共查询到20条相似文献,搜索用时 31 毫秒
1.
Haijun Ma Ruoxin Li Haibing Meng Mei Tian Xianhong Zhang Yanling Liu Le Li Jinying Yuan Yen Wei 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(21):2204778
Photosensitizers (PSs) play a key role in the photodynamic therapy (PDT) of tumors. However, commonly used PSs are prone to intrinsic fluorescence aggregation-caused quenching and photobleaching; this drawback severely limits the clinical application of PDT, necessitating new phototheranostic agents. Herein, a multifunctional theranostic nanoplatform (named TTCBTA NP) is designed and constructed to achieve fluorescence monitoring, lysosome-specific targeting, and image-guided PDT. TTCBTA with a twisted conformation and D-A structure is encapsulated in amphiphilic Pluronic F127 to form nanoparticles (NPs) in ultrapure water. The NPs exhibit biocompatibility, high stability, strong near-infrared emission, and desirable reactive oxygen species (ROSs) production capacity. The TTCBTA NPs also show high-efficiency photo-damage, negligible dark toxicity, excellent fluorescent tracing, and high accumulation in lysosome for tumor cells. Furthermore, TTCBTA NPs are used to obtain fluorescence images with good resolution of MCF-7 tumors in xenografted BALB/c nude mice. Crucially, TTCBTA NPs present a strong tumor ablation ability and image-guided PDT effect by generating abundant ROSs upon laser irradiation. These results demonstrate that the TTCBTA NP theranostic nanoplatform may enable highly efficient near-infrared fluorescence image-guided PDT. 相似文献
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Yue Sun Yifan Zhang Ye Gao Pan Wang Gang He Nicholas T. Blum Jing Lin Quanhong Liu Xiaobing Wang Peng Huang 《Advanced materials (Deerfield Beach, Fla.)》2020,32(48):2004481
Simultaneous photodynamic therapy (PDT) and photothermal therapy (PTT) can reduce the risks of drug leakage, body burden, and preparation complexity in traditional combination PDT/PTT. Here, a versatile nanoporphyrin (Pp18-lipos) self-assembled from lipid–purpurin 18 conjugates (Pp18-lipids) and pure lipids is presented. The as-prepared Pp18-lipos with 2 mol% Pp18-lipids can perform effective PDT and fluorescence imaging. The Pp18-lipos with 65 mol% Pp18 can perform potent PTT and photoacoustic imaging. The chelation of Mn2+ endows the Pp18-lipids-Mn2+ a high T1-weighted magnetic resonance imaging contrast. Notably, pretreatment of low-dose PDT facilitates the endocytosis and tumor accumulation of Pp18-lipos, thus achieving synergistic PDT/PTT. Upon exposure to a single 705 nm-laser, the combination of PDT/PTT achieves a significantly higher tumor growth inhibition rate than PDT or PTT alone. In addition, it is found that the synergistic PDT/PTT triggers more potent anti-tumor immune response including tumor infiltration of immune cells and release of related cytokines. 相似文献
4.
Yeneng Dai Fan Zhang Kai Chen Zhiquan Sun Zhihang Wang Yuwen Xue Meixing Li Quli Fan Qingming Shen Qi Zhao 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(22):2206053
The phototheranostics in the second near-infrared window (NIR-II) have proven to be promising for the precise cancer theranostics. However, the non-responsive and “always on” imaging mode lacks the selectivity, leading to the poor diagnosis specificity. Herein, a tumor microenvironment (TME) activated NIR-II phototheranostic nanoplatform (Ag2S-Fe(III)-DBZ Pdots, AFD NPs) is designed based on the principle of Förster resonance energy transfer (FRET). The AFD NPs are fabricated through self-assembly of Ag2S QDs (NIR-II fluorescence probe) and ultra-small semiconductor polymer dots (DBZ Pdots, NIR-II fluorescence quencher) utilizing Fe(III) as coordination nodes. In normal tissues, the AFD NPs maintain in “off” state, due to the FRET between Ag2S QDs and DBZ Pdots. However, the NIR-II fluorescence signal of AFD NPs can be rapidly “turn on” by the overexpressed GSH in tumor tissues, achieving a superior tumor-to-normal tissue (T/NT) signal ratio. Moreover, the released Pdots and reduced Fe(II) ions provide NIR-II photothermal therapy (PTT) and chemodynamic therapy (CDT), respectively. The GSH depletion and NIR-II PTT effect further aggravate CDT mediated oxidative damage toward tumors, achieving the synergistic anti-tumor therapeutic effect. The work provides a promising strategy for the development of TME activated NIR-II phototheranostic nanoprobes. 相似文献
5.
