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Correction for 'In situ formation of J-aggregate in the tumor microenvironment using acidity responsive polypeptide nanoparticle encapsulating galactose-conjugated BODIPY dye for NIR-II phototheranostics' by Huiping Dang et al., J. Mater. Chem. B, 2022, 10, 5279-5290, https://doi.org/10.1039/D2TB00705C.
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Although differential privacy metaverse data sharing can avoid privacy leakage of sensitive data, randomly perturbing local metaverse data will lead to an imbalance between utility and privacy. Therefore, this work proposed models and algorithms of differential privacy metaverse data sharing using Wasserstein generative adversarial networks (WGAN). Firstly, this study constructed the mathematical model of differential privacy metaverse data sharing by introducing appropriate regularization term related to generated data's discriminant probability into WGAN. Secondly, we established basic model and algorithm for differential privacy metaverse data sharing using WGAN based on the constructed mathematical model, and theoretically analyzed basic algorithm. Thirdly, we established federated model and algorithm for differential privacy metaverse data sharing using WGAN by serialized training based on basic model, and theoretically analyzed federated algorithm. Finally, based on utility and privacy metrics, we conducted a comparative analysis for the basic algorithm of differential privacy metaverse data sharing using WGAN, and experimental results validate theoretical results, which show that algorithms of differential privacy metaverse data sharing using WGAN maintaining equilibrium between privacy and utility.
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Federated learning of deep neural networks has emerged as an evolving paradigm for distributed machine learning, gaining widespread attention due to its ability to update parameters without collecting raw data from users, especially in digital healthcare applications. However, the traditional centralized architecture of federated learning suffers from several problems (e.g., single point of failure, communication bottlenecks, etc.), especially malicious servers inferring gradients and causing gradient leakage. To tackle the above issues, we propose a robust and privacy-preserving decentralized deep federated learning (RPDFL) training scheme. Specifically, we design a novel ring FL structure and a Ring-Allreduce-based data sharing scheme to improve the communication efficiency in RPDFL training. Furthermore, we improve the process of distributing parameters of the Chinese residual theorem to update the execution process of the threshold secret sharing, supporting healthcare edge to drop out during the training process without causing data leakage, and ensuring the robustness of the RPDFL training under the Ring-Allreduce-based data sharing scheme. Security analysis indicates that RPDFL is provable secure. Experiment results show that RPDFL is significantly superior to standard FL methods in terms of model accuracy and convergence, and is suitable for digital healthcare applications.
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With the continuous development of organic materials for optoelectronic devices and biological applications, J-aggregation has attracted a great deal of interest in both dye chemistry and supramolecular chemistry. Except for the characteristic red-shifted absorption and emission, such ordered head-to-tail stacked structures may be accompanied by special properties such as enhanced absorption, narrowed spectral bandwidth, improved photothermal and photodynamic properties, aggregation-induced emission enhancement (AIEE) phenomenon, and so forth. These excellent properties add great potential to J-aggregates for optical imaging and phototherapy in the near-infrared (NIR) region. Despite decades of development, the challenge of rationally designing the molecular structure to adjust intermolecular forces to induce J-aggregation of organic dyes remains significant. In this review, we discuss the formation of J-aggregates in terms of intermolecular interactions and summarize some recent studies on J-aggregation dyes for NIR imaging and phototherapy, to provide a clear direction and reference for designing J-aggregates of near-infrared organic dyes to better enable biological applications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
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Corantes Fluorescentes , Nanopartículas , Corantes Fluorescentes/química , Fototerapia , Imagem Óptica/métodos , Nanopartículas/químicaRESUMO
For photothermal therapy (PTT), the improved targeting can decrease the dosage and promote the therapeutic function of photothermal agents, which would effectively improve the antitumor effect. The tumor microenvironment (TME) and cells are targets in designing intelligent and responsive theranostics. However, most of these schemes have been limited to the traditional visible and first near-infrared (NIR-I) regions, eager to expand to the second near-infrared (NIR-II) window. We designed and synthesized a polyethylene glycol conjugated and disulfide-modified macromolecule fluorophore (MPSS). MPSS could self-assemble into core-shell micelles in an aqueous solution (MPSS-NPS), while the small molecule probes were in a high aggregation arrangement inside the nanoparticle. The pronounced aggregation quenching (ACQ) effect caused them to the "sleeping" state. After entering the tumor cells, the disulfide bonds in MPSS-NPS broke in response to a high concentration of glutathione (GSH) in TME, and the molecule probes were released. The highly aggregated state was effectively alleviated, resulting in distinct absorption enhancement in the near-infrared region. Therefore, the fluorescence signal was recovered, and the photothermal performance was triggered. In vitro and in vivo studies reveal that the Nano-system is efficient for the smart NIR-II fluorescence imaging-guided PTT, even at a low dosage and density of irradiation.
