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1.
Int J Nanomedicine ; 19: 6485-6497, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38946886

RESUMO

Angiogenesis is a physiological process of forming new blood vessels that has pathological importance in seemingly unrelated illnesses like cancer, diabetes, and various inflammatory diseases. Treatment targeting angiogenesis has shown promise for these types of diseases, but current anti-angiogenic agents have critical limitations in delivery and side-effects. This necessitates exploration of alternative approaches like biomolecule-based drugs. Proteins, lipids, and oligonucleotides have recently become popular in biomedicine, specifically as biocompatible components of therapeutic drugs. Their excellent bioavailability and potential bioactive and immunogenic properties make them prime candidates for drug discovery or drug delivery systems. Lipid-based liposomes have become standard vehicles for targeted nanoparticle (NP) delivery, while protein and nucleotide NPs show promise for environment-sensitive delivery as smart NPs. Their therapeutic applications have initially been hampered by short circulation times and difficulty of fabrication but recent developments in nanofabrication and NP engineering have found ways to circumvent these disadvantages, vastly improving the practicality of biomolecular NPs. In this review, we are going to briefly discuss how biomolecule-based NPs have improved anti-angiogenesis-based therapy.


Assuntos
Inibidores da Angiogênese , Neovascularização Patológica , Nanomedicina Teranóstica , Humanos , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/administração & dosagem , Nanomedicina Teranóstica/métodos , Neovascularização Patológica/tratamento farmacológico , Animais , Lipossomos/química , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Oligonucleotídeos/química , Oligonucleotídeos/administração & dosagem , Oligonucleotídeos/farmacocinética , Oligonucleotídeos/farmacologia , Proteínas/química , Proteínas/administração & dosagem , Lipídeos/química , Nanopartículas/química
2.
Nanotheranostics ; 8(4): 473-496, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38961885

RESUMO

Cardiotoxicity, the often-overlooked second leading cause of death in cancer patients, has been associated with certain anticancer drugs. These drugs can induce cardiac damage through various pathways, and their adverse effects on the heart are not fully understood. Cardiotoxicity is a major issue in cancer treatment, particularly with chemotherapeutics, because it can cause cardiac dysfunction such as hypotension, heart failure, and even death. Doxorubicin, 5-fluorouracil, and trastuzumab, all of which are very potent anticancer drugs, are known to cause cardiotoxicity. When it comes to lowering cardiotoxicity and alleviating the harmful effects of chemotherapy medications, nanomedicine has the potential to transport therapeutic molecules. Nanotheranostics offers novel options for identifying and treating cardiotoxicity resulting from a wide range of substances, including anticancer medications. Additionally, theranostics platforms such as micellar systems, carbon-based nanomedicine, solid lipid nanoparticles, polymeric nanoparticles, and liposomes can transport chemotherapeutic medications while minimising their cardiotoxicity. The present level of understanding of the molecular and cellular processes that lead to cardiotoxicity in reaction to both traditional chemotherapy and targeted drug delivery systems is summarised in this article. This review delves into nanomedicine and nanotheranostics, with an emphasis on reducing anticancer medication-induced cardiac toxicity. Nanotheranostics provide potential solutions for early diagnosis and tailored therapy of heart injury by combining diagnostic and therapeutic capabilities into nanomedicine.


Assuntos
Antineoplásicos , Cardiotoxicidade , Nanomedicina , Nanomedicina Teranóstica , Humanos , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Cardiotoxicidade/etiologia , Nanomedicina/métodos , Nanomedicina Teranóstica/métodos , Animais , Cardiopatias/induzido quimicamente , Neoplasias/tratamento farmacológico , Nanopartículas/química
3.
Theranostics ; 14(10): 3900-3908, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994024

RESUMO

Background: Osteoarthritis (OA) standing as the most prevalent form of arthritis, closely associates with heightened levels of reactive oxygen species, particularly hypochlorous acid (HOCl). Although there are numerous probes available for detecting HOCl in the OA region, probes with dual functions of diagnostic and therapeutic capabilities are still significantly lacking. While this type of probe can reduce the time gap between diagnosis and treatment, which is clinically needed. Methods: We developed a fluorescent probe (DHU-CBA1) toward HOCl with theranostics functions through the release of methylene blue (MB) and ibuprofen (IBP) in this work. DHU-CBA1 can detect HOCl with high specificity and sensitivity, releasing MB and IBP with an impressive efficiency of ≥ 95% in vitro. Results: DHU-CBA1 exhibits good biosafety, enabling in vivo imaging of endogenous HOCl, along with reducing arthritis scores, improving synovitis and cartilage damage, and maintaining catabolic balance while alleviating senescence in cartilage. Conclusions: This study proposes a novel approach to enhance osteoarthritis therapy by releasing IBP via a smart HOCl-enabled fluorescent probe.