Ge Gao Yao‐Wen Jiang Wei Sun Yuxin Guo Hao‐Ran Jia Xin‐Wang Yu Guang‐Yu Pan Fu‐Gen Wu 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(33)
Photothermal therapy (PTT) usually requires hyperthermia >50 °C for effective tumor ablation, which inevitably induces heating damage to the surrounding normal tissues/organs. Moreover, low tumor retention and high liver accumulation are the two main obstacles that significantly limit the efficacy and safety of many nanomedicines. To solve these problems, a smart albumin‐based tumor microenvironment‐responsive nanoagent is designed via the self‐assembly of human serum albumin (HSA), dc‐IR825 (a cyanine dye and a photothermal agent), and gambogic acid (GA, a heat shock protein 90 (HSP90) inhibitor and an anticancer agent) to realize molecular targeting‐mediated mild‐temperature PTT. The formed HSA/dc‐IR825/GA nanoparticles (NPs) can escape from mitochondria to the cytosol through mitochondrial disruption under near‐infrared (NIR) laser irradiation. Moreover, the GA molecules block the hyperthermia‐induced overexpression of HSP90, achieving the reduced thermoresistance of tumor cells and effective PTT at a mild temperature (<45 °C). Furthermore, HSA/dc‐IR825/GA NPs show pH‐responsive charge reversal, effective tumor accumulation, and negligible liver deposition, ultimately facilitating synergistic mild‐temperature PTT and chemotherapy. Taken together, the NIR‐activated NPs allow the release of molecular drugs more precisely, ablate tumors more effectively, and inhibit cancer metastasis more persistently, which will advance the development of novel mild‐temperature PTT‐based combination strategies. 相似文献
6.
Mitochondria‐Targeting Magnetic Composite Nanoparticles for Enhanced Phototherapy of Cancer
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Ranran Guo Haibao Peng Ye Tian Shun Shen Wuli Yang 《Small (Weinheim an der Bergstrasse, Germany)》2016,12(33):4541-4552
Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities in current days while the high laser power density demand and low tumor accumulation are key obstacles that have greatly restricted their development. Here, magnetic composite nanoparticles for dual‐modal PTT and PDT which have realized enhanced cancer therapeutic effect by mitochondria‐targeting are reported. Integrating PTT agent and photosensitizer together, the composite nanoparticles are able to generate heat and reactive oxygen species (ROS) simultaneously upon near infrared (NIR) laser irradiation. After surface modification of targeting ligands, the composite nanoparticles can be selectively delivered to the mitochondria, which amplify the cancer cell apoptosis induced by hyperthermia and the cytotoxic ROS. In this way, better photo therapeutic effects and much higher cytotoxicity are achieved by utilizing the composite nanoparticles than that treated with the same nanoparticles missing mitochondrial targeting unit at a low laser power density. Guided by NIR fluorescence imaging and magnetic resonance imaging, then these results are confirmed in a humanized orthotropic lung cancer model. The composite nanoparticles demonstrate high tumor accumulation and excellent tumor regression with minimal side effect upon NIR laser exposure. Therefore, the mitochondria‐targeting composite nanoparticles are expected to be an effective phototherapeutic platform in oncotherapy. 相似文献
7.
