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1.
Angew Chem Int Ed Engl ; 63(18): e202401331, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38456641

RESUMO

A general approach to constructing room temperature phosphorescence (RTP) materials involves the incorporation of a phosphorescent emitter into a rigid host or polymers with high glass transition temperature. However, these materials often suffer from poor processability and suboptimal mechanical properties, limiting their practical applications. In this work, we developed benzothiadiazole-based dialkene (BTD-HEA), a multifunctional phosphorescent emitter with a remarkable yield of intersystem crossing (ΦISC, 99.83 %). Its high triplet exciton generation ability and dialkene structure enable BTD-HEA to act as a photoinitiator and crosslinker, efficiently initiating the polymerization of various monomers within 120 seconds. A range of flexible phosphorescence gels, including hydrogels, organogels, ionogels, and aerogels were fabricated, which exhibit outstanding stretchability and recoverability. Furthermore, the unique fluorescent-phosphorescent colorimetric properties of the gels provide a more sensitive method for the visual determination of the polymerization process. Notably, the phosphorescent emission intensity of the hydrogel can be increased by the formation of ice, allowing for the precise detection of hydrogel freezing. The versatility of this emitter paves the way for fabricating various flexible phosphorescence gels with diverse morphologies using microfluidics, film-shearing, roll coating process, and two/three-dimensional printing, showcasing its potential applications in the fields of bioimaging and bioengineering.

2.
J Am Chem Soc ; 146(14): 9888-9896, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38546165

RESUMO

Second near-infrared (NIR-II) optical imaging technology has emerged as a powerful tool for diagnostic and image-guided surgery due to its higher imaging contrast. However, a general strategy for efficiently designing NIR-II organic molecules is still lacking, because NIR-II dyes are usually difficult to synthesize, which has impeded the rapid development of NIR-II bioprobes. Herein, based on the theoretical calculations on 62 multiaryl-pyrrole (MAP) systems with spectra ranging from the visible to the NIR-II region, a continuous red shift of the spectra toward the NIR-II region could be achieved by adjusting the type and site of substituents on the MAPs. Two descriptors (ΔEgs and µgs) were identified as exhibiting strong correlations with the maximum absorption/emission wavelengths, and the descriptors could be used to predict the emission spectrum in the NIR-II region only if ΔEgs ≤ 2.5 eV and µgs ≤ 22.55 D. The experimental absorption and emission spectra of ten MAPs fully confirmed the theoretical predictions, and biological imaging in vivo of newly designed MAP23-BBT showed high spatial resolution in the NIR-II region in deep tissue angiography. More importantly, both descriptors of ΔEgs and µgs have shown general applicability to most of the reported donor-acceptor-donor-type non-MAP NIR-II dyes. These results have broad implications for the efficient design of NIR-II dyes.

3.
Chem Sci ; 15(12): 4222-4237, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38516079

RESUMO

Organic room-temperature phosphorescence (RTP) materials have attracted considerable attention for their extended afterglow at ambient conditions, eco-friendliness, and wide-ranging applications in bio-imaging, data storage, security inks, and emergency illumination. Significant advancements have been achieved in recent years in developing highly efficient RTP materials by manipulating the intermolecular interactions. In this perspective, we have summarized recent advances in ion-regulated organic RTP materials based on the roles and interactions of ions, including the ion-π interactions, electrostatic interactions, and coordinate interactions. Subsequently, the current challenges and prospects of utilizing ionic interactions for inducing and modulating the phosphorescent properties are presented. It is anticipated that this perspective will provide basic guidelines for fabricating novel ionic RTP materials and further extend their application potential.

