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1.
Nanoscale ; 16(21): 10208-10220, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38727407

RESUMO

Immune activation, whether occurring from direct immune checkpoint blockade or indirectly as a result of chemotherapy, is an approach that has drastically impacted the way we treat cancer. Utilizing patients' own immune systems for anti-tumor efficacy has been translated to robust immunotherapies; however, clinically significant successes have been achieved in only a subset of patient populations. Dendrimers and dendritic polymers have recently emerged as a potential nanocarrier platform that significantly improves the therapeutic efficacy of current and next-generation cancer immunotherapies. In this paper, we highlight the recent progress in developing dendritic polymer-based therapeutics with immune-modulating properties. Specifically, dendrimers, dendrimer hybrids, and dendronized copolymers have demonstrated promising results and are currently in pre-clinical development. Despite their early stage of development, these nanocarriers hold immense potential to make profound impact on cancer immunotherapy and combination therapy. This overview provides insights into the potential impact of dendrimers and dendron-based polymers, offering a preview of their potential utilities for various aspects of cancer treatment.


Assuntos
Dendrímeros , Imunoterapia , Nanopartículas , Neoplasias , Humanos , Dendrímeros/química , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Nanopartículas/química , Nanopartículas/uso terapêutico , Animais , Portadores de Fármacos/química , Polímeros/química
2.
Nanotechnology ; 35(33)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38749415

RESUMO

Candida auris, a rapidly emerging multidrug-resistant fungal pathogen, poses a global health threat, with cases reported in over 47 countries. Conventional detection methods struggle, and the increasing resistance ofC. auristo antifungal agents has limited treatment options. Nanoparticle-based therapies, utilizing materials like silver, carbon, zinc oxide, titanium dioxide, polymer, and gold, show promise in effectively treating cutaneous candidiasis. This review explores recent advancements in nanoparticle-based therapies, emphasizing their potential to revolutionize antifungal therapy, particularly in combatingC. aurisinfections. The discussion delves into mechanisms of action, combinations of nanomaterials, and their application against multidrug-resistant fungal pathogens, offering exciting prospects for improved clinical outcomes and reduced mortality rates. The aim is to inspire further research, ushering in a new era in the fight against multidrug-resistant fungal infections, paving the way for more effective and targeted therapeutic interventions.


Assuntos
Antifúngicos , Candidíase , Farmacorresistência Fúngica Múltipla , Nanopartículas , Humanos , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Candidíase/tratamento farmacológico , Nanopartículas/química , Nanopartículas/uso terapêutico , Candida auris/efeitos dos fármacos , Animais , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico
3.
ACS Appl Mater Interfaces ; 16(20): 25879-25891, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38718301

RESUMO

Biological imaging-guided targeted tumor therapy has been a soughtafter goal in the field of cancer diagnosis and treatment. To this end, we proposed a strategy to modulate surface plasmon resonance and endow WO3-x nanoparticles (NPs) with enzyme-like catalytic properties by doping Fe2+ in the structure of the NPs. Doping of the Fe2+ introduced oxygen vacancies into the structure of the NPs, inducing a red shift of the maximum absorption wavelength into the near-infrared II (NIR-II) region and enhancing the photoacoustic (PA) and photothermal properties of the NPs for more effective imaging-guided cancer therapy. Under NIR-II laser irradiation, the Fe-WO3-x NPs produced very strong NIR-II PA and photothermal effects, which significantly enhanced the PA imaging and photothermal treatment effects. On the other hand, Fe2+ in Fe-WO3-x could undergo Fenton reactions with H2O2 in the tumor tissue to generate ·OH for chemodynamic therapy. In addition, Fe-WO3-x can also catalyze the above reactions to produce more reactive oxygen species (ROS) and induce the oxidation of NADH to interfere with intracellular adenosine triphosphate (ATP) synthesis, thereby further improving the efficiency of cancer therapy. Specific imaging of tumor tissue and targeted synergistic therapy was achieved after ligation of a MUC1 aptamer to the surface of the Fe-WO3-x NPs by the complexing of -COOH in MUC1 with tungsten ions on the surface of the NPs. These results demonstrated that Fe-WO3-x NPs could be a promising diagnosis and therapeutic agent for cancer. Such a study opens up new avenues into the rational design of nanodiagnosis and treatment agents for NIR-II PA imaging and cancer therapy.


