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1.
Int J Pharm ; 654: 123999, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38490403

RESUMO

Colorectal cancer (CC) is one of the most predominant malignancies in the world, with the current treatment regimen consisting of surgery, radiation therapy, and chemotherapy. Chemotherapeutic drugs, such as 5-fluorouracil (5-FU), have gained popularity as first-line antineoplastic agents against CC but have several drawbacks, including variable absorption through the gastrointestinal tract, inconsistent liver metabolism, short half-life, toxicological reactions in several organ systems, and others. Therefore, herein, we develop chitosan-coated zinc-substituted cobalt ferrite nanoparticles (CZCFNPs) for the pH-sensitive (triggered by chitosan degradation within acidic organelles of cells) and sustained delivery of 5-FU in CC cells in vitro. Additionally, the developed nanoplatform served as an excellent exogenous optical coherence tomography (OCT) contrast agent, enabling a significant improvement in the OCT image contrast in a CC tissue phantom model with a biomimetic microvasculature. Further, this study opens up new possibilities for using OCT for the non-invasive monitoring and/or optimization of magnetic targeting capabilities, as well as real-time tracking of magnetic nanoparticle-based therapeutic platforms for biomedical applications. Overall, the current study demonstrates the development of a CZCFNP-based theranostic platform capable of serving as a reliable drug delivery system as well as a superior OCT exogenous contrast agent for tissue imaging.


Assuntos
Quitosana , Cobalto , Compostos Férricos , Nanopartículas , Medicina de Precisão , Meios de Contraste , Zinco , Tomografia de Coerência Óptica , Sistemas de Liberação de Medicamentos , Fluoruracila/uso terapêutico , Concentração de Íons de Hidrogênio , Nanomedicina Teranóstica
2.
ACS Appl Mater Interfaces ; 16(10): 12332-12338, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38426453

RESUMO

Organic dye-based agents with near-infrared (NIR)-II absorption have great potential for cancer theranostics because of the deeper tissue penetration and good biocompatibility. However, proper design is required to develop NIR-II-absorbing dyes with good optical properties. We proposed to construct chalcogen atom-modulated croconaine for NIR-II light-triggered photothermal theranostics. By introducing different chalcogen atoms (O, S, Se, or Te) into the structure of croconaine, the light absorption of croconaine can be precisely regulated from the NIR-I to the NIR-II range due to the heavy-atom effect. Especially, Te-substituted croconaine (CRTe) and its nanoformulations exhibit superior NIR-II responsiveness, a high photothermal conversion efficiency (70.6%), and good photostability. With their favorable tumor accumulation, CRTe-NPs from tumor regions can be visualized by NIR-II optoacoustic systems with high resolution and high contrast; meanwhile, their superior photothermal performance also contributes to efficient cell killing and tumor elimination upon 1064 nm laser irradiation. Therefore, this work provides an efficient strategy for the molecular design of NIR-II organic photothermal agents.


Assuntos
Calcogênios , Nanopartículas , Neoplasias , Humanos , Nanomedicina Teranóstica , Neoplasias/tratamento farmacológico , Corantes/química , Calcogênios/farmacologia , Nanopartículas/química , Fototerapia , Linhagem Celular Tumoral
3.
J Control Release ; 368: 650-662, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38490374

RESUMO

Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an "extended conjugation & molecular rotor" strategy for multimodal imaging and phototherapy of deep orthotopic GBM. IRLy was synthesized successfully through a rational molecular rotor modification with stronger penetration, higher signal-to-noise ratio, and a high photothermal conversion efficiency (PCE) up to ∼60%, which can achieve efficient NIR-II photo-response. The multifunctional nanoparticles (Tf-IRLy NPs) were further fabricated to cross the blood-brain barrier (BBB) introducing transferrin (Tf) as a targeting ligand. Tf-IRLy NPs showed high biosafety and good tumor enrichment for GBM in vitro and in vivo, and thus enabled accurate, efficient, and less invasive NIR-II multimodal imaging and photothermal therapy. This versatile Tf-IRLy nanosystem can provide a reference for the efficient, precise and low-invasive multi-synergistic brain targeted photo-theranostics. In addition, the "extended conjugation & molecular rotor" strategy can be used to guide the design of other photothermal agents.