4.
Anal Chim Acta ; 1299: 342452, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38499411

RESUMO

As one of the high pathogenic influenza viruses, H1N1 virus easily induces to serious diseases, even leading to death. To date, all detection methods for H1N1 virus had shortcomings, including high equipment cost, time consumption, and etc. Therefore, a novel detection method should be established to achieve more convenient, rapid, and low-cost detection. In this work, an isomer of HPBmN-I with aggregation-induced emission characteristic was firstly synthesized on the basis of our previous reported HPBpN-I. The results showed that HPBmN-I only selectively binds to N1 in the presence of H1, while HPBpN-I can exhibit total fluorescence response to H1 and N1 in H1/N1 mixture. The limited of detection (LOD) of HPBmN-I to N1 was estimated to be 20.82 ng/mL in normal saline (NS) according to the IUPAC-based approach. The simulation calculations based on molecular docking revealed that four HPBmN-I molecules combine well with the hydrophobic cavity of N1 and achieve the fluorescence enhancement due to size matching with each other. The combination of HPBpN-I and HPBmN-I as probes was successfully used to quantitatively detect H1 and N1 in real H1N1 virus. Compared to enzyme-linked immunosorbent assay (ELISA) method, the established method not only showed the same detection accuracy but also had the advantages of real-time, ease of preparation, and low-cost, demonstrating potential market prospects.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Humanos , Simulação de Acoplamento Molecular , Sensibilidade e Especificidade , Ensaio de Imunoadsorção Enzimática/métodos
5.
Artigo em Inglês | MEDLINE | ID: mdl-38321213

RESUMO

Interstitial cystitis (IC) is a chronic bladder inflammation. Inhibition of prostaglandin G/H synthase 2 (PTGS2) is the most common method for controlling inflammation-related diseases. This study aimed to analyze the effects of hispidulin on the PTGS2 and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammation in experimental IC models. A binding activity between hispidulin and PTGS2 was measured using molecular docking. Human urothelial cells (SV-HUC-1) were stimulated by 2 ng/mL of interleukin (IL)-1ß for 24 h and cultured in a medium with different concentrations of hispidulin (2.5, 5, 10, 20 µM) for 24 h to observe the expressions of PTGS2 and NLRP3 protein. Cells overexpressing PTGS2 were established by PTGS2 cDNA transfection. In the IL-1ß-treated cells, the NLRP3 inflammasome was measured after 20 µM hispidulin treatment. In rats, animals were performed with three injections of 40 mg/kg cyclophosphamide (CYP) and orally treated with 50 mg/kg/day hispidulin or ibuprofen for 3 days. The bladder pain was measured using Von Frey filaments, and the bladder pathology was observed using hematoxylin and eosin (H&E) staining. The expressions of PTGS2 and NLRP3 inflammasome were also observed in the bladder tissues. A good binding activity was found between hispidulin and PTGS2 (score = - 8.9 kcal/mol). The levels of PTGS2 and NLRP3 inflammasome were decreased with the hispidulin dose increase in the IL-1ß-treated cells (p < 0.05). Cells overexpressing PTGS2 weakened the protective effects of hispidulin in the IL-1ß-treated cells (p < 0.01). In the CYP-treated rats, hispidulin treatment improved the bladder pain through decreasing the nociceptive score (p < 0.01) and suppressed the bladder inflammation through suppressing the expressions of PTGS2 and NLRP3 inflammasome in bladder tissues (p < 0.01). Additionally, the results of ibuprofen treatment were similar to the effects of hispidulin in the CYP-treated rats. This study demonstrates that hispidulin may be a new alternative drug for the IC treatment that binds PTGS2 to perform its functions.