Assuntos
Técnicas Fotoacústicas , Ressonância de Plasmônio de Superfície , Tungstênio , Animais , Humanos , Camundongos , Tungstênio/química , Raios Infravermelhos , Óxidos/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Nanopartículas/química , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo
4.
ACS Appl Mater Interfaces ; 16(20): 26590-26603, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38742307

RESUMO

Photodynamic therapy (PDT) based on upconversion nanoparticles (UCNPs) has been widely used in the treatment of a variety of tumors. Compared with other therapeutic methods, this treatment has the advantages of high efficiency, strong penetration, and controllable treatment range. PDT kills tumors by generating a large amount of reactive oxygen species (ROS), which causes oxidative stress in the tumor. However, this killing effect is significantly inhibited by the tumor's own resistance to ROS. This is because tumors can either deplete ROS by high concentration of glutathione (GSH) or stimulate autophagy to eliminate ROS-generated damage. Furthermore, the tumor can also consume ROS through the lactic acid metabolic pathway, ultimately hindering therapeutic progress. To address this conundrum, we developed a UCNP-based nanocomposite for enhanced PDT by reducing tumor ROS resistance. First, Ce6-doped SiO2 encapsulated UCNPs to ensure the efficient energy transfer between UCNPs and Ce6. Then, the biodegradable tetrasulfide bond-bridged mesoporous organosilicon (MON) was coated on the outer layer to load chloroquine (CQ) and α-cyano4-hydroxycinnamic acid (CHCA). Finally, hyaluronic acid was utilized to modify the nanomaterials to realize an active-targeting ability. The obtained final product was abbreviated as UCNPs@MON@CQ/CHCA@HA. Under 980 nm laser irradiation, upconverted red light from UCNPs excited Ce6 to produce a large amount of singlet oxygen (1O2), thus achieving efficient PDT. The loaded CQ and CHCA in MON achieved multichannel enhancement of PDT. Specifically, CQ blocked the autophagy process of tumor cells, and CHCA inhibited the uptake of lactic acid by tumor cells. In addition, the coated MON consumed a high level of intracellular GSH. In this way, these three functions complemented each other, just as the "three musketeers" punctured ROS resistance in tumors from multiple angles, and both in vitro and in vivo experiments had demonstrated the elevated PDT efficacy of nanomaterials.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Animais , Humanos , Camundongos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Dióxido de Silício/química , Cloroquina/farmacologia , Cloroquina/química , Camundongos Endogâmicos BALB C
5.
Nanoscale ; 16(20): 9953-9965, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38693876

RESUMO

Sonodynamic therapy (SDT) is an advanced non-invasive cancer treatment strategy with moderate tissue penetration, less invasiveness and a reliable curative effect. However, due to the low stability, potential bio-toxicity and lack of tumor targeting capability of most sonosensitizers, the vast clinical application of SDT has been challenging and limited. Therefore, it is desirable to develop a novel approach to implement sonosensitizers to SDT for cancer treatments. In this study, an amphiphilic polypeptide was designed to effectively encapsulate rose bengal (RB) as a model sonosensitizer to form peptido-nanomicelles (REPNs). The as-fabricated REPNs demonstrated satisfactory tumor targeting and fluorescence performances, which made them superb imaging tracers in vivo. In the meantime, they generated considerable amounts of reactive oxygen species (ROS) to promote tumor cell apoptosis under ultrasound irradiation and showed excellent anti-tumor performance without obvious side effects. These engineered nanomicelles in combination with medical ultrasound may be used to achieve integrin αvß3-targeted sonodynamic therapy against breast cancer, and it is also a promising non-invasive cancer treatment strategy for clinical translations.