Assuntos
Glioblastoma , Nanopartículas , Neoplasias , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/terapia , Fototerapia/métodos , Encéfalo , Barreira Hematoencefálica , Corantes , Nanomedicina Teranóstica/métodos , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral
4.
Anal Chem ; 96(13): 5315-5322, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38511619

RESUMO

Photoacoustic imaging (PAI) in the second near-infrared region (NIR-II), due to deeper tissue penetration and a lower background interference, has attracted widespread concern. However, the development of NIR-II nanoprobes with a large molar extinction coefficient and a high photothermal conversion efficiency (PCE) for PAI and photothermal therapy (PTT) is still a big challenge. In this work, the NIR-II CuTe nanorods (NRs) with large molar extinction coefficients ((1.31 ± 0.01) × 108 cm-1·M-1 at 808 nm, (7.00 ± 0.38) × 107 cm-1·M-1 at 1064 nm) and high PCEs (70% at 808 nm, 48% at 1064 nm) were synthesized by living Staphylococcus aureus (S. aureus) cells as biosynthesis factories. Due to the strong light-absorbing and high photothermal conversion ability, the in vitro PA signals of CuTe NRs were about 6 times that of indocyanine green (ICG) in both NIR-I and NIR-II. In addition, CuTe NRs could effectively inhibit tumor growth through PTT. This work provides a new strategy for developing NIR-II probes with large molar extinction coefficients and high PCEs for NIR-II PAI and PTT.


Assuntos
Nanopartículas , Nanotubos , Técnicas Fotoacústicas , Fototerapia/métodos , Técnicas Fotoacústicas/métodos , Staphylococcus aureus , Nanomedicina Teranóstica/métodos
5.
ACS Biomater Sci Eng ; 10(4): 2510-2522, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38466622

RESUMO

Theranostic systems, which integrate therapy and diagnosis into a single platform, have gained significant attention as a promising approach for noninvasive cancer treatment. The field of image-guided therapy has revolutionized real-time tumor detection, and within this domain, plasmonic nanostructures have garnered significant attention. These structures possess unique localized surface plasmon resonance (LSPR), allowing for enhanced absorption in the near-infrared (NIR) range. By leveraging the heat generated from plasmonic nanoparticles upon NIR irradiation, target cancer cells can be effectively eradicated. This study introduces a plasmonic gold dogbone-nanorattle (AuDB NRT) structure that exhibits broad absorption in the NIR region and demonstrates a photothermal conversion efficiency of 35.29%. When exposed to an NIR laser, the AuDB NRTs generate heat, achieving a maximum temperature rise of 38 °C at a concentration of 200 µg/mL and a laser power density of 3 W/cm2. Additionally, the AuDB NRTs possess intrinsic electromagnetic hotspots that amplify the signal of a Raman reporter molecule, making them an excellent probe for surface-enhanced Raman scattering-based bioimaging of cancer cells. To improve the biocompatibility of the nanorattles, the AuDB NRTs were conjugated with mPEG-thiol and successfully encapsulated into cationic dextrin nanoparticles (CD NPs). Biocompatibility tests were performed on HEK 293 A and MCF-7 cell lines, revealing high cell viability when exposed to AuDB NRT-CD NPs. Remarkably, even at a low laser power density of 1 W/cm2, the application of the NIR laser resulted in a remarkable 80% cell death in cells treated with a nanocomposite concentration of 100 µg/mL. Further investigation elucidated that the cell death induced by photothermal heat followed an apoptotic mechanism. Overall, our findings highlight the significant potential of the prepared nanocomposite for cancer theranostics, combining effective photothermal therapy along with the ability to image cancer cells.


