS). Their >20-year collaboration produced extensive basic research and technology developments, culminating in SoftVue, which recently received the Food and Drug Administration's approval as an adjunct to breast cancer screening in women with dense breasts. SoftVue's multi-center trial confirmed the diagnostic goals of the tissue characterization and localization of quantitative acoustic tissue differences in 2D and 3D coronal image sequences. SoftVue mass characterizations are also reviewed within the standard cancer risk categories of the Breast Imaging Reporting and Data System. As a quantitative diagnostic modality, SoftVue can also function as a cost-effective platform for artificial intelligence-assisted breast cancer identification. Finally, SoftVue's quantitative acoustic maps facilitate noninvasive temperature monitoring and a unique form of time-reversed, focused US in a single theranostic device that actually focuses acoustic energy better within the highly scattering breast tissues, allowing for localized hyperthermia, drug delivery, and/or ablation. Women also prefer the comfort of SoftVue over mammograms and will continue to seek out less-invasive breast care, from diagnosis to treatment.


Assuntos
Neoplasias da Mama , Ultrassonografia Mamária , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Feminino , Ultrassonografia Mamária/métodos , Detecção Precoce de Câncer/métodos , Nanomedicina Teranóstica/métodos , Mama/diagnóstico por imagem , Mama/patologia
12.
Curr Oncol Rep ; 26(5): 538-550, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38581469

RESUMO

PURPOSE OF REVIEW: This paper aims to address the latest findings in neuroendocrine tumor (NET) theranostics, focusing on new evidence and future directions of combined diagnosis with positron emission tomography (PET) and treatment with peptide receptor radionuclide therapy (PRRT). RECENT FINDINGS: Following NETTER-1 trial, PRRT with [177Lu]Lu-DOTATATE was approved by FDA and EMA and is routinely employed in advanced G1 and G2 SST (somatostatin receptor)-expressing NET. Different approaches have been proposed so far to improve the PRRT therapeutic index, encompassing re-treatment protocols, combinations with other therapies and novel indications. Molecular imaging holds a potential added value in characterizing disease biology and heterogeneity using different radiopharmaceuticals (e.g., SST and FDG) and may provide predictive and prognostic parameters. Response assessment criteria are still an unmet need and new theranostic pairs showed preliminary encouraging results. PRRT for NET has become a paradigm of modern theranostics. PRRT holds a favorable toxicity profile, and it is associated with a prolonged time to progression, reduction of symptoms, and improved patients' quality of life. In light of further optimization, different new strategies have been investigated, along with the development of new radiopharmaceuticals.


Assuntos
Tumores Neuroendócrinos , Octreotida/análogos & derivados , Compostos Organometálicos , Compostos Radiofarmacêuticos , Humanos , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/diagnóstico por imagem , Compostos Radiofarmacêuticos/uso terapêutico , Octreotida/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Receptores de Peptídeos/uso terapêutico , Receptores de Peptídeos/metabolismo , Nanomedicina Teranóstica/métodos , Radioisótopos/uso terapêutico
13.
Mol Pharm ; 21(5): 2544-2554, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38588328

RESUMO

Vascular endothelial growth factor (VEGF) targeted therapy serves as an important therapeutic approach for renal cancer, but its clinical effectiveness is unsatisfactory. Moreover, there is a lack of reliable biomarkers for preoperative assessment of tumor VEGF expression. This study aimed to explore the potential for further applications of 177Lu/89Zr-labeled aflibercept (Abe), a VEGF-binding agent, in imaging visualization of VEGF expression and therapy for renal cancer. To determine specificity uptake in renal cancer, BALB/c mice with VEGF-expressing Renca tumor were intravenously injected with [89Zr]Zr-Abe, [177Lu]Lu-Abe, or Cy5.5-Abe and the blocking group was designed as a control group. PET, SPECT, and fluorescence images were acquired, and the biodistribution of [89Zr]Zr-Abe and [177Lu]Lu-Abe was performed. Additionally, the [177Lu]Lu-Abe, [177Lu]Lu-Abe-block, 177Lu only, Abe only, and PBS groups were compared for evaluation of the therapeutic effect. To assess the safety, we monitored and evaluated the body weight, blood biochemistry analysis, and whole blood analysis and major organs were stained with hematoxylin and eosin after [177Lu]Lu-Abe treatment. DOTA-Abe was successfully labeled with 177Lu and Df-Abe with 89Zr in our study. The uptake in tumor of [89Zr]Zr-Abe was significantly higher than that of [89Zr]Zr-Abe-block (P < 0.05) and provided excellent tumor contrast in PET images. [177Lu]Lu-Abe demonstrated promising tumor-specific targeting capability with a high and persistent tumor uptake. The standardized tumor volume of [177Lu]Lu-Abe was significantly smaller than those of other treatment groups (P < 0.05). [177Lu]Lu-Abe also had smaller tumor volumes and reduced expression of VEGF and CD31 compared to those of the control groups. Fluorescence images demonstrate higher tumor uptake in the Cy5.5-Abe group compared to the Cy5.5-Abe-block group (P < 0.05). In conclusion, [89Zr]Zr-Abe enables noninvasive analysis of VEGF expression, serving as a valuable tool for assessing the VEGF-targeted therapy effect. Additionally, all of the findings support the enhanced therapeutic efficacy and safety of [177Lu]Lu-Abe, making it a viable option for clinical practice in renal cancer.