Assuntos
Corantes Fluorescentes , Ácido Hipocloroso , Ibuprofeno , Azul de Metileno , Osteoartrite , Osteoartrite/tratamento farmacológico , Corantes Fluorescentes/química , Ibuprofeno/administração & dosagem , Animais , Azul de Metileno/química , Camundongos , Humanos , Nanomedicina Teranóstica/métodos , Masculino , Imagem Óptica/métodos , Espécies Reativas de Oxigênio/metabolismo
5.
Molecules ; 29(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38999044

RESUMO

BACKGROUND: FAP radiopharmaceuticals show promise for cancer diagnosis; however, their limited tumor residency hinders treatment. This study compared two FAPi derivatives, DOTA.SA.FAPi and DOTAGA.(SA.FAPi)2, labeled with gallium-68 and lutetium-177, aiming to determine an optimum combination for creating theranostic pairs. METHODS: The radiotracers were studied for lipophilicity, binding to human serum proteins, and binding to human cancer-associated fibroblasts (CAFs) in vitro, including saturation and internalization/externalization studies. PET/SPECT/CT and biodistribution studies were conducted in PC3 and U87MG xenografts for [68Ga]Ga-DOTA.SA.FAPi and [68Ga]Ga-DOTAGA.(SA.FAPi)2. [177Lu]Lu-DOTA.SA.FAPi and [177Lu]Lu-DOTAGA.(SA.FAPi)2, were evaluated in PC3 xenografts. Biodistribution studies of [68Ga]Ga-DOTA.SA.FAPi were performed in healthy male and female mice. RESULTS: All radiotracers exhibited strong binding to FAP. Their internalization rate was fast while only [177Lu]Lu-DOTAGA.(SA.FAPi)2 was retained longer in CAFs. [68Ga]Ga-DOTAGA.(SA.FAPi)2 and [177Lu]Lu-DOTAGA.(SA.FAPi)2 displayed elevated lipophilicity and affinity for human serum proteins compared to [68Ga]Ga-DOTA.SA.FAPi and [177Lu]Lu-DOTA.SA.FAPi. In vivo studies revealed slower washout of [68Ga]Ga-DOTAGA.(SA.FAPi)2 within 3 h compared to [68Ga]Ga-DOTA.SA.FAPi. The tumor-to-tissue ratios of [68Ga]Ga-DOTAGA.(SA.FAPi)2 versus [68Ga]Ga-DOTA.SA.FAPi did not exhibit any significant differences. [177Lu]Lu-DOTAGA.(SA.FAPi)2 maintained a significant tumor uptake even after 96 h p.i. compared to [177Lu]Lu-DOTA.SA.FAPi. CONCLUSIONS: Dimeric compounds hold promise for therapy, while monomers are better suited for diagnostics. Finding the right combination is essential for effective disease management.


Assuntos
Endopeptidases , Radioisótopos de Gálio , Lutécio , Radioisótopos , Compostos Radiofarmacêuticos , Lutécio/química , Humanos , Animais , Camundongos , Distribuição Tecidual , Radioisótopos/química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/farmacologia , Radioisótopos de Gálio/química , Linhagem Celular Tumoral , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/metabolismo , Gelatinases/antagonistas & inibidores , Gelatinases/metabolismo , Compostos Heterocíclicos com 1 Anel/química , Feminino , Masculino , Nanomedicina Teranóstica
6.
Molecules ; 29(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38999115

RESUMO

According to the World Health Organization (WHO) and the International Agency for Research on Cancer (IARC), the number of cancer cases and deaths worldwide is predicted to nearly double by 2030, reaching 21.7 million cases and 13 million fatalities. The increase in cancer mortality is due to limitations in the diagnosis and treatment options that are currently available. The close relationship between diagnostics and medicine has made it possible for cancer patients to receive precise diagnoses and individualized care. This article discusses newly developed compounds with potential for photodynamic therapy and diagnostic applications, as well as those already in use. In addition, it discusses the use of artificial intelligence in the analysis of diagnostic images obtained using, among other things, theranostic agents.


