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- 摘要
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- 实验方案
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Hyperthermia and Controllable Free Radicals Co-Enhanced Synergistic Therapy in Hypoxia Enabled by Near-Infrared-II Light Irradiation
摘要: Tumor cells metabolism and tumor blood vessels proliferation represent in a distinctive way compared to normal cells. The resulting tumor microenvironment will presents a characteristic of hypoxia, which greatly limits the generation of oxygen free radicals and affects the therapeutic effect of photodynamic therapy. Here, we developed an oxygen-independent free radicals generated nanosystem (CuFeSe2-AIPH@BSA) with dual-peak absorption in both near-infrared (NIR) regions and utilized it for imaging-guided synergistic treatment. The special absorption endows the nanosystem with high photothermal conversion efficiency and favorably matched photoactivity in both (I and II) NIR biological windows. Upon NIR light irradiation, the generated heat could prompt AIPH release and decompose, and then to produce oxygen-independent free radicals for killing cancer cells effectively. The contrastive research results show the enhanced therapeutic efficacy of NIR-II over NIR-I principally due to its deeper tissue penetration and higher maximum permission exposure benefited from longer wavelength. Hyperthermia effect and the production of toxic free radicals upon NIR-II laser illumination are extremely effective in triggering apoptosis and death of cancer cells in tumor hypoxia microenvironment. The high biocompatibility and excellent anti-cancer efficiency of CuFeSe2-AIPH@BSA allow it to be an ideal oxygen-independent nanosystem for imaging-guided and NIR-II-mediated synergistic therapy via systemic administration.
关键词: second near-infrared window,free radicals,photothermal,hypoxia,oxygen-independent,CuFeSe2
更新于2025-09-19 17:13:59
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Biomineralization-inspired nanozyme for single-wavelength laser activated photothermal-photodynamic synergistic treatment against hypoxic tumors
摘要: Hypoxia, one of the features of most solid tumors, can severely impede the efficiency of oxygen-dependent treatments such as chemotherapy, radiotherapy and type-II photodynamic therapy. Herein, a catalase-like nanozyme RuO2@BSA (RB) was first prepared through a biomineralization strategy, and a high efficiency near-infrared photosensitizer (IR-808-Br2) was further loaded into the protein shell to generate the safe and versatile RuO2@BSA@IR-808-Br2 (RBIR) for the imaging-guided enhanced phototherapy against hypoxic tumors. RB not only acts like a catalase, but also serves as a photothermal agent that speeds up the oxygen supply under near-infrared irradiation (808 nm). The loaded NIR photosensitizer could immediately convert molecular oxygen (O2) to cytotoxic singlet oxygen (1O2) upon the same laser irradiation. Results indicated that RBIR achieved enhanced therapeutic outcomes with negligible side effects. Features such as a simple synthetic route and imaging-guided and single-wavelength-excited phototherapy make the nanozyme a promising agent for clinical applications.
关键词: biomineralization,solid tumors,photodynamic therapy,IR-808-Br2,photothermal therapy,nanozyme,RuO2@BSA,hypoxia
更新于2025-09-19 17:13:59
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Solution‐Processed High‐Quality Cu <sub/>2</sub> O Thin Films as Hole Transport Layers for Pushing the Conversion Efficiency Limit of Cu <sub/>2</sub> O/Si Heterojunction Solar Cells
摘要: In order to discover novel hypoxia-inducible factor 1 (HIF-1) inhibitors for the cancer metastasis treatment, 68 new aryl carboxamide compounds were synthesized and evaluated for their inhibitory effect by dual luciferase-reporter assay. Based on five rounds of investigation on structure?activity relationships step by step, compound 30m was discovered as the most active inhibitor (IC50 = 0.32 μM) with no obvious cytotoxicity (CC50 > 50 μM). It effectively attenuated hypoxia-induced HIF-1α protein accumulation and reduced transcription of vascular epidermal growth factor in a dose-dependent manner, which was further demonstrated by its inhibitory potency on capillary-like tube formation, angiogenesis of zebrafish as well as cellular migration and invasion. Importantly, compound 30m exhibited antimetastatic potency in breast cancer lung metastasis in the mice model, indicating its promising therapeutic potential for prevention and treatment of tumor metastasis. These results definitely merit attention for further rational design of more efficient HIF-1 inhibitors in the future.