6.
Angew Chem Int Ed Engl ; 63(5): e202317431, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38081786

RESUMO

Organic near-infrared room temperature phosphorescence (RTP) materials offer remarkable advantages in bioimaging due to their characteristic time scales and background noise elimination. However, developing near-infrared RTP materials for deep tissue imaging still faces challenges since the small band gap may increase the non-radiative decay, resulting in weak emission and short phosphorescence lifetime. In this study, fused-ring pyrrole-based structures were employed as the guest molecules for the construction of long wavelength emissive RTP materials. Compared to the decrease of the singlet energy level, the triplet energy level showed a more effectively decrease with the increase of the conjugation of the substituent groups. Moreover, the sufficient conjugation of fused ring structures in the guest molecule suppresses the non-radiative decay of triplet excitons. Therefore, a near-infrared RTP material (764 nm) was achieved for deep penetration bioimaging. Tumor cell membrane is used to coat RTP nanoparticles (NPs) to avoid decreasing the RTP performance compared to traditional coating by amphiphilic surfactants. RTP NPs with tumor-targeting properties show favorable phosphorescent properties, superior stability, and excellent biocompatibility. These NPs are applied for time-resolved luminescence imaging to eliminate background interference with excellent tissue penetration. This study provides a practical solution to prepare long-wavelength and long-lifetime organic RTP materials and their applications in bioimaging.


Assuntos
Luminescência , Nanopartículas , Membrana Celular , Pirróis
7.
Angew Chem Int Ed Engl ; 62(50): e202314273, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37885123

RESUMO

The development of flexible, room-temperature phosphorescence (RTP) materials remains challenging owing to the quenching of their unstable triplet excitons via molecular motion. Therefore, a polymer matrix with Tg higher than room temperature is required to prevent polymer segment movement. In this study, a RTP material was developed by incorporating a 4-biphenylboronic acid (BPBA) phosphor into a poly(vinylidene fluoride) (PVDF) matrix (Tg =-27.1 °C), which exhibits a remarkable UV-light-dependent oxygen consumption phosphorescence with a lifetime of 1275.7 ms. The adjustable RTP performance is influenced by the crystallinity and polymorph (α, ß, and γ phases) fraction of PVDF, therefore, the low Tg of the PVDF matrix enables the polymeric segmental motion upon microwave irradiation. Consequently, a reduction in the crystallinity and an increase in the α phase fraction in PVDF film induces RTP after 2.45 GHz microwave irradiation. These findings open up new avenues for constructing crystalline and phase-dependent RTP materials while demonstrating a promising approach toward microwave detection.

8.
Angew Chem Int Ed Engl ; 62(43): e202304838, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37650228

RESUMO

Monitoring the highly dynamic and complex immune response remains a great challenge owing to the lack of reliable and specific approaches. Here, we develop a strategy to monitor the cascade of tumor immune response through the cooperation of pore-forming alginate gel with chemoenzymatic proximity-labeling. A macroporous gel containing tumor-associated antigens, adjuvants, and pro-inflammatory cytokines is utilized to recruit endogenous DCs and enhance their maturation in vivo. The mature DCs are then modified with GDP-fucose-fucosyltransferase (GDP-Fuc-Fuct) via the self-catalysis of fucosyltransferase (Fuct). Following the migration of the obtained Fuct-DCs to the draining lymph nodes (dLNs), the molecular recognition mediated interaction of DCs and T cells leads to the successful decoration of T cells with GDP-Fuc-azide through the Fuct catalyzed proximity-labeling. Therefore, the activated tumor-specific T cells in dLNs and tumors can be identified through bioorthogonal labeling, opening up a new avenue for studying the immune mechanism of tumors in situ.