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Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Dissulfetos , Corantes Fluorescentes/química , Glutationa , Humanos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fototerapia , Nanomedicina Teranóstica/métodos , Microambiente TumoralRESUMO
Through the activation of packing arrangements of dyes to modulate their photophysical and/or photochemical properties, not only new NIR-II dyes but tumor-specific NIR-II imaging and therapy can also be achieved. Herein, we designed an acid-responsive polypeptide nanoparticle (P-ipr@Gal) encapsulated with a pH-sensitive amphiphilic polypeptide (P-ipr) as a carrier for the galactose-conjugated BODIPY (Gal-BDP) dye. When P-ipr@Gal NPs are enriched in tumor regions by the EPR effect, the acidic microenvironment (pH 6.4-6.8) promotes the disintegration of P-ipr@Gal nanomicelles and the release of sufficient Gal-BDP. The protonation of the julolidine nitrogen of the Gal-BDP dye switched on the molecular stacking transformation from the H-aggregate to J-aggregate. The J-aggregate significantly enhanced the redshift absorption and emission intensity, which enhanced the fluorescence brightness and photothermal therapeutic effect in the tumor region. We also prepared J-aggregates PAsp@Gal with non-acidic responsive polyaspartic acid benzyl esters (PAsp) encapsulated Gal-BDP, which remained "always-on" with J-aggregate characteristics. The P-ipr@Gal (or PAsp@Gal) J-aggregate has a maximum emission peak redshifted to nearly 1064 nm, with a 3.5-fold increase in the emission intensity compared to the H-aggregate at pH 7.4. Based on the effective accumulation of tumor sites and considerable PCE (>40%), P-ipr@Gal nanoparticles have a lower background and higher tumor background ratio, which makes them a potential NIR-II imaging-guided photothermal therapy agents.
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Nanopartículas , Neoplasias , Compostos de Boro , Corantes , Galactose , Humanos , Nanopartículas/química , Peptídeos , Microambiente TumoralRESUMO
A novel NIR-II small-molecule D-A type organic fluorophore conjugation of triphenylamine, thiophene, and benzo[c,d] indol groups (TPA-Et) with strong electron-donating and accepting groups has been synthesized. The dye shows a significant Stokes shift for efficient fluorescence in the NIR-II region and high photothermal performance. The TPA-Et was then encapsulated by an amphiphilic copolymer P(OEGMA)20-P(Asp)14, and micelles (P@TP) has been prepared with outstanding NIR-II imaging performance, excellent photothermal conversion efficiency (52.5%) under 808 nm laser irradiation, and good photostability. Fluorescence imaging experiments have consistently shown that P@TP can image tiny blood vessels in mice, enrich effectively in the tumor region, and maintain a relatively stable NIR-II fluorescence signal in the tumor area for a long time up to 60 h. In vivo photothermal therapy has a highly significant anticancer effect without tumor recurrence, demonstrating the apparent advantages of P@TP as a NIR nanotheranostic platform in NIR-II imaging-guided photothermal therapy.