Assuntos
Inteligência Artificial , Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/diagnóstico , Neoplasias/terapia , Fotoquimioterapia/métodos , Nanomedicina Teranóstica/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia
7.
Mikrochim Acta ; 191(7): 433, 2024 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951214

RESUMO

A cancer-targeted glutathione (GSH)-gated theranostic probe (CGT probe) for intracellular miRNA imaging and combined treatment of self-sufficient starvation therapy (ST) and chemodynamic therapy (CDT) was developed. The CGT probe is constructed using MnO2 nanosheet (MS) as carrier material to adsorb the elaborately designed functional DNAs. It can be internalized by cancer cells via specific recognition between the AS1411 aptamer and nucleolin. After CGT probe entering the cancer cells, the overexpressed GSH, as gate-control, can degrade MS to Mn2+ which can be used for CDT by Fenton-like reaction. Simultaneously, Mn2+-mediated CDT can further cascade with the enzyme-like activities (catalase-like activity and glucose oxidase-like activity) of CGT probe, achieving self-sufficient ST/CDT synergistic therapy. Meanwhile, the anchored DNAs are released, achieving in situ signal amplification via disubstituted-catalytic hairpin assembly (DCHA) and FRET (fluorescence resonance energy transfer) imaging of miR-21. The in vitro and in vivo experiments demonstrated that accurate and sensitive miRNA detection can be achieved using the CGT probe. Overall, the ingenious CGT probe opens a new avenue for the development of early clinical diagnosis and cancer therapy.


Assuntos
Transferência Ressonante de Energia de Fluorescência , Glutationa , Compostos de Manganês , MicroRNAs , Óxidos , Humanos , Glutationa/química , Glutationa/metabolismo , Animais , Compostos de Manganês/química , Óxidos/química , Aptâmeros de Nucleotídeos/química , Camundongos , Camundongos Nus , Nanomedicina Teranóstica/métodos , Nucleolina , Neoplasias/diagnóstico por imagem , Nanoestruturas/química , Oligodesoxirribonucleotídeos/química , Camundongos Endogâmicos BALB C , Corantes Fluorescentes/química
8.
ACS Appl Mater Interfaces ; 16(28): 35925-35935, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38950334

RESUMO

The development of efficient theranostic nanoagents for the precise diagnosis and targeted therapy of glioblastoma (GBM) remains a big challenge. Herein, we designed and developed porphyrin-based organic nanoparticles (PNP NPs) with strong emission in the near-infrared IIa window (NIR-IIa) for orthotopic GBM theranostics. PNP NPs possess favorable photoacoustic and photothermal properties, high photostability, and low toxicity. After modification with the RGD peptide, the obtained PNPD NPs exhibited enhanced blood-brain barrier (BBB) penetration capability and GBM targeting ability. NIR-IIa imaging was employed to monitor the in vivo biodistribution and accumulation of the nanoparticles, revealing a significant enhancement in penetration depth and signal-to-noise ratio. Both in vitro and in vivo results demonstrated that PNPD NPs effectively inhibited the proliferation of tumor cells and induced negligible side effects in normal brain tissues. In general, the work presented a kind of brain-targeted porphyrin-based NPs with NIR-IIa fluorescence for orthotopic glioblastoma theranostics, showing promising prospects for clinical translation.