Assuntos
Neoplasias Renais , Lutécio , Camundongos Endogâmicos BALB C , Radioisótopos , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Zircônio , Animais , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/farmacocinética , Zircônio/química , Camundongos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/metabolismo , Distribuição Tecidual , Humanos , Linhagem Celular Tumoral , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/química , Nanomedicina Teranóstica/métodos , Feminino , Tomografia por Emissão de Pósitrons/métodos , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Mol Pharm ; 21(5): 2415-2424, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38606663

RESUMO

Chemokines and chemokine receptors are indispensable to play a key role in the development of malignant tumors. As one of the most widely expressed chemokine receptors, chemokine (C-X-C motif) receptor 4 (CXCR4) has been a popular research focus. In most tumors, CXCR4 expression is significantly upregulated. Moreover, integrated nuclide diagnosis and therapy targeting CXCR4 show great potential. [68Ga]Ga-pentixafor, a radioligand targeting CXCR4, exhibits a strong affinity for CXCR4 both in vivo and in vitro. However, [177Lu]Lu-pentixather, the therapeutic companion of [68Ga]Ga-pentixafor, requires significant refinement to mitigate its pronounced hepatic biodistribution. The objective of this study was to synthesize theranostic molecular tracers with superior CXCR4 targeting functions. The Daudi cell line, which highly expressed CXCR4, and the MM.1S cell line, which weakly expressed CXCR4, were used in this study. Based on the pharmacophore cyclo (-d-Tyr-n-me-d-Orn-l-Arg-L-2-NAL-Gly-) (CPCR4) of pentixafor, six tracers were synthesized: [124I]I-1 ([124I]I-CPCR4), [99mTc]Tc-2 ([99mTc]Tc-HYNIC-CPCR4), [124I]I-3 ([124I]I-pentixafor), [18F]AlF-4 ([18F]AlF-NETA-CPCR4), [99mTc]Tc-5 ([99mTc]Tc-MAG3-CPCR4) and [124I]I-6 ([124I]I-pentixafor-Ga) and their radiochemical purities were all higher than 95%. After positron emission tomography (PET)/single-photon emission computed tomography (SPECT) imaging, the [124I]I-6 group exhibited the best target-nontarget ratio. At the same time, comparing the [68Ga]Ga-pentixafor group with the [124I]I-6 group, we found that the [124I]I-6 group had a better target-nontarget ratio and lower uptake in nontarget organs. Therefore, compound 6 was selected for therapeutic radionuclide (131I) labeling, and the tumor-bearing animal models were treated with [131I]I-6. The volume of the tumor site was significantly reduced in the treatment group compared with the control group, and no significant side effects were found. [124I]I-6 and [131I]I-6 showed excellent affinity for targeting CXCR4, and they showed great potential for the integrated diagnosis and treatment of tumors with high CXCR4 expression.


Assuntos
Complexos de Coordenação , Receptores CXCR4 , Receptores CXCR4/metabolismo , Receptores CXCR4/genética , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Distribuição Tecidual , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/farmacologia , Compostos Radiofarmacêuticos/química , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Sondas Moleculares/química , Sondas Moleculares/farmacocinética , Radioisótopos de Gálio , Camundongos Nus , Nanomedicina Teranóstica/métodos , Feminino
15.
Med Oncol ; 41(6): 132, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687401

RESUMO

Lung cancer is the leading cause of death in cancer across the globe. To minimize these deaths, the replacement of traditional chemotherapy with novel strategies is significant. We have developed a nanotheranostic approach using silver nanoparticles for imaging and treatment. Silver nanoparticles (AgNPs) are fabricated by chemical reduction method. The formulation of AgNPs was confirmed by different characterization techniques like stability test, UV-Visible spectroscopy, Confocal Raman Spectroscopy, and Energy-Dispersive X-ray analysis. Further, AgNPs are coated with poly lactic-co-glycolic acid (PLGA) and then loaded with paclitaxel (Pac). Then the drug-loaded PLGA-coated AgNPs were characterized for size and zeta potential measurement by zetasizer, surface morphology study by atomic force microscopy, Fourier transform infrared spectroscopy, and release kinetics study. The imaging and anticancer properties of these nanoformulations are investigated using lung cancer cell lines. The results proved that the particles are in the nanometer range with smooth surface morphology. Moreover, the drug-loaded NPs showed a sustained release of the drug for a longer period of time. Further the formulations showed imaging property with greater anticancer efficacy. Thus, the results suggest the effective use of these nanoformulation in both lung cancer imaging and treatment using a simple and efficient approach.