Hong Xiao Xiaoxia Li Bo Li Shuguang Yang Jingya Qin Shisong Han Jie Ren Xintao Shuai 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(30):2300280
Anticancer immunotherapy is hampered by the poor tumor immunogenicity and immunosuppressive tumor microenvironment (TME). Herein, a liposome nanodrug co-encapsulating doxycycline hydrochloride (Doxy) and chlorin e6 (Ce6) to simultaneously induce autophagy inhibition and mitochondria dysfunction for potentiating tumor photo-immunotherapy is developed. Under near infrared laser irradiation, Ce6 generates cytotoxic reactive oxygen species (ROS) and elicits robust photodynamic therapy (PDT)-induced immunogenic cell death (ICD) for immunosuppressive TME remodeling. In addition, Doxy induced mitochondria dysfunction, which increases ROS generation and enhances PDT to exert more potent killing effect and more powerful ICD. Meanwhile, Doxy increases MHC-I expression on tumor cells surface by efficient autophagy inhibition, leading to more efficient antigen presentation and CTLs recognition to increase tumor immunogenicity. The nanodrugs elicit remarkable antitumor therapy by combining Ce6-mediated PDT and Doxy-induced autophagy inhibition and mitochondria dysfunction. The developed nanodrugs represent a highly efficient strategy for improving cancer immunotherapy. 相似文献
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Zhijun Zhang Wenhan Xu Miaomiao Kang Haifei Wen Heng Guo Pengfei Zhang Lei Xi Kai Li Lei Wang Dong Wang Ben Zhong Tang 《Advanced materials (Deerfield Beach, Fla.)》2020,32(36):2003210
Aiming to achieve versatile phototheranostics with the integrated functionalities of multiple diagnostic imaging and synergistic therapy, the optimum use of dissipated energy through both radiative and nonradiative pathways is definitely appealing, yet a significantly challenging task. To the best of the knowledge, there have been no previous reports on a single molecular species effective at affording all phototheranostic modalities including fluorescence imaging (FLI), photoacoustic imaging (PAI), photothermal imaging (PTI), photodynamic therapy (PDT), and photothermal therapy (PTT). Herein, a simple and highly powerful one-for-all phototheranostics based on aggregation-induced emission (AIE)-active fluorophores is tactfully designed and constructed. Thanks to its strong electron donor–acceptor interaction and finely modulated intramolecular motion, the AIE fluorophore-based nanoparticles simultaneously exhibit bright near-infrared II (NIR-II) fluorescence emission, efficient reactive oxygen species generation, and high photothermal conversion efficiency upon NIR irradiation, indicating the actualization of a balance between radiative and nonradiative energy dissipations. Furthermore, the unprecedented performance on NIR-II FLI-PAI-PTI trimodal-imaging-guided PDT–PTT synergistic therapy is demonstrated by the precise tumor diagnosis and complete tumor elimination outcomes. This study thus brings a new insight into the development of superior versatile phototheranostics for practical cancer theranostics. 相似文献
9.
Yulin Xie Man Wang Yanrong Qian Lei Li Qianqian Sun Minghong Gao Chunxia Li 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(44):2303596
Breaking immunosuppressive tumor microenvironment (TME) has unique effects on inhibiting tumor growth and recurrence. Here, an endoplasmic reticulum (ER) targeted PdPtCu nanozyme (PNBCTER) is prepared to boost immunotherapy. First, PNBCTER has three kinds of enzyme activities, including catalase (CAT), glutathione oxidase (GSHOx), and peroxidase (POD)-like activities, which can reshape the TME. Second, PNBCTER kills tumor cells by photodynamic therapy (PDT) and photothermal therapy (PTT). Third, guided by TER, PNBCTER not only realizes the combination therapy of PDT, PTT and chemodynamic therapy (CDT), but also damages the ER of tumor cells and actives antitumor immune response, which breaks through the immune blockade of TME. Finally, the NLG919 blocks the tryptophan/kynurenine immune escape pathway and reverses the immunosuppressive TME. The strategy that reshaping the TME by enzyme catalysis and breaking immunosuppression provides a novel way for the application of combination therapy in tumor. 相似文献
10.