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Nanopartículas , Neoplasias , Animais , Elétrons , Corantes Fluorescentes/química , Camundongos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Peptídeos , Fototerapia , Nanomedicina Teranóstica/métodosRESUMO
The existing work has conducted in-depth research and analysis on global differential privacy (GDP) and local differential privacy (LDP) based on information theory. However, the data privacy preserving community does not systematically review and analyze GDP and LDP based on the information-theoretic channel model. To this end, we systematically reviewed GDP and LDP from the perspective of the information-theoretic channel in this survey. First, we presented the privacy threat model under information-theoretic channel. Second, we described and compared the information-theoretic channel models of GDP and LDP. Third, we summarized and analyzed definitions, privacy-utility metrics, properties, and mechanisms of GDP and LDP under their channel models. Finally, we discussed the open problems of GDP and LDP based on different types of information-theoretic channel models according to the above systematic review. Our main contribution provides a systematic survey of channel models, definitions, privacy-utility metrics, properties, and mechanisms for GDP and LDP from the perspective of information-theoretic channel and surveys the differential privacy synthetic data generation application using generative adversarial network and federated learning, respectively. Our work is helpful for systematically understanding the privacy threat model, definitions, privacy-utility metrics, properties, and mechanisms of GDP and LDP from the perspective of information-theoretic channel and promotes in-depth research and analysis of GDP and LDP based on different types of information-theoretic channel models.
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Achieving J-aggregation of a molecule is a fascinating way to construct fluorescent imaging and photothermal therapy agents in the second near-infrared window. Modulation of the balance between intermolecular π-π stacking and steric interactions is an elegant method to acquire J-aggregation dyes. Herein, we succeeded in synthesizing an aza-BODIPY dye with J-aggregation characteristics by introducing steric hindrance (TPA) and a π-bridge (thiophene) in the aza-BODIPY skeleton. In aqueous solutions, supramolecular J-aggregates with a regular lamellar stacking structure could quickly be formed by the dye-templated self-assembly and longer absorption (λmax = 939 nm) and emission (λmax = 1039 nm) bands were observed. After co-assembly of the dye and an amphiphilic polypeptide (POEGMA23-PAsp20), the obtained J-aggregation nanoparticles (J-NPs) with good water solubility and smaller size were more suitable for application in living organisms. In addition, the J-NPs exhibited good stability, considerable photothermal conversion capacity (η = 35.6%), and excellent resistance to pH, H2O2, and photobleaching. In vitro and in vivo experiments revealed that the J-NPs show great NIR-II fluorescence imaging capabilities and anti-tumor effects under 915 nm irradiation (1 W cm-2). This is a rare example of using BODIPY dyes to perform NIR-II fluorescence imaging-guided photothermal therapy under NIR-II irradiation.
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Peróxido de Hidrogênio , Terapia Fototérmica , Compostos de Boro , Corantes , Imagem ÓpticaRESUMO
Fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) holds great promise for in vivo imaging and imaging-guided phototherapy with deep penetration and high spatiotemporal resolution. It is very appealing to obtain NIR-II fluorescent probes through simple procedures and economical substrates. Herein, we developed a D-A-D' structure NIR-II photosensitizer (triphenylamine modified aza-Bodipy, TAB) based on the strong electron-withdrawing nature of borane difluoride azadipyrromethene's center (aza-BODIPY). Subsequently, halogen atoms (Br, I) were introduced to the TAB molecule, and TAB-2Br and TAB-2I were synthesized. Compared to the TAB molecule, a significant redshift in the emission wavelength, ultra-large Stokes shift (>300 nm), and enhanced singlet oxygen production capacity were acquired for the halogenated molecules. After self-assembly of TABs and an amphiphilic polypeptide POEGMA23-PAsp20, the obtained P-TAB, P-TAB-2Br, and P-TAB-2I nanoparticles exhibited excellent water solubility and biocompatibility, remarkable photothermal conversion efficiency (beyond 40%), and good resistance to photobleaching, heat, and H2O2. Under 808 nm laser irradiation, the P-TAB-2I exhibited an efficient photothermal effect and ROS generation in vitro. And in vivo experiments revealed that P-TAB-2I displayed efficient NIR-II fluorescence imaging and remarkable tumor ablation results. All of these results make TAB-2I potential organic probes for clinical NIR-II fluorescence imaging and cancer phototherapy.