关键词: structure?activity relationships,aryl carboxamide derivatives,cancer metastasis,HIF-1 inhibitors,hypoxia-inducible factor 1
更新于2025-09-19 17:13:59
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Phase‐Change Materials Based Nanoparticles for Controlled Hypoxia Modulation and Enhanced Phototherapy
摘要: Tumor hypoxia strengthens tumor resistance to different therapies especially oxygen involved strategies, such as photodynamic therapy (PDT). Herein, the thermal responsive phase change materials (PCM) are utilized to coencapsulate ultrasmall manganese dioxide (sMnO2) and organic photosensitizer IR780 to obtain IR780-sMnO2-PCM nanoparticles for controlled tumor hypoxia modulation and enhanced phototherapy. The thermal responsive protective PCM layer can not only prevent IR780 from photodegradation, but also immediately release sMnO2 to decompose endogenous H2O2 and generate enough oxygen for PDT under laser irradiation. Owing to the efficient accumulation of IR780-sMnO2-PCM nanoparticles in tumor under intravenous injection as revealed by both florescence imaging and photoacoustic imaging, the tumor hypoxia is greatly relieved. Furthermore, in vivo combined photothermal therapy (PTT) and PDT, IR780-sMnO2-PCM nanoparticles, compared to IR780-PCM nanoparticles, exhibit better performance in inhibiting tumor growth. The results highlight the promise of IR780-sMnO2-PCM in controlled modulation of tumor hypoxia to overcome current limitations of cancer therapies.
关键词: hypoxia modulation,cancer theranostics,photodynamic therapy,phase change materials
更新于2025-09-11 14:15:04
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Radiology, Lasers, Nanoparticles and Prosthetics || 8. Cell cycle and cancer
摘要: The present chapter is intended to provide a basic understanding of the cell’s life cycle and the difference between normal and cancerous cells. This information is a prerequisite for the rationale behind cancer treatment plans using radiotherapy discussed in Chapters 9–12. For more specific and detailed information on cell cycle the reader is referred to standard biology [1] or physiology textbooks listed under “Further reading”. Here we focus the discussion on the relation between dose and cell survival rate that is contextual information for the following chapters on radiotherapy.
关键词: radiation response,biological effectiveness,cell cycle,DNA replication,mitosis,oncogenes,apoptosis,tumor suppressors,fractionation,hypoxia,chemotherapy,radiotherapy,cancer
更新于2025-09-11 14:15:04
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Comparative Effects of Coenzyme Q10 or n-3 Polyunsaturated Fatty Acid Supplementation on Retinal Angiogenesis in a Rat Model of Oxygen-Induced Retinopathy
摘要: Neonatal intermittent hypoxia (IH) or apnea afflicts 70% to 90% of all preterm infants <28 weeks gestation, and is associated with severe retinopathy of prematurity (ROP). We tested the hypotheses that coenzyme Q10 (CoQ10) or omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation during neonatal IH reduces the severity of oxygen-induced retinopathy (OIR). Newborn rats were exposed to two IH paradigms: (1) 50% O2 with brief hypoxia (12% O2); or (2) 21% O2 with brief hypoxia, until postnatal day 14 (P14), during which they received daily oral CoQ10 in olive oil, n-3 PUFAs in fish oil, or olive oil only and compared to room air (RA) treated groups. Pups were examined at P14, or placed in RA until P21. Retinal angiogenesis, histopathology, and morphometry were determined. Both IH paradigms produced severe OIR, but these were worsened with 50/12% O2 IH. CoQ10 and n-3 PUFAs reduced the severity of OIR, as well as ocular growth factors in both IH paradigms, but CoQ10 was more effective in 50/12% O2 IH. Supplementation with either CoQ10 or n-3 PUFAs targeting IH-induced retinal injury is individually effective for ameliorating specific characteristics consistent with ROP. Given the complexity of ROP, further studies are needed to determine whether combined CoQ10 and n-3 PUFAs supplementation would optimize their efficacy and result in a better outcome.
