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Journal of Materials Chemistry B · 2022 ·Vol. 10 ·期 10 ·1650-1662 · IF 7.571

Supramolecular J-aggregates of aza-BODIPY by steric and π–π nteractions for NIR-II phototheranostics

Youliang Tian,Dalong Yin,Quan Cheng,Huiping Dang,Changchang Teng,Lifeng Yan

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.

研究领域: 化学 · 材料科学 · 生物医学工程 · 纳米技术
✓ 已验证 DOI PubMed 高影响因子
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ACS Nano · 2024 · IF 15.8

Customized Lanthanide Nanobiohybrids for Noninvasive Precise Phototheranostics of Pulmonary Biofilm Infection

Zhuo Li,Shan Lu,Wenzhen Liu,Zhuo Chen,Yunmei Huang,Xingjun Li,Jiacheng Gong,Xueyuan Chen

A noninvasive strategy for in situ diagnosis and precise treatment of bacterial biofilm infections is highly anticipated but still a great challenge. Currently, no in vivo biofilm-targeted theranostic agent is available. Herein, we fabricated intelligent theranostic alginate lyase (Aly)-NaNdF4 nanohybrids with a 220 nm sunflower-like structure (NaNdF4@DMS-Aly) through an enrichment-encapsulating strategy, which exhibited excellent photothermal conversion efficiency and the second near-infrared (NIR-II) luminescence. Benefiting from the site-specific targeting and biofilm-responsive Aly release from NaNdF4@DMS-Aly, we not only enabled noninvasive diagnosis but also realized Aly-photothermal synergistic therapy and real-time evaluation of therapeutic effect in mice models with Pseudomonas aeruginosa biofilm-induced pulmonary infection. Furthermore, such nanobiohybrids with a sheddable siliceous shell are capable of delaying the NaNdF4 dissolution and biodegradation upon accomplishing the therapy, which is highly beneficial for the biosafety of theranostic agents.

研究领域: 纳米技术 · 生物医学工程 · 药学 · 传染病学 · 材料科学
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JOURNAL OF NANOBIOTECHNOLOGY · 2022 ·Vol. 20 ·期 1 ·1-18 · IF 9.429

Preclinical safety and hepatotoxicity evaluation of biomineralized copper sulfide nanoagents

Xia Ya-Nan,Zu He,Guo Haoxiang,Jiang Tianyan,Yang Siqi,Yu Huan,Zhang Shaodian,Ding Heng,Li Xiaoyu,Wang Yangyun,Wang Yong,Zhang Leshuai W.

Albumin-biomineralized copper sulfide nanoparticles (Cu 2−x S NPs) have attracted much attention as an emerging phototheranostic agent due to their advantages of facile preparation method and high biocompatibility. However, comprehensive preclinical safety evaluation is the only way to meet its further clinical translation. We herein evaluate detailedly the safety and hepatotoxicity of bovine serum albumin-biomineralized Cu 2−x S (BSA@Cu 2−x S) NPs with two different sizes in rats. Large-sized (LNPs, 17.8 nm) and small-sized (SNPs, 2.8 nm) BSA@Cu 2−x S NPs with great near-infrared absorption and photothermal conversion efficiency are firstly obtained. Seven days after a single-dose intravenous administration, SNPs distributed throughout the body are cleared primarily through the feces, while a large amount of LNPs remained in the liver. A 14-day subacute toxicity study with a 28-day recovery period are conducted, showing long-term hepatotoxicity without recovery for LNPs but reversible toxicity for SNPs. Cellular uptake studies indicate that LNPs prefer to reside in Kupffer cells, leading to prolonged and delayed hepatotoxicity even after the cessation of NPs administration, while SNPs have much less Kupffer cell uptake. RNA-sequencing analysis for gene expression indicates that the inflammatory pathway, lipid metabolism pathway, drug metabolism-cytochrome P450 pathway, cholesterol/bile acid metabolism pathway, and copper ion transport/metabolism pathway are compromised in the liver by two sizes of BSA@Cu 2−x S NPs, while only SNPs show a complete recovery of altered gene expression after NPs discontinuation. This study demonstrates that the translational feasibility of small-sized BSA@Cu 2−x S NPs as excellent nanoagents with manageable hepatotoxicity. Graphical Abstract

CAS / MDL: 1310-73-2
研究领域: 纳米技术 · 药理学 · 毒理学 · 分子生物学
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Acta Biomaterialia · 2023 · IF 9.7

Self-delivery of metal-coordinated NIR-II nanoadjuvants for multimodal imaging-guided photothermal-chemodynamic amplified immunotherapy

Yeneng Dai,Xiangyu Li,Yuwen Xue,Kai Chen,Guanda Jiao,Lipeng Zhu,Meixing Li,Quli Fan,Yunlu Dai,Qi Zhao,Qingming Shen