Assuntos
Nanocompostos , Nanopartículas , Neoplasias , Humanos , Ouro/farmacologia , Ouro/química , Dextrinas , Nanomedicina Teranóstica/métodos , Células HEK293 , Nanopartículas/uso terapêutico , Neoplasias/terapia
6.
Molecules ; 29(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38474496

RESUMO

Chemiluminescence (CL) is of great significance in biochemical analysis and imaging due to its high sensitivity and lack of need for external excitation. In this review, we summarized the recent progress of AIE-based CL systems, including their working mechanisms and applications in biochemical analysis, bioimaging, and disease diagnosis and treatment. In ion and molecular detection, CL shows high selectivity and high sensitivity, especially in the detection of dynamic reactive oxygen species (ROS). Further, the integrated NIR-CL single-molecule system and nanostructural CL platform harnessing CL resonance energy transfer (CRET) have remarkable advantages in long-term imaging with superior capability in penetrating deep tissue depth and high signal-to-noise ratio, and are promising in the applications of in vivo imaging and image-guided disease therapy. Finally, we summarized the shortcomings of the existing AIE-CL system and provided our perspective on the possible ways to develop more powerful CL systems in the future. It can be highly expected that these promoted CL systems will play bigger roles in biochemical analysis and disease theranostics.


Assuntos
Luminescência , Nanoestruturas , Medicina de Precisão , Diagnóstico por Imagem , Nanomedicina Teranóstica/métodos
7.
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
8.
Nanoscale ; 16(13): 6330-6364, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38470224

RESUMO

Recent years have witnessed dramatic improvements in nanotechnology-based cancer therapeutics, and it continues to evolve from the use of conventional therapies (chemotherapy, surgery, and radiotherapy) to increasingly multi-complex approaches incorporating thermal energy-based tumor ablation (e.g. magnetic hyperthermia and photothermal therapy), dynamic therapy (e.g. photodynamic therapy), gene therapy, sonodynamic therapy (e.g. ultrasound), immunotherapy, and more recently real-time treatment efficacy monitoring (e.g. theranostic MRI-sensitive nanoparticles). Unlike monotherapy, these multimodal therapies (bimodal, i.e., a combination of two therapies, and trimodal, i.e., a combination of more than two therapies) incorporating nanoplatforms have tremendous potential to improve the tumor tissue penetration and retention of therapeutic agents through selective active/passive targeting effects. These combinatorial therapies can correspondingly alleviate drug response against hypoxic/acidic and immunosuppressive tumor microenvironments and promote/induce tumor cell death through various multi-mechanisms such as apoptosis, autophagy, and reactive oxygen-based cytotoxicity, e.g., ferroptosis, etc. These multi-faced approaches such as targeting the tumor vasculature, neoangiogenic vessels, drug-resistant cancer stem cells (CSCs), preventing intra/extravasation to reduce metastatic growth, and modulation of antitumor immune responses work complementary to each other, enhancing treatment efficacy. In this review, we discuss recent advances in different nanotechnology-mediated synergistic/additive combination therapies, emphasizing their underlying mechanisms for improving cancer prognosis and survival outcomes. Additionally, significant challenges such as CSCs, hypoxia, immunosuppression, and distant/local metastasis associated with therapy resistance and tumor recurrences are reviewed. Furthermore, to improve the clinical precision of these multimodal nanoplatforms in cancer treatment, their successful bench-to-clinic translation with controlled and localized drug-release kinetics, maximizing the therapeutic window while addressing safety and regulatory concerns are discussed. As we advance further, exploiting these strategies in clinically more relevant models such as patient-derived xenografts and 3D organoids will pave the way for the application of precision therapy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Nanomedicina , Neoplasias/tratamento farmacológico , Nanotecnologia , Sistemas de Liberação de Medicamentos , Nanopartículas/uso terapêutico , Nanomedicina Teranóstica , Microambiente Tumoral
9.
ACS Appl Mater Interfaces ; 16(8): 9816-9825, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38381128

RESUMO

Imaging-guided photodynamic therapy (PDT) holds great potential for tumor therapy. However, achieving the synergistic enhancement of the reactive oxygen species (ROS) generation efficiency and fluorescence emission of photosensitizers (PSs) remains a challenge, resulting in suboptimal image guidance and theranostic efficacy. The hypoxic tumor microenvironment also hinders the efficacy of PDT. Herein, we propose a "two-stage rocket-propelled" photosensitive system for tumor cell ablation. This system utilizes MitoS, a mitochondria-targeted PS, to ablate tumor cells. Importantly, MitoS can react with HClO to generate a more efficient PS, MitoSO, with a significantly improved fluorescence quantum yield. Both MitoS and MitoSO exhibit less O2-dependent type I ROS generation capability, inducing apoptosis and ferroptosis. In vivo PDT results confirm that this mitochondrial-specific type I-II cascade phototherapeutic strategy is a potent intervention for tumor downstaging. This study not only sheds light on the correlation between the PS structure and the ROS generation pathway but also proposes a novel and effective strategy for tumor downstaging intervention.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Medicina de Precisão , Espécies Reativas de Oxigênio/metabolismo , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Mitocôndrias/metabolismo , Linhagem Celular Tumoral , Nanomedicina Teranóstica/métodos , Microambiente Tumoral
10.
Nanomedicine ; 57: 102738, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38341011