Assuntos
Neoplasias da Mama , Integrina alfaVbeta3 , Micelas , Peptídeos , Espécies Reativas de Oxigênio , Terapia por Ultrassom , Integrina alfaVbeta3/metabolismo , Feminino , Peptídeos/química , Peptídeos/farmacologia , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Rosa Bengala/química , Rosa Bengala/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico
6.
Biomater Adv ; 161: 213891, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38781738

RESUMO

An antitumour chemo-photodynamic therapy nanoplatform was constructed based on phospholipid-coated NaYF4: Yb/Er upconversion nanoparticles (UCNPs). In this work, the amphiphilic block copolymer DSPE-PEG2000 was combined with the surface ligand oleic acid of the UCNPs through hydrophobic interaction to form liposomes with a dense hydrophobic layer in which the photosensitizer hypocrellin B (HB) was assembled. The coated HB formed J-aggregates, which caused a large redshift in the absorption spectrum and improved the quantum efficiency of energy transfer. Furthermore, MnO2 nanosheets grew in-situ on the liposomes through OMn coordination. Therefore, a multifunctional tumour microenvironment (TME)-responsive theranostic nanoplatform integrating photodynamic therapy (PDT) and chemodynamic therapy (CDT) was successfully developed. The results showed that this NIR-mediated chemo-photodynamic therapy nanoplatform was highly efficient for oncotherapy.


Assuntos
Compostos de Manganês , Nanopartículas , Óxidos , Perileno , Fotoquimioterapia , Fármacos Fotossensibilizantes , Quinonas , Fotoquimioterapia/métodos , Perileno/análogos & derivados , Perileno/farmacologia , Perileno/química , Perileno/administração & dosagem , Humanos , Quinonas/química , Quinonas/farmacologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Óxidos/química , Óxidos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/administração & dosagem , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Animais , Fenol/química , Fenol/farmacologia , Lipossomos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Camundongos , Linhagem Celular Tumoral , Microambiente Tumoral/efeitos dos fármacos
7.
Biosens Bioelectron ; 259: 116424, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38801792

RESUMO

Phototherapy has garnered significant attention in the past decade. Photothermal and photodynamic synergistic therapy combined with NIR fluorescence imaging has been one of the most attractive treatment options because of the deep tissue penetration, high selectivity and excellent therapeutic effect. Benefiting from the superb photometrics and ease of modification, perylene diimide (PDI) and its derivatives have been employed as sensing probes and therapeutic agents in the biological and biomedical research fields, and exhibiting excellent potential. Herein, we reported the development of a novel organic small-molecule phototherapeutic agent, PDI-TN. The absorption of PDI-TN extends into the NIR region, which provides feasibility for NIR phototherapy. PDI-TN overcomes the traditional Aggregation-Caused Quenching (ACQ) effect and exhibits typical characteristics of Aggregation-Induced Emission (AIE). Subsequently, PDI-TN NPs were obtained by using an amphiphilic triblock copolymer F127 to encapsulate PDI-TN. Interestingly, the PDI-TN NPs not only exhibit satisfactory photothermal effects, but also can generate O2•- and 1O2 through type I and type II pathways, respectively. Additionally, the PDI-TN NPs emit strong fluorescence in the NIR-II region, and show outstanding therapeutic potential for in vivo NIR-II fluorescence imaging. To our knowledge, PDI-TN is the first PDI derivative used for NIR-II fluorescence imaging-guided photodynamic and photothermal synergistic therapy, which suggests excellent potential for future biological/biomedical applications.


Assuntos
Imidas , Imagem Óptica , Perileno , Fotoquimioterapia , Perileno/análogos & derivados , Perileno/química , Perileno/farmacologia , Perileno/uso terapêutico , Imidas/química , Imidas/uso terapêutico , Fotoquimioterapia/métodos , Humanos , Imagem Óptica/métodos , Animais , Camundongos , Corantes Fluorescentes/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Terapia Fototérmica , Raios Infravermelhos , Linhagem Celular Tumoral
8.
ACS Appl Mater Interfaces ; 16(21): 27075-27086, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38752796

RESUMO

Multifaceted nanoplatforms integrating fluorescence imaging and chemotherapy have garnered acknowledgment for their potential potency in cancer diagnosis and simultaneous in situ therapy. However, some drawbacks remain for traditional organic photosensitizers, such as poor photostability, short excitation wavelength, and shallow penetration depth, which will greatly lower the chemotherapy treatment efficiency. Herein, we present lipid-encapsulated two-photon active aggregation-induced emission (AIE) luminogen and paclitaxel (PTX) nanoparticles (AIE@PTX NPs) with bright red fluorescence emission, excellent photostability, and good biocompatibility. The AIE@PTX NPs exhibit dual functionality as two-photon probes for visualizing blood vessels and tumor structures, achieving penetration depth up to 186 and 120 µm, respectively. Furthermore, the tumor growth of the HeLa-xenograft model can be effectively prohibited after the fluorescence imaging-guided and PTX-induced chemotherapy, which shows great potential in the clinical application of two-photon cell and tumor fluorescence imaging and cancer treatment.