Assuntos
Glioblastoma , Nanopartículas , Porfirinas , Nanomedicina Teranóstica , Glioblastoma/diagnóstico por imagem , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/metabolismo , Animais , Nanopartículas/química , Humanos , Porfirinas/química , Porfirinas/farmacologia , Camundongos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Raios Infravermelhos , Distribuição Tecidual , Barreira Hematoencefálica/metabolismo , Camundongos Nus , Antineoplásicos/química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Fluorescência
9.
Med Oncol ; 41(8): 205, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037549

RESUMO

In this study, we developed new gadolinium-graphene quantum dot nanoparticles (Gd-GQDs) as a theranostic platform for magnetic resonance imaging and improved the efficiency of radiotherapy in HPV-positive oropharyngeal cancer. Based on cell toxicity results, Gd-GQD NPs were nontoxic for both cancer and normal cell lines up to 25 µg/ml. These NPs enhance the cytotoxic effect of radiation only on cancer cells but not on normal cells. The flow cytometry analysis indicated that cell death mainly occurred in the late phase of apoptosis. The immunocytochemical analysis was used to evaluate apoptosis pathway proteins. The Bcl-2 and p53 protein levels did not differ statistically significantly between radiation alone group and those that received irradiation in combination with NPs. In contrast, the combination group exhibited a significant increase in Bax protein expression, suggesting that cells could undergo apoptosis independent of the p53 pathway. Magnetic resonance (MR) imaging showed that Gd-GQD NPs, when used at low concentrations, enhanced T1-weighted signal intensity resulting from T1 shortening effects. At higher concentrations, the T2 shortening effect became predominant and was able to decrease the signal intensity. Gd-GQD appears to offer a novel approach for enhancing the effectiveness of radiation treatment and facilitating MR imaging for monitoring HPV-positive tumors.


Assuntos
Gadolínio , Imageamento por Ressonância Magnética , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Pontos Quânticos , Humanos , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/radioterapia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Imageamento por Ressonância Magnética/métodos , Apoptose/efeitos dos fármacos , Nanomedicina Teranóstica/métodos , Linhagem Celular Tumoral
10.
ACS Nano ; 18(28): 18230-18245, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38950337

RESUMO

Therapy-induced modulation of the tumor microenvironment (TME) to overcome the immunosuppressive TME is considered to be an opportunity for cancer treatment. However, monitoring of TME modulation during the therapeutic process to accurately determine immune responses and adjust treatment plans in a timely manner remains to be challenging. Herein, we report a carrier-free nanotheranostic system (CANPs) assembled by two boron dipyrromethene (BODIPY) dyes, a sonophotosensitizer C-BDP, and a nitric oxide (NO) probe amino-BODIPY (A-BDP). CANPs can exert combined sonophototherapeutic effects of C-BDP under ultrasound and light irradiation and simultaneously induce inflammatory TME, as well as emit bright fluorescence via A-BDP by monitoring tumor-associated macrophages (TAMs) repolarization through the released NO in vitro and in vivo. Of note, transforming growth factor-ß (TGF-ß) could be the key cytokine involved in the sonophototherapy-induced TME reprogramming. By virtue of high physiological stability, good biocompatibility, and effective tumor targetability, CANPs could be a potential nanotheranostic system for the simultaneous induction and detection of TME reprogramming triggered by sonophototherapy.


Assuntos
Nanomedicina Teranóstica , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Animais , Camundongos , Porfobilinogênio/análogos & derivados , Porfobilinogênio/química , Porfobilinogênio/farmacologia , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Compostos de Boro/química , Compostos de Boro/farmacologia , Óxido Nítrico/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Feminino , Nanopartículas/química , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Células RAW 264.7
11.
Theranostics ; 14(9): 3634-3652, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948059

RESUMO

Rationale: Molecular imaging of microenvironment by hypoxia-activatable fluorescence probes has emerged as an attractive approach to tumor diagnosis and image-guided treatment. Difficulties remain in its translational applications due to hypoxia heterogeneity in tumor microenvironments, making it challenging to image hypoxia as a reliable proxy of tumor distribution. Methods: We report a modularized theranostics platform to fluorescently visualize hypoxia via light-modulated signal compensation to overcome tumor heterogeneity, thereby serving as a diagnostic tool for image-guided surgical resection and photodynamic therapy. Specifically, the platform integrating dual modules of fluorescence indicator and photodynamic moderator using supramolecular host-guest self-assembly, which operates cooperatively as a cascaded "AND" logic gate. First, tumor enrichment and specific fluorescence turn-on in hypoxic regions were accessible via tumor receptors and cascaded microenvironment signals as simultaneous inputs of the "AND" gate. Second, image guidance by a lighted fluorescence module and light-mediated endogenous oxygen consumption of a photodynamic module as dual inputs of "AND" gate collaboratively enabled light-modulated signal compensation in situ, indicating homogeneity of enhanced hypoxia-related fluorescence signals throughout a tumor. Results: In in vitro and in vivo analyses, the biocompatible platform demonstrated several strengths including a capacity for dual tumor targeting to progressively facilitate specific fluorescence turn-on, selective signal compensation, imaging-time window extension conducive to precise normalized image-guided treatment, and the functionality of tumor glutathione depletion to improve photodynamic efficacy. Conclusion: The hypoxia-activatable, image-guided theranostic platform demonstrated excellent potential for overcoming hypoxia heterogeneity in tumors.