RESUMO

Tumor recurrence, which happens as a result of persisting tumor cells and minor lesions after treatments like surgery and chemotherapy, is a major problem in oncology. Herein, a strategy to combat this issue by utilize a theranostic nanovaccine composed of photonic HCuS. This nanovaccine aims to eradicate cancer cells and their traces while also preventing tumor recurrence via optimizing the photothermal immune impact. Successful membrane targeting allows for the introduction of new therapeutic agents into the tumor cells. Together with co-encapsulated Toll-Like Receptors (TLR7/8) agonist R848 for activating T cells and maturing DCs, the combined effects of HCuS and ICG function as photothermal agents that generate heat in the presence of NIR light. Photothermal-mediated immunotherapy with therapeutic modalities proved successful in killing tumor cells. By activating the immune system, this new photonic nanovaccine greatly increases immunogenic cell death (ICD), kills tumor cells, and prevents their recurrence.


Assuntos
Nanopartículas , Fototerapia , Humanos , Nanomedicina Teranóstica , Microambiente Tumoral , Recidiva Local de Neoplasia , Linhagem Celular Tumoral , Imunoterapia , Nanopartículas/uso terapêutico
11.
Chem Rev ; 124(5): 2699-2804, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38422393

RESUMO

The ability to gain spatiotemporal information, and in some cases achieve spatiotemporal control, in the context of drug delivery makes theranostic fluorescent probes an attractive and intensely investigated research topic. This interest is reflected in the steep rise in publications on the topic that have appeared over the past decade. Theranostic fluorescent probes, in their various incarnations, generally comprise a fluorophore linked to a masked drug, in which the drug is released as the result of certain stimuli, with both intrinsic and extrinsic stimuli being reported. This release is then signaled by the emergence of a fluorescent signal. Importantly, the use of appropriate fluorophores has enabled not only this emerging fluorescence as a spatiotemporal marker for drug delivery but also has provided modalities useful in photodynamic, photothermal, and sonodynamic therapeutic applications. In this review we highlight recent work on theranostic fluorescent probes with a particular focus on probes that are activated in tumor microenvironments. We also summarize efforts to develop probes for other applications, such as neurodegenerative diseases and antibacterials. This review celebrates the diversity of designs reported to date, from discrete small-molecule systems to nanomaterials. Our aim is to provide insights into the potential clinical impact of this still-emerging research direction.


Assuntos
Corantes Fluorescentes , Medicina de Precisão , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Fluorescência , Nanomedicina Teranóstica
12.
Angew Chem Int Ed Engl ; 63(14): e202318609, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38345594

RESUMO

The fabrication of a multimodal phototheranostic platform on the basis of single-component theranostic agent to afford both imaging and therapy simultaneously, is attractive yet full of challenges. The emergence of aggregation-induced emission luminogens (AIEgens), particularly those emit fluorescence in the second near-infrared window (NIR-II), provides a powerful tool for cancer treatment by virtue of adjustable pathway for radiative/non-radiative energy consumption, deeper penetration depth and aggregation-enhanced theranostic performance. Although bulky thiophene π-bridges such as ortho-alkylated thiophene, 3,4-ethoxylene dioxythiophene and benzo[c]thiophene are commonly adopted to construct NIR-II AIEgens, the subtle differentiation on their theranostic behaviours has yet to be comprehensively investigated. In this work, systematical investigations discovered that AIEgen BT-NS bearing benzo[c]thiophene possesses acceptable NIR-II fluorescence emission intensity, efficient reactive oxygen species generation, and high photothermal conversion efficiency. Eventually, by using of BT-NS nanoparticles, unprecedented performance on NIR-II fluorescence/photoacoustic/photothermal imaging-guided synergistic photodynamic/photothermal elimination of tumors was demonstrated. This study thus offers useful insights into developing versatile phototheranostic systems for clinical trials.