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Peróxido de Hidrogênio , Nanopartículas , Compostos de Boro , Linhagem Celular Tumoral , Nanopartículas/química , FototerapiaRESUMO
It is essential to develop novel multifunctional and easily synthesized stable NIR-II fluorescent probes to guide photothermal therapy for tumors. Here, we propose a new strategy to construct boron dipyrromethene (BODIPY) J-aggregates by intermolecular hydrogen bonding (H-bond) and π-π stacking interactions to achieve fluorescence emission in the second near-infrared window (NIR-II, 1000-1700 nm). A novel meso-benzamide galactose hexanoate-BODIPY (Gal-OH-BDP) amphiphilic small molecular dye was synthesized and it formed nanoparticles spontaneously in aqueous solution with a maximum emission wavelength near 1060 nm, which works as a smart nanomedicine for targeting NIR-II imaging-guided photothermal therapy (PTT) of hepatocellular carcinoma. Galactose not only provided hydrogen bonds to regulate the aggregation pattern of the molecules but also effectively targeted hepatocellular carcinoma cells and promoted the formation of well-dispersed nanoparticles of dye molecules due to their hydrophilicity. Moreover, due to high photothermal conversion efficiency (PCE = 55%), Gal-OH-BDP NPs achieve galactose-targeted NIR-II imaging and PTT, which is important for the precise diagnosis and treatment of tumors (Scheme 1). In the present research work, H-bond was introduced for the first time into BODIPY for building J-aggregates to achieve the NIR-II fluorescence.
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Boro , Nanopartículas , Linhagem Celular Tumoral , Fluorescência , Galactose , Ligação de Hidrogênio , Fototerapia , Terapia Fototérmica , Porfobilinogênio/análogos & derivadosRESUMO
Most NIR-II fluorescent dyes, especially polymethine cyanine, face the inevitable self-quenching phenomenon in an aqueous solution. This unacceptable property has severely limited their application in high-resolution biological imaging. Here, a NIR-II macromolecular probe (MPAE) is synthesized through the structure modification of molecule probe and the covalent coupling of an amphiphilic polypeptide, which presents considerable biocompatibility and negligible systemic side effect. The molecule probe's stereo structure and the polymer's conjugation could effectively prevent the π-π stacking, thereby exhibiting excellent quenching resistance in aqueous solutions (absolute QY = 0.178%). This remarkable feature endows it with deeper tissue penetration than the clinically used indocyanine green (ICG) and high contrast brightness at the tumor site for the NIR-II fluorescence imaging. Based on the effective accumulation of tumor sites and considerable photothermal conversion efficiency (40.07%), the MPAE-NPS presents superior antitumor efficiency on breast tumor-bearing mice under the 1064 nm irradiation without rebound or recurrence. All these outstanding performances reveal the great promise of MPAE-NPS in Nano-drug delivery and imaging-assisted photothermal therapy in the NIR-II window.