Raviraj Vankayala Yu‐Kuan Huang Poliraju Kalluru Chi‐Shiun Chiang Kuo Chu Hwang 《Small (Weinheim an der Bergstrasse, Germany)》2014,10(8):1612-1622
Previously, a large volume of papers reports that gold nanorods (Au NRs) are able to effectively kill cancer cells upon high laser doses (usually 808 nm, 1–48 W/cm2) irradiation, leading to hyperthermia‐induced destruction of cancer cells, i.e, photothermal therapy (PTT) effects. Combination of Au NRs‐mediated PTT and organic photosensitizers‐mediated photodynamic therapy (PDT) were also reported to achieve synergistic PTT and PDT effects on killing cancer cells. Herein, we demonstrate for the first time that Au NRs alone can sensitize formation of singlet oxygen (1O2) and exert dramatic PDT effects on complete destrcution of tumors in mice under very low LED/laser doses of single photon NIR (915 nm, <130 mW/cm2) light excitation. By changing the NIR light excitation wavelengths, Au NRs‐mediated phototherapeutic effects can be switched from PDT to PTT or combination of both. Both PDT and PTT effects were confirmed by measurements of reactive oxygen species (ROS) and heat shock protein (HSP 70), singlet oxygen sensor green (SOSG) sensing, and sodium azide quenching in cellular experiments. In vivo mice experiments further show that the PDT effect via irradiation of Au NRs by 915 nm can destruct the B16F0 melanoma tumor in mice far more effectively than doxorubicin (a clinically used anti‐cancer drug) as well as the PTT effect (via irradiation of Au NRs by 780 nm light). In addition, we show that Au NRs can emit single photon‐induced fluorescence to illustrate their in vivo locations/distribution. 相似文献
11.
Ultrastable Near‐Infrared Conjugated‐Polymer Nanoparticles for Dually Photoactive Tumor Inhibition
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Tao Yang Ling Liu Yibin Deng Zhengqing Guo Guobing Zhang Zhishen Ge Hengte Ke Huabing Chen 《Advanced materials (Deerfield Beach, Fla.)》2017,29(31)
It is highly desired that satisfactory photoactive agents with ideal photophysical characteristics are explored for potent cancer phototherapeutics. Herein, bifunctional nanoparticles of low‐bandgap donor–acceptor (D–A)‐type conjugated‐polymer nanoparticles (CP‐NPs) are developed to afford a highly efficient singlet‐to‐triplet transition and photothermal conversion for near‐infrared (NIR) light‐induced photodynamic (PDT)/photothermal (PTT) treatment. CP‐NPs display remarkable NIR absorption with the peak at 782 nm, and perfect resistance to photobleaching. Photoexcited CP‐NPs undergo singlet‐to‐triplet intersystem crossing through charge transfer in the excited D–A system and simultaneous nonradiative decay from the electron‐deficient electron acceptor isoindigo derivative under single‐wavelength NIR light irradiation, leading to distinct singlet oxygen quantum yield and high photothermal conversion efficiency. Moreover, the CP‐NPs display effective cellular uptake and cytoplasmic translocation from lysosomes, as well as effective tumor accumulation, thus promoting severe light‐triggered damage caused by favorable reactive oxygen species (ROS) generation and potent hyperthermia. Thus, CP‐NPs achieve photoactive cell damage through their photoconversion ability for synergistic PDT/PTT treatment with tumor ablation. The proof‐of‐concept design of D–A‐type conjugated‐polymer nanoparticles with ideal photophysical characteristics provides a general approach to afford potent photoactive cancer therapy. 相似文献
12.
Photosensitizer‐Conjugated Albumin−Polypyrrole Nanoparticles for Imaging‐Guided In Vivo Photodynamic/Photothermal Therapy
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Xuejiao Song Chao Liang Hua Gong Qian Chen Chao Wang Zhuang Liu 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(32):3932-3941
Conjugated polymers with strong absorbance in the near‐infrared (NIR) region have been widely explored as photothermal therapy agents due to their excellent photostability and high photothermal conversion efficiency. Herein, polypyrrole (PPy) nanoparticles are fabricated by using bovine serum albumin (BSA) as the stabilizing agent, which if preconjugated with photosensitizer chlorin e6 (Ce6) could offer additional functionalities in both imaging and therapy. The obtained PPy@BSA‐Ce6 nanoparticles exhibit little dark toxicity to cells, and are able to trigger both photodynamic therapy (PDT) and photothermal therapy (PTT). As a fluorescent molecule that in the meantime could form chelate complex with Gd3+, Ce6 in PPy@BSA‐Ce6 nanoparticles after being labeled with Gd3+ enables dual‐modal fluorescence and magnetic resonance (MR) imaging, which illustrate strong tumor uptake of those nanoparticles after intravenous injection into tumor‐bearing mice. In vivo combined PDT and PTT treatment is then carried out after systemic administration of PPy@BSA‐Ce6, achieving a remarkably improved synergistic therapeutic effect compared to PDT or PTT alone. Hence, a rather simple one‐step approach to fabricate multifunctional nanoparticles based on conjugated polymers, which appear to be promising in cancer imaging and combination therapy, is presented. 相似文献
13.