Assuntos
Nanopartículas , Paclitaxel , Fótons , Nanomedicina Teranóstica , Paclitaxel/química , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Animais , Células HeLa , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/diagnóstico por imagem , Imagem Óptica , Camundongos Nus , Camundongos Endogâmicos BALB C , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia
9.
Int J Mol Sci ; 25(10)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38791209

RESUMO

Nanoparticles (NPs) are extremely important tools to overcome the limitations imposed by therapeutic agents and effectively overcome biological barriers. Smart designed/tuned nanostructures can be extremely effective for cancer treatment. The selection and design of nanostructures and the adjustment of size and surface properties are extremely important, especially for some precision treatments and drug delivery (DD). By designing specific methods, an important era can be opened in the biomedical field for personalized and precise treatment. Here, we focus on advances in the selection and design of nanostructures, as well as on how the structure and shape, size, charge, and surface properties of nanostructures in biological fluids (BFs) can be affected. We discussed the applications of specialized nanostructures in the therapy of head and neck cancer (HNC), which is a difficult and aggressive type of cancer to treat, to give an impetus for novel treatment approaches in this field. We also comprehensively touched on the shortcomings, current trends, and future perspectives when using nanostructures in the treatment of cancer.


Assuntos
Nanoestruturas , Humanos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Nanopartículas/química , Nanopartículas/uso terapêutico , Animais
10.
Artif Cells Nanomed Biotechnol ; 52(1): 321-333, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38795050

RESUMO

Polydopamine (PDA) stands as a versatile material explored in cancer nanomedicine for its unique properties, offering opportunities for multifunctional drug delivery platforms. This study explores the potential of utilizing a one-pot synthesis to concurrently integrate Fe, Gd and Mn ions into porous PDA-based theranostic drug delivery platforms called Ferritis, Gadolinis and Manganis, respectively. Our investigation spans the morphology, magnetic properties, photothermal characteristics and cytotoxicity profiles of those potent nanoformulations. The obtained structures showcase a spherical morphology, robust magnetic response and promising photothermal behaviour. All of the presented nanoparticles (NPs) display pronounced paramagnetism, revealing contrasting potential for MRI imaging. Relaxivity values, a key determinant of contrast efficacy, demonstrated competitive or superior performance compared to established, used contrasting agents. These nanoformulations also exhibited robust photothermal properties under near infra-red irradiation, showcasing their possible application for photothermal therapy of cancer. Our findings provide insights into the potential of metal-doped PDA NPs for cancer theranostics.


Assuntos
Indóis , Imageamento por Ressonância Magnética , Polímeros , Indóis/química , Humanos , Polímeros/química , Meios de Contraste/química , Nanopartículas/química , Nanopartículas/uso terapêutico , Manganês/química , Nanomedicina Teranóstica/métodos
11.
Mikrochim Acta ; 191(6): 326, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740583

RESUMO

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.


Assuntos
Movimento Celular , Quimioterapia Combinada , Nanopartículas , Neoplasias , Dióxido de Silício , Movimento Celular/efeitos dos fármacos , Dióxido de Silício/química , Quimioterapia Combinada/métodos , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas/química , Sistemas de Liberação de Fármacos por Nanopartículas/uso terapêutico , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanopartículas/ultraestrutura , Células A549 , Microscopia Eletrônica de Transmissão , Humanos
12.
Cell Rep Methods ; 4(5): 100782, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38772343

RESUMO

In a recent issue of Nature Nanotechnology, Zeng et al. report that arraying immuno-stimulatory CpG molecules with specific nanoscale spacing on DNA origami nanoparticles enhanced Th1-polarized immune responses. These results highlight spatial presentation of adjuvants as a design strategy to optimize cancer vaccine efficacy, safety, and tolerability.