9.
Proc Natl Acad Sci U S A ; 120(30): e2305187120, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37459543

RESUMO

Genetic alterations are often acquired during prolonged propagation of pluripotent stem cells (PSCs). This ruins the stem cell quality and hampers their full applications. Understanding how PSCs maintain genomic integrity would provide the clues to overcome the hurdle. It has been known that embryonic stem cells (ESCs) utilize high-fidelity pathways to ensure genomic stability, but the underlying mechanisms remain largely elusive. Here, we show that many DNA damage response and repair genes display differential alternative splicing in mouse ESCs compared to differentiated cells. Particularly, Rev1 and Polq, two key genes for mutagenic translesion DNA synthesis (TLS) and microhomology-mediated end joining (MMEJ) repair pathways, respectively, display a significantly higher rate of cryptic exon (CE) inclusion in ESCs. The frequent CE inclusion disrupts the normal protein expressions of REV1 and POLθ, thereby suppressing the mutagenic TLS and MMEJ. Further, we identify an ESC-specific RNA binding protein DPPA5A which stimulates the CE inclusion in Rev1 and Polq. Depletion of DPPA5A in mouse ESCs decreased the CE inclusion of Rev1 and Polq, induced the protein expression, and stimulated the TLS and MMEJ activity. Enforced expression of DPPA5A in NIH3T3 cells displayed reverse effects. Mechanistically, we found that DPPA5A directly regulated CE splicing of Rev1. DPPA5A associates with U2 small nuclear ribonucleoprotein of the spliceosome and binds to the GA-rich motif in the CE of Rev1 to promote CE inclusion. Thus, our study uncovers a mechanism to suppress mutagenic TLS and MMEJ pathways in ESCs.


Assuntos
Mutagênicos , Nucleotidiltransferases , Animais , Camundongos , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Células-Tronco Embrionárias Murinas/metabolismo , Células NIH 3T3 , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , DNA , Dano ao DNA
10.
Clin Cancer Res ; 29(22): 4564-4574, 2023 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-37363992

RESUMO

PURPOSE: This interim report of the GARNET phase I trial presents efficacy and safety of dostarlimab in patients with advanced or recurrent endometrial cancer (EC), with an analysis of tumor biomarkers as prognostic indicators. PATIENTS AND METHODS: A total of 153 patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and 161 patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) EC were enrolled and dosed. Patients received 500 mg dostarlimab every 3 weeks for four cycles, then 1,000 mg every 6 weeks until progression. Primary endpoints were objective response rate (ORR) and duration of response (DOR). RESULTS: A total of 143 patients with dMMR/MSI-H EC and 156 patients with MMRp/MSS EC were evaluated for efficacy. ORR was 45.5% (n = 65) and 15.4% (n = 24) for dMMR/MSI-H EC and MMRp/MSS EC, respectively. Median DOR for dMMR/MSI-H EC was not met (median follow-up, 27.6 months); median DOR for MMRp/MSS EC was 19.4 months. The ORRs by combined positive score (CPS) ≥1 status were 54.9% and 21.7% for dMMR/MSI-H EC and MMRp/MSS EC, respectively. ORRs by high tumor mutational burden (≥10 mutations/Mb) were 47.8% (43/90) and 45.5% (5/11) for dMMR/MSI-H EC and MMRp/MSS EC, respectively. ORR in TP53mut or POLεmut molecular subgroups was 18.1% (17/94) and 40.0% (2/5), respectively. The safety profile of dostarlimab was consistent with previous reports. CONCLUSIONS: Dostarlimab demonstrated durable antitumor activity and safety in patients with dMMR/MSI-H EC. Biomarkers associated with EC may identify patients likely to respond to dostarlimab. See related commentary by Jangra and Dhani, p. 4521.


Assuntos
Neoplasias Colorretais , Neoplasias do Endométrio , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Anticorpos Monoclonais Humanizados , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Neoplasias Colorretais/patologia , Instabilidade de Microssatélites , Biomarcadores Tumorais/genética , Reparo de Erro de Pareamento de DNA
11.
Future Oncol ; 19(25): 1709-1714, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37381977