Assuntos
Nanopartículas , Neoplasias , Humanos , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Nanopartículas/uso terapêutico , Medicina de Precisão , Linhagem Celular Tumoral
13.
Cancer Treat Rev ; 124: 102698, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38359590

RESUMO

In the last years, theranostics has expanded the therapeutic options available for prostate cancer patients. In this review, we explore this dynamic field and its potential to revolutionize precision medicine for prostate cancer. We delve into the foundational principles, clinical applications, and emerging opportunities, emphasizing the potential synergy between radioligand therapy and other systemic treatments. Additionally, we address the ongoing challenges, including optimizing patient selection, assessing treatment responses, and determining the role of theranostics within the broader landscape of prostate cancer treatment.


Assuntos
Medicina de Precisão , Neoplasias da Próstata , Masculino , Humanos , Nanomedicina Teranóstica , Neoplasias da Próstata/terapia
14.
Int J Biol Macromol ; 262(Pt 2): 130209, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38365155

RESUMO

This study presents the development of organo-bentonites (OBs); a cost-effective drug delivery system holding both sensing and imaging capabilities. The OBs were synthesized using quaternary ammonium cations derived from chitosan, Lawsonia inermis, and pyrene/anthracene carboxaldehyde combinations through a three-step process: Mannich reaction, quaternization, and intercalation. Physicochemical characterization confirms the organic modification of bentonite. The OBs: NQPB and NQAB hold substantial ciprofloxacin (Cipro) loading capacities (71.51 % and 78.04 %, respectively) and exhibit pH-dependent release profiles, suggesting their potential use as drug delivery platforms. Cell viability evaluation by MTT and live-dead assays indicates favourable results. Both OBs demonstrate fluorescence within the 450-500 nm range, and they display concentration-dependent fluorescence quenching and enhancement for NQPB and NQAB, respectively, in the presence of tryptophan (Trp), making them suitable for its detection. Confocal analysis further enunciates the live intracellular fluorescence upon OB uptake. In summary, the intrinsically fluorescent mesoporous OBs synthesized from Lawsonia inermis and chitosan exhibit multifunctionality, including Cipro delivery, Trp sensing, and live cell imaging. Among the OBs, NQAB could be considered as a promising theranostic platform owing to its superior cytocompatibility (>80 %), appreciable fluorescence, and controlled release profile.


Assuntos
Quitosana , Lawsonia (Planta) , Bentonita/química , Lawsonia (Planta)/química , Argila , Nanomedicina Teranóstica , Sistemas de Liberação de Medicamentos , Ciprofloxacina/farmacologia
15.
Eur J Med Chem ; 267: 116173, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38320425

RESUMO

Near-infrared two-region (NIR-II, 1000-1700 nm) fluorescence imaging has received widespread attention because of its high in vivo penetration depth, high imaging resolution, fast imaging speed and high efficiency, dynamic imaging, and high clinical translatability. This paper reviews the application of NIR-II imaging technology in disease diagnosis and treatment. The paper highlights the latest research progress of commonly used NIR-II imaging materials and the latest progress of multifunctional diagnostic platforms based on NIR-II imaging technology, and discusses the challenges and directions for the development and utilization of novel NIR-II imaging probes.


Assuntos
Imagem Óptica , Nanomedicina Teranóstica , Nanomedicina Teranóstica/métodos , Imagem Óptica/métodos , Corantes Fluorescentes
16.
ACS Appl Mater Interfaces ; 16(6): 6859-6867, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38299497