Assuntos
Imunoterapia , Neoplasias , Imunoterapia/métodos , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Ligantes , Receptores Toll-Like/agonistas , Receptores Toll-Like/imunologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Animais , Vacinas Anticâncer/imunologia , Adjuvantes Imunológicos/farmacologia
13.
J Wound Care ; 33(Sup4a): xcix-cx, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38588056

RESUMO

Metal-based nanoparticles (MNPs) are promoted as effective compounds in the treatment of bacterial infections and as possible alternatives to antibiotics. These MNPs are known to affect a broad spectrum of microorganisms using a multitude of strategies, including the induction of reactive oxygen species and interaction with the inner structures of the bacterial cells. The aim of this review was to summarise the latest studies about the effect of metal-based nanoparticles on pathogenic bacterial biofilm formed in wounds, using the examples of Gram-positive bacterium Staphylococcus aureus and Gram-negative bacterium Pseudomonas aeruginosa, as well as provide an overview of possible clinical applications.


Assuntos
Nanopartículas , Infecções Estafilocócicas , Infecção dos Ferimentos , Humanos , Biofilmes , Staphylococcus aureus , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Pseudomonas aeruginosa , Nanopartículas/uso terapêutico , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia
14.
J Hematol Oncol ; 17(1): 16, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566199

RESUMO

Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation. Nanoparticles, engineered to reshape the TME, have shown promising results in enhancing immunotherapy by facilitating targeted delivery and immune modulation. These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, and encourage T cell infiltration. Biomimetic nanoparticles further enhance immunotherapy by increasing the internalization of immunomodulatory agents in immune cells such as dendritic cells. Moreover, exosomes, whether naturally secreted by cells in the body or bioengineered, have been explored to regulate the TME and immune-related cells to affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated by pH, redox, and light conditions, exhibit the potential to accelerate immunotherapy. The co-application of nanoparticles with immune checkpoint inhibitors is an emerging strategy to boost anti-tumor immunity. With their ability to induce long-term immunity, nanoarchitectures are promising structures in vaccine development. This review underscores the critical role of nanoparticles in overcoming current challenges and driving the advancement of cancer immunotherapy and TME modification.


Assuntos
Nanopartículas , Neoplasias , Humanos , Microambiente Tumoral , Imunoterapia , Diferenciação Celular , Nanopartículas/uso terapêutico , Neoplasias/terapia
15.
ACS Appl Mater Interfaces ; 16(15): 18252-18267, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38581365

RESUMO

Nitric oxide (NO) intervenes, that is, a potential treatment strategy, and has attracted wide attention in the field of tumor therapy. However, the therapeutic effect of NO is still poor, due to its short half-life and instability. Therapeutic concentration ranges of NO should be delivered to the target tissue sites, cell, and even subcellular organelles and to control NO generation. Mitochondria have been considered a major target in cancer therapy for their essential roles in cancer cell metabolism and apoptosis. In this study, mesoporous silicon-coated gold nanorods encapsulated with a mitochondria targeted and the thermosensitive lipid layer (AuNR@MSN-lipid-DOX) served as the carrier to load NO prodrug (BNN6) to build the near-infrared-triggered synergetic photothermal NO-chemotherapy platform (AuNR@MSN(BNN6)-lipid-DOX). The core of AuNR@MSN exhibited excellent photothermal conversion capability and high loading efficiency in terms of BNN6, reaching a high value of 220 mg/g (w/w), which achieved near-infrared-triggered precise release of NO. The outer biocompatible lipid layer, comprising thermosensitive phospholipid DPPC and mitochondrial-targeted DSPE-PEG2000-DOX, guided the whole nanoparticle to the mitochondria of 4T1 cells observed through confocal microscopy. In the mitochondria, the nanoparticles increased the local temperature over 42 °C under NIR irradiation, and a high NO concentration from BNN6 detected by the NO probe and DSPE-PEG2000-DOX significantly inhibited 4T1 cancer cells in vitro and in vivo under the synergetic photothermal therapy (PTT)-NO therapy-chemotherapy modes. The built NIR-triggered combination therapy nanoplatform can serve as a strategy for multimodal collaboration.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas , Fosfatidiletanolaminas , Polietilenoglicóis , Doxorrubicina/farmacologia , Óxido Nítrico , Fototerapia , Nanopartículas/uso terapêutico , Mitocôndrias , Lipídeos , Linhagem Celular Tumoral
16.
J Nanobiotechnology ; 22(1): 144, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566094