Assuntos
Imagem Óptica , Nanomedicina Teranóstica , Animais , Nanomedicina Teranóstica/métodos , Humanos , Imagem Óptica/métodos , Camundongos , Microambiente Tumoral , Linhagem Celular Tumoral , Corantes Fluorescentes/química , Fotoquimioterapia/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Camundongos Nus , Cirurgia Assistida por Computador/métodos
12.
Biomater Sci ; 12(15): 3805-3825, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38967109

RESUMO

Stimulus-responsive polymers have found widespread use in biomedicine due to their ability to alter their own structure in response to various stimuli, including internal factors such as pH, reactive oxygen species (ROS), and enzymes, as well as external factors like light. In the context of atherosclerotic cardiovascular diseases (CVDs), stimulus-response polymers have been extensively employed for the preparation of smart nanocarriers that can deliver therapeutic and diagnostic drugs specifically to inflammatory lesions. Compared with traditional drug delivery systems, stimulus-responsive nanosystems offer higher sensitivity, greater versatility, wider applicability, and enhanced biosafety. Recent research has made significant contributions towards designing stimulus-responsive polymer nanosystems for CVDs diagnosis and treatment. This review summarizes recent advances in this field by classifying stimulus-responsive polymer nanocarriers according to different responsiveness types and describing numerous stimuli relevant to these materials. Additionally, we discuss various applications of stimulus-responsive polymer nanomaterials in CVDs theranostics. We hope that this review will provide valuable insights into optimizing the design of stimulus-response polymers for accelerating their clinical application in diagnosing and treating CVDs.


Assuntos
Doenças Cardiovasculares , Nanomedicina Teranóstica , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/terapia , Doenças Cardiovasculares/tratamento farmacológico , Animais , Polímeros/química , Polímeros Responsivos a Estímulos/química , Espécies Reativas de Oxigênio/metabolismo , Portadores de Fármacos/química , Nanoestruturas/química , Nanopartículas/química , Concentração de Íons de Hidrogênio
13.
Adv Colloid Interface Sci ; 330: 103207, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38843699

RESUMO

To overcome the challenges of poor wound diagnosis and limited clinical efficacy of current wound management, wound dressing materials with the aim of monitoring various biomarkers vital to the wound healing process such as temperature, pH, glucose concentration, and reactive oxygen species (ROS) and improving the therapeutic outcomes have been developed. These innovative theranostic dressings are smartly engineered using stimuli-responsive biomaterials to monitor and regulate local microenvironments and deliver cargos to the wound sites in a timely and effective manner. This review provides an overview of recent advances in novel theranostics for wound monitoring and therapy as well as giving insights into the future treatment of wounds via smart design of theranostic materials.


Assuntos
Nanomedicina Teranóstica , Cicatrização , Humanos , Cicatrização/efeitos dos fármacos , Bandagens , Concentração de Íons de Hidrogênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Materiais Biocompatíveis/química
14.
J Nucl Med ; 65(7): 1087-1094, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38844360