RESUMO

The rapid development of nanomedicine has considerably advanced precision therapy for cancer treatment. Superior to traditional chemotherapy, emerging theranostic nanoprodrugs can effectively realize inherent self-tracking, targeted drug delivery, stimuli-triggered drug release, and reduced systemic toxicity of chemotherapeutic drugs. However, theranostic nanoprodrugs with real-time drug release monitoring have remained rare so far. In this work, we developed a new glutathione-responsive theranostic nanoprodrug with a high drug-loading content of 59.4 wt % and an average nanoscale size of 46 nm, consisting of the anticancer drug paclitaxel and a fluorescent imaging probe with a high fluorescence quantum yield, which are linked by a disulfide-based glutathione-sensitive self-immolating linker. The strong fluorescence emission of the fluorophore enables efficacious self-tracking and sensitive fluorescence "ON-OFF" glutathione sensing. Upon encountering high-level glutathione in cancer cells, the disulfide bond is cleaved, and the resulting linker halves spontaneously collapse into cyclic small molecules at the same pace, leading to the simultaneous release of the therapeutic drug and the fluorescence-OFF imaging probe. Thereby, the drug release process is efficiently monitored by the fluorescence change in the nanoprodrug. The nanoprodrugs exerted high cytotoxicity toward various cancer cells, especially for A549 and HEK-293 cells, in which the nanoprodrugs generated better therapeutic effects than free paclitaxel. Our work demonstrated a new modality of smart theranostic nanoprodrugs for precise cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Medicina de Precisão , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Elétrons , Células HEK293 , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Nanomedicina Teranóstica/métodos , Imagem Óptica/métodos , Glutationa/metabolismo , Dissulfetos/uso terapêutico , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
17.
Int J Nanomedicine ; 19: 1249-1272, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348177

RESUMO

Background: The anti-Programmed Death-Ligand 1 (termed aPD-L1) immune checkpoint blockade therapy has emerged as a promising treatment approach for various advanced solid tumors. However, the effect of aPD-L1 inhibitors limited by the tumor microenvironment makes most patients exhibit immunotherapy resistance. Methods: We conjugated the Sialyl Lewis X with a polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO-PEG) to form UPS nanoparticles (USPIO-PEG-SLex, termed UPS). The physicochemical properties of UPS were tested and characterized. Transmission electron microscopy and ICP-OES were used to observe the cellular uptake and targeting ability of UPS. Flow cytometry, mitochondrial membrane potential staining, live-dead staining and scratch assay were used to verify the in vitro photothermal effect of UPS, and the stimulation of UPS on immune-related pathways at the gene level was analyzed by sequencing. Biological safety analysis and pharmacokinetic analysis of UPS were performed. Finally, the amplification effect of UPS-mediated photothermal therapy on aPD-L1-mediated immunotherapy and the corresponding mechanism were studied. Results: In vitro experiments showed that UPS had strong photothermal therapy ability and was able to stimulate 5 immune-related pathways. In vivo, when the PTT assisted aPD-L1 treatment, it exhibited a significant increase in CD4+ T cell infiltration by 14.46-fold and CD8+ T cell infiltration by 14.79-fold, along with elevated secretion of tumor necrosis factor-alpha and interferon-gamma, comparing with alone aPD-L1. This PTT assisted aPD-L1 therapy achieved a significant inhibition of both primary tumors and distant tumors compared to the alone aPD-L1, demonstrating a significant difference. Conclusion: The nanotheranostic agent UPS has been introduced into immunotherapy, which has effectively broadened its application in biomedicine. This photothermal therapeutic approach of the UPS nanotheranostic agent enhancing the efficacy of aPD-L1 immune checkpoint blockade therapy, can be instructive to address the challenges associated with immunotherapy resistance, thereby offering potential for clinical translation.


Assuntos
Dextranos , Nanopartículas de Magnetita , Neoplasias , Humanos , Terapia Fototérmica , Antígeno Sialil Lewis X , Inibidores de Checkpoint Imunológico , Nanomedicina Teranóstica , Nanopartículas de Magnetita/uso terapêutico , Imunoterapia , Neoplasias/terapia , Microambiente Tumoral , Antígeno B7-H1 , Linhagem Celular Tumoral
18.
Adv Mater ; 36(14): e2309748, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38165653