Yiming Zhang Zhijun Ouyang Mengsi Zhan Rui Yang Yue Gao Lulu Li Rui Guo Xiangyang Shi Xueyan Cao 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(39):2301914
Development of intelligent nanoplatforms that can simultaneously target multiple factors associated with tumor growth and metastasis remains an extreme challenge. Here, an intelligent dendritic nanodevice incorporating both copper sulfide nanoparticles (CuS NPs) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA, a vascular disrupting agent) within the dendrimer internal cavities and surface modified with a targeting agent LyP-1 peptide is reported. The resulting generation 5 (G5) dendrimer-based nanodevice, known as G5-PEG-LyP-1-CuS-DMXAA NPs (GLCD NPs), possess good colloidal stability, pH-sensitive drug release kinetics, and high photothermal conversion efficiency (59.3%). These functional GLCD NPs exert a LyP-1-targeted killing effect on breast tumors by combining CuS-mediated photothermal therapy (PTT) and DMXAA-induced vascular disruption, while also triggering antitumor immune responses through PTT-induced immunogenic cell death and DMXAA-mediated immune regulation via M1 polarization of tumor-associated macrophages and dendritic cell maturation. In addition, with the LyP-1-mediated proapoptotic activity, the GLCD NPs can specifically kill tumor lymphatic endothelial cells. The simultaneous disruption of tumor blood vessels and lymphatic vessels cuts off the two main pathways of tumor metastasis, which plays a two-pronged role in inhibiting lung metastasis of the breast cancer model. Thus, the developed GLCD NPs represent an advanced intelligent nanoformulation for immune modulation-mediated combination tumor therapy with potential for clinical translations. 相似文献
14.
Georgy Terentyuk Elizaveta Panfilova Vitaly Khanadeev Daniil Chumakov Elina Genina Alexey Bashkatov Valery Tuchin Alla Bucharskaya Galina Maslyakova Nikolai Khlebtsov Boris Khlebtsov 《Nano Research》2014,7(3):325-337
Nanocomposites (NCs) consisting of a gold nanorod core and a mesoporous silica shell doped with hematoporphyrin (HP) have been fabricated in order to improve the efficiency of cancer treatment by combining photothermal and photodynamic therapies (PDT + PTT) in vivo. In addition to the long-wavelength plasmon resonance near 810-830 nm, the fabricated NCs exhibited a 400-nm absorbance peak corresponding to bound HP, generated singlet oxygen under 633-nm excitation near the 632.5-nm Q-band, and produced heat under a 808-nm near-infrared (NIR) laser irradiation. These modalities were used for a combined PDT + PTT treatment of large (about 3 cm3) solid tumors in vivo with a xenorafted tumor rat model. NCs were directly injected into tumors and irradiated simultaneously with 633-nm and 808-nm lasers to stimulate the combined photodynamic and photothermal activities of NCs. The efficiency of the combined therapy was evaluated by optical coherence tomography, histological analysis, and by measurements of the tumor volume growth during a 21-day period. The NC-mediated PDT led to weak changes in tissue histology and to a moderate 20% decrease in the tumor volume. In contrast, the combined PDT + PTT treatment resulted in the large-area tumor necrosis and led to dramatic decrease in the tumor volume. 相似文献
15.
