JOURNAL OF NANOBIOTECHNOLOGY
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2021
·Vol. 19
·期 1
·1-16
·
IF 10.435
Zhang Li,Fan Yadi,Yang Zhe,Yang Mo,Wong Chun-Yuen
Background Though the combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) appears to be very attractive in cancer treatment, hypoxia and overproduced glutathione (GSH) in the tumor microenvironment (TME) limit their efficacy for further application.Results In this work, a smart hypoxia-irrelevant free radical nanogenerator (AIPH/PDA@CuS/ZIF-8, denoted as APCZ) was synthesized in situ via coating copper sulphide (CuS)-embedded zeolitic imidazolate framework-8 (ZIF-8) on the free radical initiator 2,2′-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH)-loaded polydopamine (PDA). APCZ showed promising GSH-depleting ability and near-infrared (NIR)-II photothermal performance for combined cancer therapy. Once internalized by 4T1 cells, the outer ZIF-8 was rapidly degraded to trigger the release of CuS nanoparticles (NPs), which could react with local GSH and sequentially hydrogen peroxide (H2O2) to form hydroxyl radical (·OH) for CDT. More importantly, the hyperthermia generated by APCZ upon 1064 nm laser excitation not only permitted NIR-II photothermal therapy (PTT) and promoted CDT, but also triggered the decomposition of AIPH to give toxic alkyl radical (·R) for oxygen-independent PDT. Besides, the PDA together with CuS greatly decreased the GSH level and resulted in significantly enhanced PDT/CDT in both normoxic and hypoxic conditions. The tumors could be completely eradicated after 14 days of treatment due to the prominent therapeutic effects of PTT/PDT/CDT. Additionally, the feasibility of APCZ as a photoacoustic (PA) imaging contrast agent was also demonstrated.Conclusion sThe novel APCZ could realize the cooperative amplification effect of free radicals-based therapies by NIR-II light excitation and GSH consumption, and act as a contrast agent to improve PA imaging, holding tremendous potential for efficient diagnosis and treatment of deep-seated and hypoxic tumors.Graphic abstract
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高影响因子
Small
·
2021
·Vol. 17
·期 42
·2102527
·
IF 13.281
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.
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高影响因子
ACS Applied Bio Materials
·
2021
·
IF 0
Yingjie Kong,Yeneng Dai,Dashan Qi,Wenyu Du,Haiyang Ni,Fan Zhang,Honghai Zhao,Qingming Shen,Meixing Li,Quli Fan
An injectable hydrogel sustained drug release system could be a promising technique for in situ treatment. Herein, an injectable hydrogel was prepared for photothermal-chemo therapy of cancer based on the thermosensitive liposomal hydrogel (Lip-Gel). The Lip-Gel system was fabricated by encapsulation of the NIR-II photothermal agent (DPP–BTz) and chemotherapy drugs (GEM) in thermosensitive liposomes and then combined with hydrogel precursor solution. The hydrogel precursor was used as an injectable flowing solution at room temperature and transferred into a cross-linked gel structure at physiological temperature. After being injected into the tumor, DPP–BTz in the Lip-Gel system can generate heat under irradiation of 1064 nm laser, breaking the thermosensitive liposomes and releasing GEM to kill tumor cells. From the treatment results, the Lip-Gel system showed a significant antitumor effect through chemo-/photothermal therapy combination therapy triggered by the NIR-II laser. This work provides a useful scheme for the development of drug delivery and drug treatment directions for local cancer therapy.