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Nanopartículas , Terapia Fototérmica , Animais , Linhagem Celular Tumoral , Corantes Fluorescentes , Verde de Indocianina , Camundongos , Imagem Óptica , FototerapiaRESUMO
To achieve accurate fluorescence imaging-guided cancer therapy, intelligent systems with specific responsiveness to the tumor microenvironment need to be designed. Here, we have achieved both enhanced NIR fluorescence and photodynamic therapy by introducing a dimethylamino functional group in BODIPY dyes, which can be used as a pH sensor under acidic conditions by coordinating with the proton. At pH 7.4, the fluorescence is quenched due to the photo-induced electron transfer (PET) process. After the photosensitizer is protonated in tumor cell lysosomes (pH 4.0-5.5), the PET process is inhibited and the fluorophore emission capacity is restored (fluorescence enhancement up to 10-fold), resulting in near-infrared fluorescence with the OFF/ON transition inside the tumor and enhanced singlet oxygen production for lysosome targeting capability. Due to the substitution of heavy atom iodine, the compound has a high singlet oxygen quantum yield of 81.8% in dichloromethane. In addition, using a pH-sensitive amphiphilic polypeptide (POEGMA23-PE9) as a carrier to wrap the photosensitizer BDPI can release enough drug in the acidic environment (pH 5.5-6.5) of intracellular endosomes/lysosomes, which is conducive to more adequate interactions of the photosensitizer with H+ and more effective enhancement of fluorescence emission and 1O2 production, achieving precise fluorescence imaging capability and extremely low background toxicity.
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Antineoplásicos/farmacologia , Compostos de Boro/farmacologia , Fluorescência , Nanopartículas/química , Peptídeos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Boro/química , Cápsulas/química , Proliferação de Células/efeitos dos fármacos , Dimetilaminas/química , Dimetilaminas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Lisossomos/metabolismo , Camundongos , Peptídeos/síntese química , Peptídeos/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica , Células Tumorais CultivadasRESUMO
BACKGROUND: Osteosarcoma (OS) is the most common aggressive bone tumor in children and teenagers. Doxorubicin (DOX) is a chemotherapeutic drug for OS. This study aims to reveal the effects and underneath mechanism of DOX treatment in OS progression. METHODS: The expression of circular_0000006 (circ_0000006), microRNA-646 (miR-646) and brain-derived neurotrophic factor (BDNF) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). BDNF protein expression was determined by western blot. Cell proliferation was illustrated by cell counting kit-8 (CCK-8) and cell colony formation assays. Cell migration and invasion were revealed by transwell migration and wound-healing assays and transwell invasion assay, respectively. Cell apoptosis was demonstrated by flow cytometry analysis. The binding relationship of miR-646 and circ_0000006 or BDNF was predicted by circRNA interactome and targetscan online database, respectively, and verified by dual-luciferase reporter assay. The effects of circ_0000006 knockdown on tumor growth in vivo were manifested by in vivo tumor formation assay. RESULTS: Circ_0000006 expression and the mRNA and protein levels of BDNF were dramatically upregulated, and miR-646 expression was effectively downregulated in OS tissues or cells compared with control groups. Circ_0000006 expression and BDNF protein expression were lower, and miR-646 expression was higher in DOX treatment groups than in control groups in OS cells. Circ_0000006 knockdown repressed cell proliferation, migration and invasion, whereas promoted cell apoptosis under DOX treatment in OS cells; however, these effects were attenuated by miR-646 inhibitor. Additionally, circ_0000006 sponged miR-646 to bind to BDNF. Circ_0000006 silencing suppressed tumor growth in vivo. CONCLUSION: Circ_0000006 knockdown promoted DOX-mediated effects on OS development by miR-646/BDNF pathway, which provided a theoretical basis in treating OS with DOX.