Assuntos
Neoplasias Pulmonares , Nanopartículas Metálicas , Paclitaxel , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Prata , Nanomedicina Teranóstica , Prata/química , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Nanopartículas Metálicas/química , Paclitaxel/administração & dosagem , Paclitaxel/química , Nanomedicina Teranóstica/métodos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Linhagem Celular Tumoral , Células A549
16.
Biomater Adv ; 160: 213833, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38564997

RESUMO

Conventional chemotherapy and poor targeted delivery in brain cancer resulting to poor treatment and develop resistance to anticancer drugs. Meanwhile, it is quite challenging to diagnose/detection of brain tumor at early stage of cancer which resulting in severity of the disease. Despite extensive research, effective treatment with real-time imaging still remains completely unavailable, yet. In this study, two brain cancer cell specific moieties i.e., AS1411 aptamer and RGD are decorated on the surface of chitosan-PLGA nanoparticles to improve targeted co-delivery of docetaxel (DTX) and upconversion nanoparticles (UCNP) for effective brain tumor therapy and real-time imaging. The nanoparticles were developed by a slightly modified emulsion/solvent evaporation method. This investigation also translates the successful synthesis of TPGS-chitosan, TPGS-RGD and TPGS-AS1411 aptamer conjugates for making PLGA nanoparticle as a potential tool of the targeted co-delivery of DTX and UCNP to the brain cancer cells. The developed nanoparticles have shown an average particle size <200 nm, spherical in shape, high encapsulation of DTX and UCNP in the core of nanoparticles, and sustained release of DTX up to 72 h in phosphate buffer saline (pH 7.4). AS1411 aptamer and RGD functionalized theranostic chitosan-PLGA nanoparticles containing DTX and UCNP (DUCPN-RGD-AS1411) have achieved greater cellular uptake, 89-fold improved cytotoxicity, enhanced cancer cell arrest even at lower drug conc., improved bioavailability with higher mean residence time of DTX in systemic circulation and brain tissues. Moreover, DUCPN-RGD-AS1411 have greatly facilitated cellular internalization and higher accumulation of UCNP in brain tissues. Additionally, DUCPN-RGD-AS1411 demonstrated a significant suppression in tumor growth in brain-tumor bearing xenograft BALB/c nude mice with no impressive sign of toxicities. DUCPN-RGD-AS1411 has great potential to be utilized as an effective and safe theranostic tool for brain cancer and other life-threatening cancer therapies.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias Encefálicas , Quitosana , Docetaxel , Nanopartículas , Oligodesoxirribonucleotídeos , Oligopeptídeos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Nanomedicina Teranóstica , Quitosana/química , Nanopartículas/química , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Aptâmeros de Nucleotídeos/administração & dosagem , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/farmacocinética , Humanos , Animais , Docetaxel/farmacocinética , Docetaxel/administração & dosagem , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Oligopeptídeos/química , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Nanomedicina Teranóstica/métodos , Linhagem Celular Tumoral , Camundongos , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Antineoplásicos/química
17.
Biomaterials ; 308: 122561, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38603827

RESUMO

Fungi infection is a serious threat to public health, but an effective antifungal strategy remains a challenge. Herein, a biomimetic nanocomposite with multifunctionalities, including fungi diagnosis, antifungal adhesion, precise fungi elimination, and cytokine sequestration, is constructed for battling Candida albicans (C. albicans) infection. By screening a range of cells, we find that the polarized macrophage cells have the strongest binding tendency toward C. albicans. Thus, their membranes were exfoliated to camouflage UCNPs and then decorated with photosensitizers (methylene blue, MB) and DNA sensing elements. The resulting nanocomposite can tightly bind to fungal surfaces, promote DNA recognition, and squeeze pro-inflammatory cytokines to relieve inflammation. Consequently, this nanocomposite can detect C. albicans with enhanced sensitivity and precisely eliminate fungal cells through photodynamic therapy with minimal phototoxicity because of its switchable fluorescence behavior. The developed nanocomposite with good biocompatibility achieves a satisfactory diagnostic and therapeutic effect in a C. albicans-infected mouse model, which offers a unique approach to fight fungi infection.