RESUMO

WHAT IS THIS SUMMARY ABOUT?: Dostarlimab, also known by the brand name JEMPERLI, is a medicine that can be used to treat certain types of endometrial cancer. GARNET is an ongoing phase 1 clinical study that is testing the safety and side effects of dostarlimab and the best way to administer it to patients. The results presented in this summary are from a time point in the middle of the study. WHAT WERE THE RESULTS?: The results from the GARNET study published in 2022 showed how well dostarlimab worked for people participating in the study. Dostarlimab was found to reduce the size of tumors in patients with certain types of endometrial cancer. The patients treated with dostarlimab had side effects that could be managed and few severe side effects. WHAT DO THE RESULTS MEAN?: The results of the GARNET study led to dostarlimab being approved to treat patients with certain types of endometrial cancer. For patients with advanced-stage endometrial cancer, or endometrial cancer that has come back after chemotherapy (recurrent), there are few treatment options. The results suggest that dostarlimab may provide long-term benefits for these patients.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias do Endométrio , Humanos , Feminino , Pacientes , Idioma
12.
Chemistry ; 29(46): e202301035, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37200207

RESUMO

Chiral aggregation-induced emission (AIE) molecules have drawn attention for their helical self-assembly and special optical properties. The helical self-assembly of AIE-active chiral non-linear main-chain polymers can produce some desired optical features. In this work, a series of V-shaped chiral AIE-active polyamides P1-C3, P1-C6, P1-C12 and linear P2-C3, P2-C6, bearing n-propyl/hexyl/dodecyl side-chains, based on tetraphenylbutadiene (TPB), were prepared. All target main-chain polymers exhibit distinct AIE characteristics. The polymer P1-C6 with moderate length alkyl chains shows better AIE properties. The V-shaped main-chains and the chiral induction of (1R,2R)-(+)-1,2-cyclohexanediamine in each repeating unit promote the polymer chains display helical conformation, and multiple helical polymer chains induce nano-fibers helicity when the polymer chains aggregate and self-assemble in THF/H2 O mixtures. Simultaneously, the helical conformation polymer chains and helical nano-fibers cause P1-C6 produce strong circular dichroism (CD) signals with positive Cotton effect. Moreover, P1-C6 could also occur fluorescence quenching response to Fe3+ selectively with a low detection limit of 3.48 µmol/L.

13.
ACS Nano ; 17(8): 7352-7365, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37037487

RESUMO

The intrinsic features and functions of platelets and mesenchymal stem cells (MSCs) indicate their great potential in the treatment of intracerebral hemorrhage (ICH). However, neither of them can completely overcome ICH because of the stealth process and the complex pathology of ICH. Here, we fabricate hybrid cells for versatile and highly efficient ICH therapy by fusing MSCs with platelets and loading with lysophosphatidic acid-modified PbS quantum dots (LPA-QDs). The obtained LPA-QDs@FCs (FCs = fusion cells) not only inherit the capabilities of both platelets and MSCs but also exhibit clearly enhanced proliferation activated by LPA. After systemic administration, many proliferating LPA-QDs@FCs rapidly accumulate in ICH areas for responding to the vascular damage and inflammation and then efficiently prevent both the primary and secondary injuries of ICH but with no obvious side effects. Moreover, the treatment process can be tracked by near-infrared II fluorescence imaging with highly spatiotemporal resolution, providing a promising solution for ICH therapy.


Assuntos
Hemorragia Cerebral , Células-Tronco Mesenquimais , Ratos , Animais , Humanos , Ratos Sprague-Dawley , Células Híbridas/patologia , Proliferação de Células
14.
Chem Commun (Camb) ; 59(36): 5329-5342, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37039234

RESUMO

Organic room-temperature phosphorescence (RTP) materials are currently the focus of research in the field of bioimaging. In comparison with the conventional imaging modalities based on organic fluorescent dyes, RTP materials with long lifetime enable time-resolved imaging to improve the imaging resolution by avoiding autofluorescence. In this review, we will start with summarizing strategies for achieving high performance RTP materials for bioimaging, including the development of RTP-compounds, host-guest doping materials, and supramolecular assemblies. We then discuss the optimization of nanonization processes to obtain RTP nanoparticles with controllable size, high dispersibility, and improved stability. The differences between top-down and bottom-up approaches are further described. Finally, we briefly introduce the emerging methods for preparing RTP materials for bioimaging.