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Osteossarcoma , Fator Neurotrófico Derivado do Encéfalo/genética , Progressão da Doença , Doxorrubicina/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , RNA CircularRESUMO
Due to the hydrophobicity of the cyanine dye and the huge conjugated plane, the cyanine dye is prone to H-aggregation in aqueous solution, and the ultraviolet absorption is blue-shifted. Here, a hydrophilic quaternary stereo-specific cyanine (HQS-Cy) dye has been synthesized and polypeptide based nanoparticles have been prepared, which improve the water solubility of the cyanine in two aspects. First, at the molecular level, the sulfonic acid group increases the water solubility of the dye molecule while the dimethyl-ammonium functional group repels the molecule through the charge-charge interaction, destroying the planar characteristics of the cyanine structure, increasing the molecular distance between the dye molecules, and preventing the accumulation of cyanine. Secondly, at the nano-micelle level, the use of amphiphilic polypeptide blocks to encapsulate the dye increases the water solubility of the dye while also increasing its biocompatibility. The HQS-Cy@P NPs prepared by the above methods exhibit the maximum absorption at 985 nm and maximum fluorescence emission at 1050 nm in aqueous solution. HQS-Cy@P exhibits good photothermal stability and significant photothermal conversion efficiency of about 35.5%, and both in vitro and in vivo studies revealed that it is an efficient system for NIR-II imaging-guided photothermal therapy of cancer.
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Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Carbocianinas/farmacologia , Corantes/farmacologia , Terapia Fototérmica , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/diagnóstico por imagem , Carbocianinas/síntese química , Carbocianinas/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Corantes/síntese química , Corantes/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Raios Infravermelhos , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Imagem Óptica , Solubilidade , Neoplasias do Colo do Útero/diagnóstico por imagemRESUMO
NIR-II fluorescence imaging-guided photothermal therapy is a potential tumor therapeutic that has exhibited accurate diagnosis and noninvasive therapy of tumors. Here, we developed an organic macromolecular nanoparticle (PFD) by encapsulating a fluorophore with an amphiphilic polypeptide. The PFD nanoparticle presented a uniform size of 70 nm with a slightly negative charge and exhibited superior photothermal conversion efficiency (40.69%), thermal imaging ability, and considerable photothermal stability. The PFD nanoparticle could accumulate at the tumor site by an enhanced penetration and retention effect and exhibited satisfactory fluorescence imaging and prominent photothermal inhibition effect. In vivo experiments demonstrated that PFD nanoparticles exhibited a prominent photothermal inhibition effect against the tumor. Meanwhile, the therapeutic procedure was monitored by both NIR-II fluorescence and infrared thermal imaging, which demonstrated that the PFD nanoparticles have a potential application in imaging-guided photothermal therapy of tumors.
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Mannose has been reported as a novel drug to kill cancer cells. The prodrug of mannose will promote its targeted delivery and enrichment at the tumor site and cancer cells. Here, a pH-sensitive polypeptide copolymer with a tertiary amine group has been prepared and a mannose molecule was conjugated to the polymer through the formation of a Schiff base. At the same time, an iodinated boron dipyrromethene (BDPI) photosensitizer with high singlet oxygen generation efficacy and near infrared (NIR) fluorescence was encapsulated by the nanoparticles, which makes it a potential pH-sensitive NIR imaging-guided chemotherapy/PDT agent. In vitro and in vivo studies reveal that in a tumor acidic environment, the protonation of the tertiary amine group destroyed the nanostructure of the nanoparticles, resulting in increased BDPI release. Meanwhile, the bond cleavage of the Schiff base led to the release of conjugated mannose and synergistic inhibition of tumor cell growth with the PDT effect was realized. The combination of these two kinds of tumor suppression effects and photodynamic therapy made this pH-sensitive polypeptide delivery system show great potential for further cancer therapy.