RESUMO

Benchtop 99Mo/99mTc and 188W/188Re generators enable economical production of molecular theranostic 99mTc and 188Re radiopharmaceuticals, provided that simple, kit-based chemistry exists to radiolabel targeting vectors with these radionuclides. We have previously described a diphosphine platform that efficiently incorporates 99mTc into receptor-targeted peptides. Here, we report its application to label a prostate-specific membrane antigen (PSMA)-targeted peptide with 99mTc and 188Re for diagnostic imaging and systemic radiotherapy of prostate cancer. Methods: Two diphosphine-dipeptide bioconjugates, DP1-PSMAt and DP2-PSMAt, were formulated into kits for radiolabeling with 99mTc and 188Re. The resulting radiotracers were studied in vitro, in prostate cancer cells, and in vivo in mouse xenograft models, to assess similarity of uptake and biodistribution for each 99mTc/188Re pair of agents. Results: Both DP1-PSMAt and DP2-PSMAt could be efficiently radiolabeled with 99mTc and 188Re using kit-based methods to furnish the isostructural compounds M-DP1-PSMAt and M-DP2-PSMAt (M = [99mTc]Tc, [188Re]Re). All 99mTc/188Re radiotracers demonstrated specific uptake in PSMA-expressing prostate cancer cells, with negligible uptake in prostate cancer cells that did not express PSMA or in which PSMA uptake was blocked. M-DP1-PSMAt and M-DP2-PSMAt also exhibited high tumor uptake (18-30 percentage injected dose per gram at 2 h after injection), low retention in nontarget organs, fast blood clearance, and excretion predominantly via a renal pathway. Importantly, each pair of 99mTc/188Re radiotracers showed near-identical biologic behavior in these experiments. Conclusion: We have prepared and developed novel pairs of isostructural PSMA-targeting 99mTc/188Re theranostic agents. These generator-based theranostic agents have potential to provide access to the benefits of PSMA-targeted diagnostic imaging and systemic radiotherapy in health care settings that do not routinely have access to either reactor-produced 177Lu radiopharmaceuticals or PET/CT infrastructure.


Assuntos
Neoplasias da Próstata , Radioisótopos , Rênio , Tecnécio , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/metabolismo , Camundongos , Rênio/química , Animais , Humanos , Tecnécio/química , Radioisótopos/química , Linhagem Celular Tumoral , Distribuição Tecidual , Glutamato Carboxipeptidase II/metabolismo , Antígenos de Superfície/metabolismo , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Nanomedicina Teranóstica , Peptídeos/química , Medicina de Precisão
15.
Molecules ; 29(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38930939

RESUMO

Atherosclerosis continues to be a leading cause of morbidity and mortality globally. The precise evaluation of the extent of an atherosclerotic plaque is essential for forecasting its likelihood of causing health concerns and tracking treatment outcomes. When compared to conventional methods used, nanoparticles offer clear benefits and excellent development opportunities for the detection and characterisation of susceptible atherosclerotic plaques. In this review, we analyse the recent advancements of nanoparticles as theranostics in the management of atherosclerosis, with an emphasis on applications in drug delivery. Furthermore, the main issues that must be resolved in order to advance clinical utility and future developments of NP research are discussed. It is anticipated that medical NPs will develop into complex and advanced next-generation nanobotics that can carry out a variety of functions in the bloodstream.


Assuntos
Aterosclerose , Sistemas de Liberação de Medicamentos , Nanopartículas , Humanos , Aterosclerose/tratamento farmacológico , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Animais , Nanomedicina Teranóstica/métodos , Placa Aterosclerótica/tratamento farmacológico , Portadores de Fármacos/química
16.
J Mater Chem B ; 12(25): 6257-6274, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38845545

RESUMO

Despite enormous advancements in its management, cancer is the world's primary cause of mortality. Therefore, tremendous strides were made to produce intelligent theranostics with mitigated side effects and improved specificity and efficiency. Thus, we developed a pH-sensitive theranostic platform composed of dextran immobilized zinc oxide nanoparticles, loaded with doxorubicin and radiolabeled with the technetium-99m radionuclide (99mTc-labelled DOX-loaded ZnO@dextran). The platform measured 11.5 nm in diameter with -12 mV zeta potential, 88% DOX loading efficiency and 98.5% radiolabeling efficiency. It showed DOX release in a pH-responsive manner, releasing 93.1% cumulatively at pH 5 but just 7% at pH 7.4. It showed improved intracellular uptake, which resulted in a high growth suppressive effect against MCF-7 cancer cells as compared to the free DOX. It boasted a 4 times lower IC50 than DOX, indicating its significant anti-proliferative potential (0.14 and 0.55 µg ml-1, respectively). The in vitro biological evaluation revealed that its molecular mode of anti-proliferative action included downregulating Cdk-2, which provoked G1/S cell cycle arrest, and upregulating both the intracellular ROS level and caspase-3, which induced apoptosis and necrosis. The in vivo experiments in Ehrlich-ascites carcinoma bearing mice demonstrated that DOX-loaded ZnO@dextran showed a considerable 4-fold increase in anti-tumor efficacy compared to DOX. Moreover, by utilizing the diagnostic radionuclide (99mTc), the radiolabeled platform (99mTc-labelled DOX-loaded ZnO@dextran) was in vivo monitored in tumor-bearing mice, revealing high tumor accumulation (14% ID g-1 at 1 h p.i.) and reduced uptake in non-target organs with a 17.5 T/NT ratio at 1 h p.i. Hence, 99mTc-labelled DOX-loaded ZnO@dextran could be recommended as a rectified tumor-targeted theranostic platform.