Assuntos
Corantes Fluorescentes , Nanopartículas , Temperatura
15.
J Mater Chem B ; 11(14): 3106-3112, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-36897106

RESUMO

The modulation of triplet exciton decay in organic room-temperature phosphorescence (RTP) materials has been considered as a promising strategy for highly efficient photodynamic therapy. In this study, we report an effective approach based on microfluidic technology to manipulate the triplet exciton decay for generating highly reactive oxygen species (ROS). BQD shows strong phosphorescence upon doping into crystalline BP, indicating the high generation of triplet excitons based on the host-guest interaction. Through microfluidic technology, BP/BQD doping materials can be precisely assembled to form uniform nanoparticles with no phosphorescence but strong ROS generation. The energy decay of the long-lived triplet excitons of BP/BQD nanoparticles emitting phosphorescence has been successfully manipulated via microfluidic technology to generate 20-fold enhanced ROS than that of BP/BQD nanoparticles prepared by nanoprecipitation. The in vitro antibacterial studies indicate that BP/BQD nanoparticles have high specificity against S. aureus microorganisms with a low minimum inhibition concentration (10-7 M). BP/BQD nanoparticles below 300 nm show size-assisted antibacterial activity, demonstrated using a newly developed biophysical model. This novel microfluidic platform provides an efficient approach to convert host-guest RTP materials into photodynamic antibacterial agents and to promote the development of antibacterial agents without cytotoxicity and drug-resistance issues based on the host-guest RTP systems.


Assuntos
Nanopartículas , Fotoquimioterapia , Microfluídica , Espécies Reativas de Oxigênio , Staphylococcus aureus , Antibacterianos/farmacologia
16.
J Phys Chem Lett ; 14(7): 1794-1807, 2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36763033

RESUMO

Small molecular host-guest doped materials exhibit superiority toward high-efficiency room-temperature phosphorescence (RTP) materials due to their structural design diversity and ease of preparation. Dynamic RTP materials display excellent characteristics, such as good reversibility, quick response, and tunable luminescence ability, making them applicable to various cutting-edge technologies. Herein, we summarize the advances in host-guest doped dynamic RTP materials that respond to external and internal stimuli and present some insights into the molecular design strategies and underlying mechanisms. Subsequently, specific viewpoints are described regarding this promising field for the development of dynamic RTP materials. This Perspective is highly beneficial for future intelligent applications of dynamic RTP systems.

17.
ACS Appl Mater Interfaces ; 14(43): 49119-49127, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36256864

RESUMO

The construction of humidity-responsive fluorescent materials with reversibility, specificity, and sensitivity is of great importance for the development of information encryption, fluorescence patterning, and sensors. Nevertheless, to date, the application of these materials has been limited by their slow response rate and nonspecificity. Herein, a humidity-responsive fluorescence system was designed and assembled to achieve a rapid, reversible, and specific moisture response. The system comprised tetra-(4-pyridylphenyl)ethylene (TPE-4Py) as a fluorescent proton acceptor with an aggregation-induced emission (AIE) effect and poly(acrylic acid) (PAA) as a proton donor with an efficient moisture-capturing ability. The fluorescence color and intensity rapidly changed with increasing relative humidity (RH) because of TPE-4Py protonation, and TPE-4Py deprotonation resulted in recovery of the original fluorescence color in low-humidity environments. The proton transfer between the pyridyl group in TPE-4Py and the carboxyl group in PAA was reversible and chemically stable, and the humidity-responsive fluorescence system showed a high response/recovery speed, an obvious color change, good reversibility, and an outstanding specific moisture response. Because of these advantages, diverse applications of this humidity-responsive fluorescence system in transient fluorescent patterning and the encryption of information were also developed and demonstrated.