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Raios Infravermelhos/uso terapêutico , Manose/uso terapêutico , Nanopartículas/química , Fotoquimioterapia/métodos , Polímeros/química , Pró-Fármacos/uso terapêutico , Animais , Humanos , Manose/farmacologia , Camundongos , Pró-Fármacos/farmacologiaRESUMO
Tumor environmental sensitive polypeptide integrated photosensitizer is a platform for imaging-guided photodynamic therapy (PDT). However, the photosensitizer leakage during blood circulation, poor accumulation in tumor tissue and inferior quantum yield of singlet oxygen are still challenges. Herein, NHS-active boron-dipyrromethene derivative with bromine substituted NHS-BODIPY-Br2 was first synthesized, which possessed high singlet oxygen generation efficiency and near infrared (NIR) fluorescence, and then it was conjugated to a sharp pH (6.36) sensitive polypeptide to achieve a macrophotosensitizer for NIR imaging-guided PDT. In vitro study showed that the macrophotosensitizer nanoparticles exhibited good cellular uptake and ability to kill cancer cells. Once accumulating in the tumor tissues, the nanoparticles can be demicellized by tumor acidity to promote cellular uptake, which could enlarge fluorescence signal intensity and enhance in vivo PDT therapeutic effect upon NIR laser irradiation. It provides a strategy to design photosensitizer conjugated tumor acidity sensitive polypeptide for NIR imaging-guided photodynamic therapy.
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Neoplasias da Mama/terapia , Carcinoma Hepatocelular/terapia , Raios Infravermelhos , Neoplasias Hepáticas/terapia , Fragmentos de Peptídeos/administração & dosagem , Fotoquimioterapia , Radioterapia Guiada por Imagem , Animais , Apoptose , Compostos de Boro/química , Neoplasias da Mama/patologia , Carcinoma Hepatocelular/patologia , Proliferação de Células , Feminino , Humanos , Concentração de Íons de Hidrogênio , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/administração & dosagem , Nanopartículas/química , Oxigênio Singlete , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Efficient delivery of hydrophobic photosensitizer (PS) into tumor cells is a key step for photodynamic therapy (PDT). Redox-responsive polymeric nanoparticles of amphiphilic macro-photosensitizer has designed and prepared as a prodrug-like pro-photosensitizer (pro-PS) for PDT. PEG works as the hydrophilic block and the near infrared (NIR) brominated BODIPY derivative (BDP) works as the hydrophobic PS, and they were linked via the disulfide bond as PEG-SS-BDP, which could be broken for drug release owing to the high GSH concentration inside tumor cells. The amphiphilic PEG-SS-BDP can be self-assembled into polymeric micelles with suitable size (about 110â¯nm), which benefits prolonged blood circulation and enhanced tumor accumulation confirmed by NIR fluorescent imaging in vivo. The higher efficiency of PEG-SS-BDP nanoparticles (PSSBDP NPs) than non-responsive PDT agent (PEG-BDP) with similar structure was confirmed by both in vitro and in vivo studies, suggesting the advantages of the redox-responsive pro-PS system for improving potential near infrared tumor imaging and photodynamic therapy.
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Compostos de Boro/administração & dosagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Polietilenoglicóis/química , Animais , Compostos de Boro/química , Compostos de Boro/farmacocinética , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Raios Infravermelhos , Camundongos , Camundongos Endogâmicos BALB C , Micelas , Nanopartículas , Neoplasias/tratamento farmacológico , Oxirredução , Tamanho da Partícula , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacocinética , Polímeros/química , Pró-FármacosRESUMO
Precise detection of the tumor environment for cancer diagnosis has been strongly demanded for further therapies. Here, a redox-responsive fluorescence switch off/on system PCQ was designed and synthesized conjugated with near-infrared (NIR) cyanine dyes (Cy5.5) and relevant quencher (FQ) in mixed polymeric micelles (PCy and PFQ). The mixed PCQ micelles were prepared with two kinds of polymers with poly(oligo (ethylene glycol) methacrylate) (POEGMA) as the hydrophilic shell, in which fluorescence emission was quenched by fluorescence resonance energy transfer (FRET) effect. The FQ was conjugated with POEGMA by disulfide linkage, which could be broken with a redox environment such as high glutathione (GSH) concentration in tumor cells. After the PCQ micelles got into tumor cells, PFQ blocks in PCQ would be disassembled to recompose PCy micelles. During that process, drugs like doxorubicin (DOX) could be loaded inside and formed PCQ@DOX nanoparticles and then released for accurate NIR bioimaging and drug delivery instantly.