The effectiveness of phototheranostics induced immunotherapy is still hampered by limited light penetration depth, the complex immunosuppressive tumor microenvironment (TME) and the low efficiency of immunomodulator drug delivery. Herein, self-delivery and TME responsive NIR-II phototheranostic nanoadjuvants (NAs) were fabricated to suppress the growth and metastasis of melanoma through the integration of photothermal-chemodynamic therapy (PTT-CDT) and immune remodeling. The NAs were constructed by the self-assembly of ultrasmall NIR-II semiconducting polymer dots and the toll-like receptor agonist resiquimod (R848) utilizing manganese ions (Mn 2+ ) as coordination nodes. Under acidic TME, the NAs responsively disintegrated and released therapeutic components, which enable NIR-II fluorescence/photoacoustic/magnetic resonance imaging-guided tumor PTT-CDT. Moreover, the synergistic treatment of PTT-CDT could induce significant tumor immunogenic cell death and evoke highly efficacious cancer immunosurveillance . The released R848 stimulated the maturation of dendritic cells, which both amplified the antitumor immune response by modulating and remodeling the TME. The NAs present a promising integration strategy of polymer dot-metal ion coordination and immune adjuvants for precise diagnosis and amplified anti-tumor immunotherapy against deep-seated tumors. Statement of significance The efficiency of phototheranostics induced immunotherapy is still limited by insufficient light penetration depth, low immune response and the complex immunosuppressive tumor microenvironment (TME). In order to improve the efficacy of immunotherapy, self-delivery NIR-II phototheranostic nanoadjuvants (PMR NAs) were successfully fabricated via the facile coordination self-assembly of ultra-small NIR-II semiconducting polymer dots and toll-like receptor agonist resiquimod (R848) utilizing manganese ions (Mn 2+ ) as coordination nodes. PMR NAs not only enable TME responsive cargo release and NIR-II fluorescence/photoacoustic/magnetic resonance imaging mediated precise localization of tumors, but also achieve synergistic photothermal-chemodynamic therapy, evoking an effective anti-tumor immune response by ICD effect. The responsively released R848 could further amplify the efficiency of immunotherapy by reversing and remodeling the immunosuppressive tumor microenvironment, thereby effectively inhibiting tumor growth and lung metastasis.

CAS / MDL: 13446-34-9
研究领域: 生物医学工程 · 纳米技术 · 癌症免疫疗法 · 诊疗学 · 免疫学
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Nonfluorescent Near-Infrared Surface-Enhanced Resonance Raman Nanoprobes with Ultrahigh Brightness and Synergistic Photothermal Effect

Caixia Qi,Lin Shen,Jin Li,Xun Sun,Lehui Song,Jiadong Chen,Yixuan Wu,Jaebum Choo,Lingxin Chen

Near-infrared (NIR) surface-enhanced resonance Raman (SERRS) nanoprobes have found wide applications in biomedicine; however, almost all of these nanoprobes are fluorescent because the resonant Raman dyes used cannot be fully quenched onto the underlying plasmonic nanoparticles. Therefore, suppressing the fluorescence backgrounds in resonant Raman spectroscopy imaging is extremely important. In this work, we use a black hole quencher, IQ1, as a Raman dye to develop absolutely nonfluorescent NIR resonant SERRS NPs. Ultrafast spectroscopy clarifies that the nonfluorescent mechanism of the dyes is attributed to the ultrafast internal conversion at the subpicosecond scale, which quenches the fluorescence of excited states. The resultant nanoprobes exhibit zero fluorescent background, femtomolar-level sensitivity (100 fM) as well as superb photostability (τ = 10006 s) without fluorescence photobleaching, outperforming that of fluorescent counterparts. More importantly, the SERRS NPs show a synergistic photothermal effect originating from the dye molecule-plasmon interactions, achieving a high photothermal conversion efficiency of 64.94%. Featuring these excellent properties, these SERRS NPs allow for longitudinally photostable cellular imaging and enhanced photothermal elimination of cancer cells. To the best of our knowledge, this is the first example of absolutely nonfluorescent NIR SERRS NPs, opening up promising applications for improved phototheranostics.

CAS / MDL: 62-31-7
研究领域: 生物医学工程 · 纳米技术 · 光学光谱学 · 癌症治疗
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Small · 2021 ·Vol. 17 ·期 42 ·2102527 · IF 13.281

NIR-II Excitation Phototheranostic Nanomedicine for Fluorescence/Photoacoustic Tumor Imaging and Targeted Photothermal-Photonic Thermodynamic Therapy

Yeneng Dai,Honghai Zhao,Kun He,Wenyu Du,Yingjie Kong,Zhen Wang,Meixing Li,Qingming Shen,Pengfei Sun,Quli Fan

The success of phototheranostics is hampered by some intrinsic defects, such as limited light penetration depth, heat resistance of tumor cells to photothermal therapy (PTT) induced by heat shock protein (HSP) and stress resistance against photodynamic therapy (PDT) caused by hypoxia microenvironment of tumor. Herein, a second near infrared (NIR-II) light excitation phototheranostic nanomedicine has been fabricated by integrating the semiconducting polymer, azo compound, and HSP inhibitor into a thermosensitive liposome, followed by modification with targeting aptamer, forming Lip(PTQ/GA/AIPH) for multimodal phototheranostics of triple-negative breast cancer (TNBC). The phototheranostic nanomedicine provides tumor targeting NIR-II fluorescence and photoacoustic dual-modal imaging, as well as NIR-II PTT. The released HSP inhibitor can effectively inhibit the activity of HSP for enhanced NIR-II PTT. Moreover, azo compound can be decomposed by the NIR-II photothermal activation, generating cytotoxic free radicals and realizing oxygen-irrelevant photonic thermodynamic therapy (PTDT) effects. Under the NIR-II laser irradiation, NIR-II fluorescence/photoacoustic dual-modal imaging guided enhanced NIR-II PTT and PTDT by Lip(PTQ/GA/AIPH), can achieve precise diagnosis and effective suppression of deep-seated TNBC with negligible side effects. This work develops a promising NIR-II excitation phototheranostic nanomedicine for spatiotemporally specific diagnosis and combination therapy of TNBC.

CAS / MDL: 28752-68-3
研究领域: 纳米技术 · 生物医学工程 · 癌症研究 · 诊疗学 · 光学成像
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