Assuntos
Antifúngicos , Materiais Biomiméticos , Candida albicans , Candidíase , Nanocompostos , Nanomedicina Teranóstica , Animais , Nanocompostos/química , Camundongos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Candidíase/tratamento farmacológico , Candidíase/diagnóstico , Nanomedicina Teranóstica/métodos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Antifúngicos/química , Células RAW 264.7 , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Camundongos Endogâmicos BALB C , Biomimética/métodos , Humanos , Azul de Metileno/química
18.
Nanoscale ; 16(12): 6095-6108, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38444228

RESUMO

In photothermal therapy (PTT), the photothermal conversion of the second near-infrared (NIR-II) window allows deeper penetration and higher laser irradiance and is considered a promising therapeutic strategy for deep tissues. Since cancer remains a leading cause of deaths worldwide, despite the numerous treatment options, we aimed to develop an improved bionic nanotheranostic for combined imaging and photothermal cancer therapy. We combined a gold nanobipyramid (Au NBP) as a photothermal agent and MnO2 as a magnetic resonance enhancer to produce core/shell structures (Au@MnO2; AM) and modified their surfaces with homologous cancer cell plasma membranes (PM) to enable tumour targeting. The performance of the resulting Au@MnO2@PM (AMP) nanotheranostic was evaluated in vitro and in vivo. AMP exhibits photothermal properties under NIR-II laser irradiation and has multimodal in vitro imaging functions. AMP enables the computed tomography (CT), photothermal imaging (PTI), and magnetic resonance imaging (MRI) of tumours. In particular, AMP exhibited a remarkable PTT effect on cancer cells in vitro and inhibited tumour cell growth under 1064 nm laser irradiation in vivo, with no significant systemic toxicity. This study achieved tumour therapy guided by multimodal imaging, thereby demonstrating a novel strategy for the use of bionic gold nanoparticles for tumour PTT under NIR-II laser irradiation.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Neoplasias , Humanos , Fototerapia/métodos , Terapia Fototérmica , Nanomedicina Teranóstica/métodos , Ouro/farmacologia , Compostos de Manganês/farmacologia , Compostos de Manganês/química , Biônica , Nanopartículas Metálicas/uso terapêutico , Óxidos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Imagem Multimodal/métodos , Linhagem Celular Tumoral
19.
Exp Neurol ; 376: 114757, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38508481

RESUMO

The intricate functional interactions between mitochondria and lysosomes play a pivotal role in maintaining cellular homeostasis and proper cellular functions. This dynamic interplay involves the exchange of molecules and signaling, impacting cellular metabolism, mitophagy, organellar dynamics, and cellular responses to stress. Dysregulation of these processes has been implicated in various neurodegenerative diseases. Additionally, mitochondrial-lysosomal crosstalk regulates the exosome release in neurons and glial cells. Under stress conditions, neurons and glial cells exhibit mitochondrial dysfunction and a fragmented network, which further leads to lysosomal dysfunction, thereby inhibiting autophagic flux and enhancing exosome release. This comprehensive review synthesizes current knowledge on mitochondrial regulation of cell death, organelle dynamics, and vesicle trafficking, emphasizing their significant contributions to neurodegenerative diseases. Furthermore, we explore the emerging field of nanomedicine in the management of neurodegenerative diseases. The review provides readers with an insightful overview of nano strategies that are currently advancing the mitochondrial-lysosome-extracellular vesicle axis as a therapeutic approach for mitigating neurodegenerative diseases.


Assuntos
Vesículas Extracelulares , Lisossomos , Mitocôndrias , Doenças Neurodegenerativas , Humanos , Lisossomos/metabolismo , Vesículas Extracelulares/metabolismo , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Mitocôndrias/metabolismo , Animais , Nanomedicina Teranóstica/métodos
20.
J Mater Chem B ; 12(15): 3569-3593, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38494982

RESUMO

In recent years, inorganic nanoparticles (NPs) have attracted increasing attention as potential theranostic agents in the field of oncology. Photothermal therapy (PTT) is a minimally invasive technique that uses nanoparticles to produce heat from light to kill cancer cells. PTT requires two essential elements: a photothermal agent (PTA) and near-infrared (NIR) radiation. The role of PTAs is to absorb NIR, which subsequently triggers hyperthermia within cancer cells. By raising the temperature in the tumor microenvironment (TME), PTT causes damage to the cancer cells. Nanoparticles (NPs) are instrumental in PTT given that they facilitate the passive and active targeting of the PTA to the TME, making them crucial for the effectiveness of the treatment. In addition, specific targeting can be achieved through their enhanced permeation and retention effect. Thus, owing to their significant advantages, such as altering the morphology and surface characteristics of nanocarriers comprised of PTA, NPs have been exploited to facilitate tumor regression significantly. This review highlights the properties of PTAs, the mechanism of PTT, and the results obtained from the improved curative efficacy of PTT by utilizing NPs platforms.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Humanos , Fototerapia/métodos , Hipertermia Induzida/métodos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nanomedicina Teranóstica/métodos , Microambiente Tumoral
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