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BIOCONJUGATE CHEMISTRY
·
2021
·
IF 4.774
Ruiyi Dai,Xiangrong Peng,Bi Lin,Danyang Xu,Ruichan Lv
In this research, a NIR II luminescence imaging and enhanced chemo-/photothermal therapy system of CuS–DOX–Nd/FA NPs for breast cancer and lymph node tracing under single 808 nm irradiation is proposed. Nd–DTPA molecular cluster with the NIR II imaging effect as the carrier was designed to load the ultrasmall CuS nanoparticles and chemotherapeutic drug doxorubicin hydrochloride (DOX). The composite probe is used for tumor lesion imaging and tracking the breast cancer sentinel lymph nodes with simultaneous chemo-/photothermal therapy (PTT) for breast cancer under the single 808 nm laser. This designed probe not only has high permeability and retention (EPR) targeting effect but also can respond to the tumor microenvironment (TME), realizing more precise and efficient release of DOX at the cancer focus. At the same time, CuS as a drug carrier has a good photothermal therapy effect (photothermal conversion efficiency: 27.9%). The serialized released chemotherapy DOX and synergistic PTT effect can be used to the treat the in situ breast cancer land and simultaneously kill the metastasis cancer. The system made the combined molecular clusters Nd–DTPA achieve NIR II imaging of tumor lesions of breast cancer and lymph node to obtain the integration of diagnosis of the transferred disease for better prognosis. The feasibility of the system had obvious tumor growth inhibition effect with NIR II imaging guided is verified by a series of in vitro and in vivo experiments.
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高影响因子
Biomedical Optics Express
·
2021
·Vol. 12
·期 11
·6984-6994
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IF 3.732
Xinyan Jiang,Xinyan Jiang,Rui Pu,Rui Pu,Cheng Wang,Jiale Xu,Yaohui Tang,Shuhong Qi,Shuhong Qi,Qiuqiang Zhan,Xunbin Wei,Xunbin Wei,Xunbin Wei,Bobo Gu
Acquired brain injury (ABI), which is the umbrella term for all brain injuries, is one of the most dangerous diseases resulting in high morbidity and mortality, making it extremely significant to early diagnosis of ABI. Current methods, which are mainly composed of X-ray computed tomography and magnetic resonance angiography, remain limited in diagnosis of ABI with respect to limited spatial resolution and long scanning times. Here, we reported through-skull fluorescence imaging of mouse cerebral vasculature without craniotomy, utilizing the fluorescence of down-conversion nanoparticles (DCNPs) in the 1.3 - 1.7 μm near-infrared window (NIR-II window). Due to its high spatial resolution of 22.79 μm, the NIR-II fluorescence imaging method could quickly distinguish the brain injury region of mice after performing the stab wound injury (traumatic brain injury) and ischemic stroke (non-traumatic brain injury), enabling it a powerful tool in the noninvasive and early diagnosis of ABI.
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高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 9
·3499-3506
·
IF 6.843
Qi Wang,Jie Cai,Xinrui Niu,Jing Wang,Jiawei Liu,Chen Xie,Wei Huang,Quli Fan
Nanotheranostics, which can provide great insight into cancer therapy, has been deemed as a promising technology to settle the unmet medical needs. The rational design of high performance nanotheranostics with multiple complementary imaging features and satisfactory therapeutic efficacy is particularly valuable. Herein, versatile nanotheranostic agents DPPB-Gd-I NPs were fabricated by using gadolinium-diethylenetriaminepentaacetic acid chelates and an iodine-decorated copolymer as encapsulation matrixes to encapsulate a polymer DPPB through one-step nanoprecipitation. We have demonstrated that such nanoagents are able to efficiently damage tumors under single dose injection and NIR laser illumination conditions due to the enhanced photodynamic therapy and enhanced photothermal therapy (the tumor inhibition rate was as high as 94.5%). Moreover, these nanoagents can be utilized as dual-modal NIR-II fluorescence/magnetic resonance imaging probes for tumor diagnosis with high sensitivity, deep tissue penetration, and excellent spatial resolution. Overall, this work offers a powerful tactic to fabricate high performance nanotheranostics for clinical application.