RESUMO

One-for-all phototheranostics, referring to a single component simultaneously exhibiting multiple optical imaging and therapeutic modalities, has attracted significant attention due to its excellent performance in cancer treatment. Benefitting from the superiority in balancing the diverse competing energy dissipation pathways, aggregation-induced emission luminogens (AIEgens) are proven to be ideal templates for constructing one-for-all multimodal phototheranostic agents. However, to this knowledge, the all-round AIEgens that can be triggered by a second near-infrared (NIR-II, 1000-1700 nm) light have not been reported. Given the deep tissue penetration and high maximum permissible exposure of the NIR-II excitation light, herein, this work reports for the first time an NIR-II laser excitable AIE small molecule (named BETT-2) with multimodal phototheranostic features by taking full use of the advantage of AIEgens in single molecule-facilitated versatility as well as synchronously maximizing the molecular donor-acceptor strength and conformational distortion. As formulated into nanoparticles (NPs), the high performance of BETT-2 NPs in NIR-II light-driven fluorescence-photoacoustic-photothermal trimodal imaging-guided photodynamic-photothermal synergistic therapy of orthotopic mouse breast tumors is fully demonstrated by the systematic in vitro and in vivo evaluations. This work offers valuable insights for developing NIR-II laser activatable one-for-all phototheranostic systems.


Assuntos
Nanopartículas , Neoplasias , Animais , Camundongos , Luz , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Linhagem Celular Tumoral
19.
Adv Healthc Mater ; 13(9): e2303200, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38183410

RESUMO

Narrow photo-absorption range and low carrier utilization are significant barriers that restrict the antitumor efficiency of 2D bismuth oxyhalide (BiOX, X = Cl, Br, I) nanosheets (NSs). Introducing oxygen vacancy (OV) defects can expand the absorption range and improve carrier utilization, which are crucial but also challenging. In this study, a series of BiOxCl NSs with different OV defect concentrations (x = 1, 0.7, 0.5) is developed, which shows full spectrum absorption and strong absorption in the second near-infrared region (NIR-II). Density functional theory calculations are utilized to calculate the crystal structure and density states of BiOxCl, which confirm that part of the carriers is separated by OV enhanced internal electric field to improve carrier utilization. The carriers without redox reaction can be trapped in the OV, leading to great majority of photo-generated carriers promoting the photothermal performance. Triggered by single NIR-II (1064 nm), BiOxCl NSs' bidirectional efficient utilization of carriers achieves synchronously combined phototherapy, leading to enhanced tumor ablation and multimodal diagnostic in vitro and vivo. It is thus believed that this work provides an innovative strategy to design and construct nanoplatforms of indirect band gap semiconductors for clinical phototheranostics.


Assuntos
Nanopartículas , Neoplasias , Humanos , Oxigênio/química , Fototerapia/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Imagem Multimodal , Nanopartículas/química , Nanomedicina Teranóstica/métodos , Linhagem Celular Tumoral
20.
Chem Asian J ; 19(4): e202301036, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38230541

RESUMO

Malignant tumors seriously threaten human life and well-being. Emerging Near-infrared II (NIR-II, 1000-1700 nm) phototheranostic nanotechnology integrates diagnostic and treatment modalities, offering merits including improved tissue penetration and enhanced spatiotemporal resolution. This remarkable progress has opened promising avenues for advancing tumor theranostic research. The tumor microenvironment (TME) differs from normal tissues, exhibiting distinct attributes such as hypoxia, acidosis, overexpressed hydrogen peroxide, excess glutathione, and other factors. Capitalizing on these attributes, researchers have developed TME-activatable NIR-II phototheranostic agents with diagnostic and therapeutic attributes concurrently. Therefore, developing TME-activatable NIR-II phototheranostic agents with diagnostic and therapeutic activation holds significant research importance. Currently, research on TME-activatable NIR-II phototheranostic agents is still in its preliminary stages. This review examines the recent advances in developing dual-functional NIR-II activatable phototheranostic agents over the past years. It systematically presents NIR-II phototheranostic agents activated by various TME factors such as acidity (pH), hydrogen peroxide (H2 O2 ), glutathione (GSH), hydrogen sulfide (H2 S), enzymes, and their hybrid. This encompasses NIR-II fluorescence and photoacoustic imaging diagnostics, along with therapeutic modalities, including photothermal, photodynamic, chemodynamic, and gas therapies triggered by these TME factors. Lastly, the difficulties and opportunities confronting NIR-II activatable phototheranostic agents in the simultaneous diagnosis and treatment field are highlighted.


Assuntos
Nanopartículas , Neoplasias , Humanos , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Microambiente Tumoral , Peróxido de Hidrogênio , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Glutationa , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral
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