Assuntos
Apoptose , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Doxorrubicina , Nanomedicina Teranóstica , Óxido de Zinco , Doxorrubicina/farmacologia , Doxorrubicina/química , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Humanos , Animais , Apoptose/efeitos dos fármacos , Camundongos , Concentração de Íons de Hidrogênio , Proliferação de Células/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Células MCF-7 , Nanopartículas/química , Distribuição Tecidual , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Dextranos/química , Portadores de Fármacos/química , Tecnécio/química , Tamanho da Partícula
17.
Nanoscale ; 16(24): 11411-11428, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38860512

RESUMO

The repurposing of existing drugs, referred to as theranostics, has made profound impacts on precision medicine. Indocyanine green (ICG), a well-established and clinical dye, has continued to be a star agent, described as a multifunctional molecule with concurrent photo- or sono-sensitiveness capabilities and co-delivery accessibility, showing remarkable potential in the area of unimodal or multimodal imaging-guided therapy of various diseases, leading to the extensive consideration of immediate clinical translations. In this review, we strive to bring the understanding of repurposing performance assessment for ICG into practice by clarifying the relationships between its features and applicability. Specifically, we address the obstacles encountered in the process of developing an ICG repurposing strategy, as well as the noteworthy advancements made in the field of ICG repurposing. We also go into detail about the structure-function correlations of drugs containing ICG and how different structural groups significantly affect the physicochemical properties.


Assuntos
Reposicionamento de Medicamentos , Verde de Indocianina , Verde de Indocianina/química , Humanos , Animais , Nanomedicina Teranóstica , Corantes/química
18.
J Mater Sci Mater Med ; 35(1): 32, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896160

RESUMO

This study leverages nanotechnology by encapsulating indocyanine green (ICG) and paclitaxel (Tax) using zeolitic imidazolate frameworks-8 (ZIF-8) as a scaffold. This study aims to investigate the chemo-photothermal therapeutic potential of ZIF-8@ICG@Tax nanoparticles (NPs) in the treatment of non-small cell lung cancer (NSCLC). An "all-in-one" theranostic ZIF-8@ICG@Tax NPs was conducted by self-assembly based on electrostatic interaction. First, the photothermal effect, stability, pH responsiveness, drug release, and blood compatibility of ZIF-8@ICG@Tax were evaluated through in vitro testing. Furthermore, the hepatic and renal toxicity of ZIF-8@ICG@Tax were assessed through in vivo testing. Additionally, the anticancer effects of these nanoparticles were investigated both in vitro and in vivo. Uniform and stable chemo-photothermal ZIF-8@ICG@Tax NPs had been successfully synthesized and had outstanding drug releasing capacities. Moreover, ZIF-8@ICG@Tax NPs showed remarkable responsiveness dependent both on pH in the tumor microenvironment and NIR irradiation, allowing for targeted drug delivery and controlled drug release. NIR irradiation can enhance the tumor cell response to ZIF-8@ICG@Tax uptake, thereby promoting the anti-tumor growth in vitro and in vivo. ZIF-8@ICG@Tax and NIR irradiation have demonstrated remarkable synergistic anti-tumor growth properties compared to their individual components. This novel theranostic chemo-photothermal NPs hold great potential as a viable treatment option for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Liberação Controlada de Fármacos , Verde de Indocianina , Neoplasias Pulmonares , Nanopartículas , Paclitaxel , Nanomedicina Teranóstica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Verde de Indocianina/química , Humanos , Animais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Concentração de Íons de Hidrogênio , Nanopartículas/química , Nanomedicina Teranóstica/métodos , Paclitaxel/química , Paclitaxel/farmacologia , Camundongos , Zeolitas/química , Raios Infravermelhos , Fototerapia/métodos , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Células A549 , Estruturas Metalorgânicas/química , Camundongos Nus , Sistemas de Liberação de Medicamentos , Imidazóis
19.
Int J Nanomedicine ; 19: 5479-5492, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863646