ACPI Conjugated Gold Nanorods as Nanoplatform for Dual Image Guided Activatable Photodynamic and Photothermal Combined Therapy In Vivo
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Wen‐Xiu Qiu Li‐Han Liu Shi‐Ying Li Qi Lei Guo‐Feng Luo Xian‐Zheng Zhang 《Small (Weinheim an der Bergstrasse, Germany)》2017,13(18)
The nanoplatform GNR‐ACPP‐PpIX (designated as GNR‐ACPI) is designed for dual image guided combined activatable photodynamic therapy (PDT) and photothermal therapy (PTT). In GNR‐ACPI, gold nanorods (GNRs) are modified with a protoporphyrin (PpIX, a PDT agent) conjugated activatable cell penetrating peptide (ACPP), which consists of the matrix metalloproteinases‐2 (MMP‐2) sensitive peptide sequence GPLGLAG. First, the photoactivity of PpIX is effectively quenched by GNRs due to the strong near infrared region light absorption of GNR and the special “U type” structure of ACPP induced close contact between PpIX and GNR. However, once arriving at the tumor site, the GPLGLAG sequence is hydrolyzed by the MMP‐2 overexpressed by tumor cells, resulting in the release of the residual cell membrane penetrating peptide (CPP) attached PpIX (CPP‐PpIX) with the recovery of photoactivity of PpIX. In addition, with the help of CPP, more efficient cellular uptake of PpIX by tumor cells can be achieved, which will greatly improve the PDT efficacy. Moreover, the GNR can also be utilized for photothermic imaging as well as PTT for tumors. It is found that the combination of PTT and PDT under the guidance of dual‐mode imaging greatly enhances the antitumor effects, while possessing negligible systematic toxicity. 相似文献
16.
Mengyu Chang Man Wang Yuhui Liu Min Liu Abdulaziz A. Al Kheraif Ping'an Ma Yanli Zhao Jun Lin 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(10):2206423
The outcome of laser-triggered plasmons-induced phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is significantly limited by the hypoxic tumor microenvironment and the upregulation of heat shock proteins (HSPs) in response to heat stress. Mitochondria, the biological battery of cells, can serve as an important breakthrough to overcome these obstacles. Herein, dendritic triangular pyramidal plasmonic CuPt alloys loaded with heat-sensitive NO donor N, N′-di-sec-butyl-N, N′-dinitroso-1,4-phenylenediamine (BNN) is developed. Under 808 nm laser irradiation, plasmonic CuPt can generate superoxide anion free radicals (·O2−) and heat simultaneously. The heat generated can then trigger the release of NO gas, which not only enables gas therapy but also damages the mitochondrial respiratory chain. Impaired mitochondrial respiration leads to reduced oxygen consumption and insufficient intracellular ATP supply, which effectively alleviates tumor hypoxia and undermines the synthesis of HSPs, in turn boosting plasmonic CuPt-based PDT and mild PTT. Additionally, the generated NO and ·O2− can react to form more cytotoxic peroxynitrite (ONOO−). This work describes a plasmonic CuPt@BNN (CPB) triggered closed-loop NO gas, free radicals, and mild photothermal therapy strategy that is highly effective at reciprocally promoting antitumor outcomes. 相似文献
17.
缺氧作为实体瘤的标志,严重地影响了整体抗肿瘤治疗效果,尤其是光动力疗法.在本文中,我们开发了具有近红外光响应性的类过氧化氢酶纳米囊泡:铂/金纳米壳包覆的二氢卟酚e6(Ce6)/白藜芦醇(Res)脂质体(Pt@Au-Ce6/Res-Lips),以解决这一棘手的问题.Pt@Au-Ce6/Res-Lips可以分解肿瘤微环境中... 相似文献
18.