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高影响因子
Nanoscale
·
2019
·Vol. 11
·期 45
·22079-22088
·
IF 6.97
Xin Wang,Hui Li,Feng Li,Xiaojun Han,Guanying Chen
Lanthanide-doped nanoparticles have long been stereotyped for optical luminescence bioimaging. However, they are known to be unable to produce therapeutic abilities. Here, we describe a lanthanide-based theranostic agent, namely, prussian blue (PB)-coated NaErF4@NaYF4@NaNdF4 core/shell/shell nanocrystals encapsulated in a phospholipid PEG micelle (PEG-CSS@PB), which showed switched imaging and hyperthermia abilities under distinct near infrared (NIR) light activation. The erbium (Er3+)-enriched inner core nanocrystals (NaErF4) enabled the emission of tissue-penetrating luminescence (1525 nm) in the second biological window (NIR-II, 1000–1700 nm), which endowed high-resolution optical imaging of the blood vessels and tumors under ∼980 nm excitation. High neodymium (Nd3+) concentrations in the epitaxial outer NaNdF4 shell introduced maximum cross relaxation processes that converted the absorbed NIR light (∼808 nm) into heat at high efficiencies, thus providing abilities for photothermal therapy (PTT). Importantly, the coated Prussian blue (PB) increased light absorption by about 10-fold compared to the composite free of PB, thus entailing a high light-to-heat conversion efficiency of ∼50.5%. This commensurated with that of well-established gold nanorods. As a result, the PEG-CSS@PB nanoparticles with MTT-determined low toxicities resulted in ∼80% death of HeLa cells at a dose of 600 μg mL−1 under 808 nm laser irradiance (1 W cm−2) for 10 min. Moreover, utilizing the same light dose, a single PTT treatment in tumor-bearing BALB/c mice shrunk the tumor size by ∼12-fold compared to the tumors without treatment. Our results, here, constituted a solid step forward to entitle lanthanide-based nanoparticles as theranostic agents in nanomedicine studies.
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·Vol. 33
·期 29
·2300342
·
IF 19
Ruodan Lan,Jianxun Lv,Duyang Gao,Dehong Hu,Chunchen Liu,Jie Jia,Hairong Zheng,Chengbo Liu,Ping Zhao,Zonghai Sheng
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation. Macrophages accelerate the pathological process of RA through the continuous cell accumulation and secretion of cytokines. Therefore, multiscale visualization of macrophages is of great significance for the early diagnosis of RA. In this work, folate receptor-targeted Cptnc-4F nanoprobes, named FA-CF-NPs, are developed for dual-model molecular imaging of macrophages in RA mouse models. FA-CF-NPs exhibit complementary imaging advantages with high fluorescence sensitivity and resolution in the second near-infrared window (NIR-II) and promising photoacoustic (PA) imaging contrast with deep tissue penetration. The high affinity of the folate ligand on the surface of FA-CF-NPs to macrophages with overexpressed folate receptors ensures the specific targeting function of the nanoprobes for imaging in vivo. FA-CF-NPs are employed to achieve NIR-II fluorescence imaging to accurately localize macrophages in the joint, obtaining a high signal-to-background ratio (SBR) of 15.5. Meanwhile, PA imaging is also performed to observe macrophage distribution in the longitudinal section of the whole joint. Moreover, macrophage infiltration is detected in the joint of RA mice with the absence of RA pathologies such as synovitis and cartilage loss. The results provide an opportunity for in vivo macrophage tracking and early diagnosis of RA.
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Acta Biomaterialia
·
2023
·
IF 9.7
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.