RESUMO

Background: In recent years, PD-L1 has been primarily utilized as an immune checkpoint marker in cancer immunotherapy. However, due to tumor heterogeneity, the response rate to such therapies often falls short of expectations. In addition to its role in immunotherapy, PD-L1 serves as a specific target on the surface of tumor cells for targeted diagnostic and therapeutic interventions. There is an absence of a fully developed PD-L1-targeted diagnostic and therapeutic probe for clinical use, which constrains the exploration and clinical exploitation of this target. Methods and Results: In this study, we engineered a PD-L1-targeted probe with multimodal imaging and dual therapeutic functionalities utilizing organic melanin nanoparticles. Functionalization with the WL12-SH peptide endowed the nanoprobe with specific targeting capabilities. Subsequent radiolabeling with 89Zr (half-life: 100.8 hours) and chelation of Mn2+ ions afforded the probe the capacity for simultaneous PET and MRI imaging modalities. Cellular uptake assays revealed pronounced specificity, with -positive cells exhibiting significantly higher uptake than -negative counterparts (p < 0.05). Dual-modal PET/MRI imaging delineated rapid and sustained accumulation at the neoplastic site, yielding tumor-to-non-tumor (T/NT) signal ratios at 24 hours post-injection of 16.67±3.45 for PET and 6.63±0.64 for MRI, respectively. We conjugated the therapeutic radionuclide 131I (half-life: 8.02 days) to the construct and combined low-dose radiotherapy and photothermal treatment (PTT), culminating in superior antitumor efficacy while preserving a high safety profile. The tumors in the cohort receiving the dual-modality therapy exhibited significantly reduced volume and weight compared to those in the control and monotherapy groups. Conclusion: We developed and applied a novel -targeted multimodal theranostic nanoprobe, characterized by its high specificity and superior imaging capabilities as demonstrated in PET/MRI modalities. Furthermore, this nanoprobe facilitates potent therapeutic efficacy at lower radionuclide doses when used in conjunction with PTT.


Assuntos
Antígeno B7-H1 , Imageamento por Ressonância Magnética , Imagem Multimodal , Nanopartículas , Tomografia por Emissão de Pósitrons , Nanomedicina Teranóstica , Nanomedicina Teranóstica/métodos , Animais , Antígeno B7-H1/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Nanopartículas/química , Humanos , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Linhagem Celular Tumoral , Camundongos , Melaninas/química , Zircônio/química , Radioisótopos/química , Feminino , Imunoterapia/métodos
20.
J Control Release ; 371: 429-444, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38849096

RESUMO

Protein-based nanoparticles have garnered significant attention in theranostic applications due to their superior biocompatibility, exceptional biodegradability and ease of functionality. Compared to other nanocarriers, protein-based nanoparticles offer additional advantages, including biofunctionality and precise molecular recognition abilities, which make them highly effective in navigating complex biological environments. Moreover, proteins can serve as powerful tools with self-assembling structures and reagents that enhance cell penetration. And their derivation from abundant renewable sources and ability to degrade into harmless amino acids further enhance their suitability for biomedical applications. However, protein-based nanoparticles have so far not realized their full potential. In this review, we summarize recent advances in the use of protein nanoparticles in tumor diagnosis and treatment and outline typical methods for preparing protein nanoparticles. The review of protein nanoparticles may provide useful new insights into the development of biomaterial fabrication.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas , Neoplasias , Proteínas , Nanomedicina Teranóstica , Humanos , Neoplasias/tratamento farmacológico , Nanomedicina Teranóstica/métodos , Nanopartículas/química , Animais , Proteínas/administração & dosagem , Proteínas/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química
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