RESUMO

Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this study, phenytoin (PHT) loaded layered double hydroxide nanoparticles (BSA-LDHs-PHT) were fabricated via a coprecipitation - hydrothermal method for epileptic seizure control. In this study, we expound on the preparation method and characterization of BSA-LDHs-PHT. In-vitro drug release experiment shows both rapid and continuous drug release from BSA-LDHs-PHT, which is crucial for acute seizure control and chronic epilepsy therapy. In-vivo biodistribution assays after intranasal administration indicate excellent brain targeting ability of BSA-LDHs. Compared to BSA-Cyanine5.5, BSA-LDHs-Cyanine5.5 were associated with a higher brain/peripheral ratio across all tested time points. Following intranasal delivery with small doses of BSA-LDHs-PHT, the latency of seizures in the pentylenetetrazole-induced mouse models was effectively improved. Collectively, the present study successfully designed and applied BSA-LDHs-PHT as a promising strategy for treating epileptic seizures with an enhanced therapeutic effect.


Assuntos
Epilepsia , Nanopartículas , Camundongos , Animais , Fenitoína/farmacologia , Fenitoína/uso terapêutico , Administração Intranasal , Distribuição Tecidual , Convulsões/tratamento farmacológico , Epilepsia/tratamento farmacológico , Nanopartículas/uso terapêutico , Hidróxidos/uso terapêutico
17.
Nanoscale ; 16(17): 8236-8255, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38584466

RESUMO

Osteoporosis, characterized by a reduction in bone mineral density, represents a prevalent skeletal disorder with substantial global health implications. Conventional therapeutic strategies, exemplified by bisphosphonates and hormone replacement regimens, though effective, encounter inherent limitations and challenges. Recent years have witnessed the surge of cell-membrane-coated nanoparticles (CMNPs) as a promising intervention for osteoporosis, leveraging their distinct attributes including refined biocompatibility, heightened pharmaceutical payload capacity, as well as targeted drug release kinetics. However, a comprehensive review consolidating the application of CMNPs-based therapy for osteoporosis remains absent within the existing literature. In this review, we provide a concise overview of the distinctive pathogenesis associated with osteoporosis, alongside an in-depth exploration of the physicochemical attributes intrinsic to CMNPs derived from varied cellular sources. Subsequently, we explore the potential utility of CMNPs, elucidating emerging trends in their deployment for osteoporosis treatment through multifaceted therapeutic approaches. By linking the notable attributes of CMNPs with their roles in mitigating osteoporosis, this review serves as a catalyst for further advances in the design of advanced CMNPs tailored for osteoporosis management. Ultimately, such progress is promising for enhancing outcomes in anti-bone loss interventions, paving the way for clinical translation in the near future.


Assuntos
Membrana Celular , Nanopartículas , Osteoporose , Humanos , Osteoporose/tratamento farmacológico , Nanopartículas/química , Nanopartículas/uso terapêutico , Membrana Celular/metabolismo , Membrana Celular/química , Sistemas de Liberação de Medicamentos , Animais
18.
Acta Biomater ; 180: 394-406, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38615810

RESUMO

The construction and optimization of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) functions remain challenging. In this study, we aimed to design and synthesize four donor-acceptor (D-A) type aggregation-induced emission molecules: PSI, TPSI, PSSI, and TPSSI. We employed phenothiazine as an electron donor and 1,3-bis(dicyanomethylidene)indan as a strong electron acceptor in the synthesis process. Among them, TPSSI exhibited efficient type I reactive oxygen species generation, high photothermal conversion efficiency (45.44 %), and near-infrared emission. These observations can be attributed to the introduction of a triphenylamine electron donor group and a thiophene unit, which resulted in increased D-A strengths, a reduced singlet-triplet energy gap, and increased free intramolecular motion. TPSSI was loaded into bovine serum albumin to prepare biocompatible TPSSI nanoparticles (NPs). Our results have indicated that TPSSI NPs can target lipid droplets with negligible dark toxicity and can efficiently generate O2•- in hypoxic tumor environments. Moreover, TPSSI NPs selectively targeted 4T1 tumor tissues and exhibited a good PDT-PTT synergistic effect in vitro and in vivo. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technologies. STATEMENT OF SIGNIFICANCE: The construction of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy, and photothermal therapy functions, and its optimization remain challenging. In this study, we construct four donor-acceptor aggregation-induced emission molecules using phenothiazine as an electron donor and 1,3-Bis(dicyanomethylidene)indan as a strong electron acceptor. By optimizing the molecular structure, an integrated phototherapy agent with fluorescence imaging ability and high photodynamic / photothermal therapy performance was prepared. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technology.