18.
Small ; 18(40): e2203825, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36071022

RESUMO

Photodynamic immunotherapy is a promising treatment strategy that destroys primary tumors and inhibits the metastasis and relapse of distant tumors. As reactive oxygen species are an intermediary for triggering immune responses, photosensitizers (PSs) that can actively target and efficiently trigger oxidative stress are urgently required. Herein, pyrrolo[3,2-b]pyrrole as an electronic donor is introduced in acceptor-donor-acceptor skeleton PSs (TP-IS1 and TP-IS2) with aggregation-induced emission properties and high absorptivity. Meanwhile, pyrrolo[3,2-b]pyrrole derivatives innovatively prove their ability of type I photoreaction, indicating their promising hypoxia-tolerant advantages. Moreover, M1 macrophages depicting an ultrafast delivery through the cell-to-cell tunneling nanotube pathway emerge to construct TP-IS1@M1 by coating the photosensitizer TP-IS1. Under low concentration of TP-IS1@M1, an effective immune response of TP-IS1@M1 is demonstrated by releasing damage-associated molecular patterns, maturating dendritic cells, and vanishing the distant tumor. These findings reveal insights into developing hypoxia-tolerant PSs and an efficient delivery method with unprecedented performance against tumor metastasis.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Hipóxia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Pirróis , Espécies Reativas de Oxigênio/metabolismo , Recidiva
19.
Nanoscale ; 14(38): 14064-14072, 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36053244

RESUMO

Developing efficient photosensitizers (PSs) that can generate type I reactive oxygen species (ROS) under illumination is considered an effective way to improve photodynamic therapy (PDT) outcomes due to the hypoxic nature of the tumor environment, but also is very challenging. Herein, a new PS of the multiarylpyrrole (MAP) derivative with a typical donor-acceptor structure was synthesized to efficiently generate type I ROS by using an acceptor-shielding strategy in their aggregated state. The enhanced generation mechanism of type I ROS originated from its ultralong triplet lifetime and the narrow singlet-triplet energy gap of the MAP. More importantly, type I ROS can transform protumoral M2 macrophages (M2) into antitumoral M1 macrophages (M1), which showed synergistic immunotherapy in in vivo experiments. Therefore, introducing shielding groups into acceptors provides general guidance for developing efficient PSs in the aggregation state for clinical PDT.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Imunoterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio
20.
Kaohsiung J Med Sci ; 38(6): 530-541, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35258173

RESUMO

Previous studies reported that long noncoding RNA (lncRNA) ZFPM2-AS1 is upregulated in renal cell carcinoma (RCC). However, the biological role of lncRNA ZFPM2-AS1 in RCC has not been explored. In this study, we investigated the role of lncRNA ZFPM2-AS1 in the progression of RCC. Quantitative real-time polymerase chain reaction was used for gene expression analysis, and functional assays including Cell Counting Kit-8 assay, flow cytometry-based apoptosis assay and transwell migration assays were performed to examine the malignant phenotypes. The functional interaction between ZFPM2-AS1 or miR-130A-3P and their targets was detected by dual-luciferase reporter assay. We found that the expressions of ZFPM2-AS1 and ESCO2 were upregulated in RCC tissues and cells, whereas miR-130a-3p was downregulated. The expression level of ZFPM2-AS1 is significantly associated with advanced TNM, distant metastasis, lymphatic metastasis, and a poor overall survival in RCC patients. Silencing ZFPM2-AS1 in RCC cells suppressed cell proliferation, invasion, and migration, and induced cell apoptosis. ZFPM2-AS1 interacted with miR-130A-3P and negatively regulated its expression in RCC cells. We further showed that ESCO2 was a downstream target of miR-130a-3p. Both miR-130a-3p inhibitor and ESCO2 overexpression could rescue the inhibitory effects of ZFPM2-AS1 knockdown in RCC cells. Together, our study demonstrates that ZFPM2-AS1 plays an oncogenic role in RCC progression via the miR-130a-3p/ESCO2 axis.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , RNA Longo não Codificante , Acetiltransferases/genética , Acetiltransferases/metabolismo , Acetiltransferases/farmacologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/genética
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