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高影响因子
Coatings
·
2023
·Vol. 13
·期 6
·1037
·
IF 3.4
Yixin Xie,Ji Xu,Hui Jin,Yunfeng Yi,Yuqing Shen,Xiuming Zhang,Xinxin Liu,Yanan Sun,Wei Shi,Yuan He,Dongtao Ge
Recently, the near-infrared-II (NIR-II, 1000–1350 nm) region has been extensively applied in deep-tissue photothermal therapy (PTT) on account of it having stronger tissue penetration and a higher maximum permissible exposure (MPE) than the near-infrared-I (NIR-I, 650–950 nm) region. In this study, we developed a rapid and convenient in situ polymerization strategy to fabricate polypyrrole nanosheets (PPy NSs) within a few minutes using manganese dioxide nanosheets (MnO2NSs) as both the oxidant and the self-sacrificed template. The fabricated PPy NSs exhibited excellent NIR-II absorption, which conferred its high photothermal conversion efficiency (66.01%) at 1064 nm and its photoacoustic (PA) imaging capability. Both in vivo and in vitro studies have shown that that PPy NSs possess good biological safety and excellent PTT efficacy and PA imaging performances. Thus, the as-synthesized PPy NSs could effectively achieve PA imaging-guided photothermal tumor ablation under 1064 nm excitation. Our work provides a novel and promising method for the rapid preparation of PPy NSs without the addition of exogenous oxidants and subsequent template removal, which could be regarded as potential photothermal agents (PTAs) to integrate the diagnosis and treatment of cancer.Keywords:polypyrrole nanosheets;in situ polymerization;near-infrared-II region;photoacoustic imaging;photothermal therapy
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高影响因子
Advanced Optical Materials
·
2023
·Vol. 11
·期 17
·2300378
·
IF 9
Ruiqi Liu,Yihua Qiu,Fengxia Wu,Shuang Duan,Yongkuan Suo,Baisong Chang,Ying Ren,Mei Tian,Hongguang Liu,Zhen Cheng
The second near-infrared biological window two (NIR-II, 1000–1700 nm) imaging has made remarkable achievements in fluorescence imaging of diseases. Here, this work takes advantage of the rich spectral properties of rare-earth doped nanoparticles (RENPs) and their capability to present multiple emission peaks in different luminescence regions simultaneously; novel RENPs are synthesized that have emission peaks in the NIR-II 1000nm (1000–1300 nm) region and enhanced emission in the NIR-IIb (1500–1700 nm) window and are named as NEU-RENPs. These RENPs with new compositions enable a fair comparison to evaluate their imaging performance in NIR-II 1000nm and NIR-IIb regions under the same conditions. The imaging abilities of the resulted nanoparticles in NIR-II 1000 nm and NIR-IIb regions are investigated systematically for local blood vessels, tumor vessels, acute inflammatory vessels, arterial thrombosis, cerebrovascular inflammation, and brain injury models. The results indicate that imaging of NIR-IIb shows higher resolution and sensitivity than that of NIR-II 1000nm , and it has a stronger ability to accurately distinguish normal and pathological tissues. Interestingly, the fuzzy image of NIR-II 1000nm reveals more information about the background structure of the target, which is difficult to be achieved in NIR-IIb imaging. The results prove NEU-RENPs based NIR-IIb imaging is preferable for biomedical applications.
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高影响因子
Advanced Science
·
2023
·
IF 15.1
Jia Huang,Guiming Deng,Shuya Wang,Tianjiao Zhao,Qiaohui Chen,Yuqi Yang,Yongqi Yang,Jinping Zhang,Yayun Nan,Zhaoqian Liu,Ke Cao,Qiong Huang,Kelong Ai
The fast conversion of hydrogen peroxide (H 2 O 2 ) into reactive oxygen species (ROS) at tumor sites is a promising anticancer strategy by manipulating nanomedicines with near-infrared light in the second region (NIR-II). However, this strategy is greatly compromised by the powerful antioxidant capacity of tumors and the limited ROS generation rate of nanomedicines. This dilemma mainly stems from the lack of an effective synthesis method to support high-density copper-based nanocatalysts on the surface of photothermal nanomaterials. Herein, a multifunctional nanoplatform (MCPQZ) with high–density cuprous (Cu 2 O) supported molybdenum disulfide (MoS 2 ) nanoflowers (MC NFs) is developed for the efficient killing of tumors via a potent ROS storm by an innovative method. Under NIR-II light irradiation, the ROS intensity and maximum reaction velocity ( V max ) produced by MC NFs are 21.6 and 33.8 times that of the non–irradiation group in vitro, which is much higher than most current nanomedicines. Moreover, the strong ROS storm in cancer cells is efficiently formed by MCPQZ (increased by 27.8 times compared to the control), thanks to the fact that MCPQZ effectively pre–weakens the multiple antioxidant systems of cancer cells. This work provides a novel insight to solve the bottleneck of ROS-based cancer therapy.
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高影响因子
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