Assuntos
Fotoquimioterapia , Terapia Fototérmica , Animais , Fotoquimioterapia/métodos , Camundongos , Feminino , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Raios Infravermelhos , Nanopartículas/química , Nanopartículas/uso terapêutico
19.
Biomater Adv ; 160: 213859, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38642515

RESUMO

Triple-negative breast cancer (TNBC) is a highly invasive and metastatic subtype of breast cancer that often recurs after surgery. Herein, we developed a cyclodextrin-based tumor-targeted nano delivery system that incorporated the photosensitizer chlorin e6 (Ce6) and the chemotherapeutic agent lonidamine (LND) to form the R6RGD-CMßCD-se-se-Ce6/LND nanoparticles (RCC/LND NPS). This nanosystem could target cancer cells, avoid lysosomal degradation and further localize within the mitochondria. The RCC/LND NPS had pH and redox-responsive to control the release of Ce6 and LND. Consequently, the nanosystem had a synergistic effect by effectively alleviating hypoxia, enhancing the production of cytotoxic reactive oxygen species (ROS) and amplifying the efficacy of photodynamic therapy (PDT). Furthermore, the RCC/LND NPS + light weakened anoikis resistance, disrupted extracellular matrix (ECM), activated both the intrinsic apoptotic pathway (mitochondrial pathway) and extrinsic apoptotic pathway (receptor death pathway) of anoikis. In addition, the nanosystem showed significant anti-TNBC efficacy in vivo. These findings collectively demonstrated that RCC/LND NPS + light enhanced the anticancer effects, induced anoikis and inhibited tumor cell migration and invasion through a synergistic effect of chemotherapy and PDT. Overall, this study highlighted the promising potential of the RCC/LND NPS + light for the treatment of TNBC.


Assuntos
Anoikis , Apoptose , Clorofilídeos , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Humanos , Fotoquimioterapia/métodos , Feminino , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Animais , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Anoikis/efeitos dos fármacos , Nanopartículas/química , Nanopartículas/uso terapêutico , Apoptose/efeitos dos fármacos , Indazóis/farmacologia , Indazóis/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Camundongos
20.
ACS Appl Mater Interfaces ; 16(17): 21400-21414, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38640094

RESUMO

Morin, a naturally occurring bioactive compound shows great potential as an antioxidant, anti-inflammatory agent, and regulator of blood glucose levels. However, its low water solubility, poor lipid solubility, limited bioavailability, and rapid clearance in vivo hinder its application in blood glucose regulation. To address these limitations, we report an enzymatically synthesized nanosized morin particle (MNs) encapsulated in sodium alginate microgels (M@SA). This approach significantly enhances morin's delivery efficiency and therapeutic efficacy in blood glucose regulation. Utilizing horseradish peroxidase, we synthesized MNs averaging 305.7 ± 88.7 nm in size. These MNs were then encapsulated via electrohydrodynamic microdroplet spraying to form M@SA microgels. In vivo studies revealed that M@SA microgels demonstrated prolonged intestinal retention and superior efficacy compared with unmodified morin and MNs alone. Moreover, MNs notably improved glucose uptake in HepG2 cells. Furthermore, M@SA microgels effectively regulated blood glucose, lipid profiles, and oxidative stress in diabetic mice while mitigating liver, kidney, and pancreatic damage and enhancing anti-inflammatory responses. Our findings propose a promising strategy for the oral administration of natural compounds for blood glucose regulation, with implications for broader therapeutic applications.


Assuntos
Glicemia , Diabetes Mellitus Experimental , Flavonas , Flavonoides , Nanopartículas , Animais , Humanos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Camundongos , Flavonoides/química , Flavonoides/farmacologia , Células Hep G2 , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/sangue , Nanopartículas/química , Nanopartículas/uso terapêutico , Alginatos/química , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/química , Antioxidantes/farmacologia , Masculino , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia
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