Nannan Wang Zilong Zhao Yifan Lv Huanhuan Fan Huarong Bai Hongmin Meng Yuqian Long Ting Fu Xiaobing Zhang Weihong Tan 《Nano Research》2014,7(9):1291-1301
Chlorin e6-pHLIPss-AuNRs, a gold nanorod-photosensitizer conjugate containing a pH (low) insertion peptide (pHLIP) with a disulfide bond which imparts extracellular pH (pHe)-driven tumor targeting ability, has been successfully developed for bimodal photodynamic and photothermal therapy. In this bimodal therapy, chlorin e6 (Ce6), a second-generation photosensitizer (PS), is used for photodynamic therapy (PDT). Gold nanorods (AuNRs) are used as a hyperthermia agent for photothermal therapy (PTT) and also as a nanocarrier and quencher of Ce6. pHLIPss is designed as a pile-driven targeting probe to enhance accumulation of Ce6 and AuNRs in cancer cells at low pH. In Ce6- pHLIPss-AuNRs, Ce6 is close to and quenched by AuNRs, causing little PDT effect. When exposed to normal physiological pH 7.4, Ce6-pHLIPs~-AuNRs loosely associate with the cell membrane. However, once exposed to acidic pH 6.2, pHLIP actively inserts into the cell membrane, and the conjugates are translocated into cells. When this occurs, Ce6 separates from the AuNRs as a result of disulfide bond cleavage caused by intracellular glutathione (GSH), and singlet oxygen is produced for PDT upon light irradiation. In addition, as individual PTT agent, AuNRs can enhance the accumulation of PSs in the tumor by the enhanced permeation and retention (EPR) effect. Therefore, as indicated by our data, when exposed to acidic pH, Ce6-pHLIPss-AuNRs can achieve synergistic PTT/PDT bimodality for cancer treatment. 相似文献
19.
Futing Yang Wenjie Yu Qiying Yu Xiyu Liu Chunping Liu Chong Lu Xinghua Liao Yi Liu Na Peng 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(16):2206124
The apoptosis-resistant mechanism of photodynamic therapy (PDT) usually results in limited therapeutic efficacy. The development of new strategies for sensitizing targeted ferroptosis that bypass apoptosis resistance is of great significance to improve the antitumor efficacy of PDT. In this study, a novel amphiphilic copolymer whose main chain contains reactive oxygen species (ROS)-responsive groups and the end of side chains contains triphenylphosphine is synthesized, to encapsulate porphyrinic metal–organic framework PCN-224 via self-assembly which are hydrothermally synthesized by coordination of zirconium (IV) with tetra-kis(4-caboxyphenyl) porphyrin, and loaded carbon monoxide releasing molecule 401 (CORM-401) by their hollow structures (PCN-CORM), and finally, surface-coated with hyaluronic acid. The nanosystem can sequentially localize to mitochondria which is an important target to induce apoptosis and ferroptosis in cancer cells. Upon excitation with near-infrared light, PCN-224 is activated to produce amounts of ROS, and simultaneously triggers the rapid intracellular release of CO. More importantly, the released CO can sensitize ferroptosis and promote apoptosis to significantly enhance the antitumor efficacy of PCN-224 both in vitro and in vivo. These results illustrate that the mitochondria-targeted drug delivery system combined PDT with CO leads to an effective antitumor efficacy, which maybe a promising way to enhance the treatment efficiency of PDT. 相似文献
20.
Photothermal Therapy Generates a Thermal Window of Immunogenic Cell Death in Neuroblastoma
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A thermal “window” of immunogenic cell death (ICD) elicited by nanoparticle‐based photothermal therapy (PTT) in an animal model of neuroblastoma is described. In studies using Prussian blue nanoparticles to administer photothermal therapy (PBNP‐PTT) to established localized tumors in the neuroblastoma model, it is observed that PBNP‐PTT conforms to the “more is better” paradigm, wherein higher doses of PBNP‐PTT generates higher cell/local heating and thereby more cell death, and consequently improved animal survival. However, in vitro analysis of the biochemical correlates of ICD (ATP, high‐motility group box 1, and calreticulin) elicited by PBNP‐PTT demonstrates that PBNP‐PTT triggers a thermal window of ICD. ICD markers are highly expressed within an optimal temperature (thermal dose) window of PBNP‐PTT (63.3–66.4 °C) as compared with higher (83.0–83.5 °C) and lower PBNP‐PTT (50.7–52.7 °C) temperatures, which both yield lower expression. Subsequent vaccination studies in the neuroblastoma model confirm the in vitro findings, wherein PBNP‐PTT administered within the optimal temperature window results in long‐term survival (33.3% at 100 d) compared with PBNP‐PTT administered within the higher (0%) and lower (20%) temperature ranges, and controls (0%). The findings demonstrate a tunable immune response to heat generated by PBNP‐PTT, which should be critically engaged in the administration of PTT for maximizing its therapeutic benefits. 相似文献