关键词: n-3 polyunsaturated fatty acids,oxygen-induced retinopathy,insulin-like growth factor-I,coenzyme Q10,vascular endothelial growth factor,neonatal intermittent hypoxia
更新于2025-09-10 09:29:36
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Arterial Oxygen Saturation, Pulse Oximetry, and Cerebral and Tissue Oximetry in Hypobaric Hypoxia
摘要: Clinical accuracy of pulse oximeters (giving Spo2) is routinely tested down to an Sao2 of 70%, but lower oxygen saturations are often experienced during hypobaric hypoxia. Cerebral (Sco2) and peripheral tissue (Sto2) oxygen saturations can be measured using near infra-red spectroscopy. In a project simulating oxygen system failure during high altitude-high opening parachuting (HAHO), Sao2, Spo2, Sco2, and forearm Sto2 were measured. The aim of the present analysis was to explore the agreement between Sao2 and the three noninvasive measurements of hypoxemia (Spo2, Sco2, and Sto2).
关键词: blood gas analysis,hypoxia,atmospheric pressure,oximetry
更新于2025-09-10 09:29:36
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A two-photon excited O2-Evolving Nanocomposite for Efficient Photodynamic Therapy against hypoxic tumor
摘要: This paper reported on a two-photon excited nanocomposite FCRH to overcome tumor hypoxia for enhanced photodynamic therapy (PDT). Through modified by ruthenium (Ⅱ) complex (Ru(bpy)3 2+) and hyperbranched conjugated copolymer with poly (ethylene glycol) arms (HOP), the water-splitting mediated O2 generation from iron-doped carbon nitride (Fe-C3N4) can be triggered via two-photon irradiation for the first time. While exposured to two-photon laser, Ru(bpy)3 2+ was activated to generate singlet oxygen (1O2) and Fe-C3N4 was triggered to split water for oxygen supply in the mean time. Owing to the injection of photoinduced electrons from excited Ru(bpy)3 2+ to Fe-C3N4, O2 generated by Fe-C3N4 was significantly accelerated. After accumulation of the nanocomposite by enhanced permeability and retention (EPR) effect, FCRH was demonstrated to alleviate the tumorous hypoxia and consequently enhance the antitumor efficacy of PDT. Furthermore, tumor metabolism evaluations explained the capability of the nanocomposite in reducing intratumoral hypoxia. Our results provide a new diagram for ameliorating the hypoxic tumor microenvironment and accelerating 1O2 generation under two-photon excitation, which will find great potential for spatiotemporally controlled tumor treatment in vivo.
关键词: two-photon,water splitting,oxygen generation,tumor hypoxia,photodynamic therapy
更新于2025-09-04 15:30:14
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Hypoxia-Triggered Transforming Immunomodulator for Cancer Immunotherapy via Photodynamically Enhanced Antigen Presentation of Dendritic Cell
摘要: A key factor for successful cancer immunotherapy (CIT) is the extent of antigen presentation by dendritic cells (DCs) that phagocytize tumor-associated antigens (TAA) in the tumor site and migrate to tumor draining lymph nodes (TDLN), for the activation of T cells. Although various types of adjuvant delivery have been studied to enhance the activity of the DCs, poor delivery efficiency and depleted population of tumor infiltrating DCs have limited the efficacy of CIT. Herein, we report a hypoxia-responsive mesoporous silica nanocarrier (denoted as CAGE) for an enhanced CIT assisted by photodynamic therapy (PDT). In this study, CAGE was designed as a hypoxia-responsive transforming carrier to improve the intracellular uptake of nanocarriers and the delivery of adjuvants to DCs. Furthermore, PDT was exploited for the generation of immunogenic debris and recruitment of DCs in a tumor site, followed by enhanced antigen presentation. Finally, a significant inhibition of tumor growth was observed in vivo, signifying that the PDT would be a promising solution for DC-based immunotherapy.
关键词: combinatorial immunotherapy,hypoxia-responsive drug delivery,tumor-associated antigen,dendritic cell modulation,photodynamic therapy
更新于2025-09-04 15:30:14
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Functional Polymer Nanocarriers for Photodynamic Therapy
摘要: Photodynamic therapy (PDT) is an appealing therapeutic modality in management of some solid tumors and other diseases for its minimal invasion and non-systemic toxicity. However, the hydrophobicity and non-selectivity of the photosensitizers, inherent serious hypoxia of tumor tissues and limited penetration depth of light restrict PDT further applications in clinic. Functional polymer nanoparticles can be used as a nanocarrier for accurate PDT. Here, we elucidate the mechanism and application of PDT in cancer treatments, and then review some strategies to administer the biodistribution and activation of photosensitizers (PSs) to ameliorate or utilize the tumor hypoxic microenvironment to enhance the photodynamic therapy effect.
关键词: hypoxia,photodynamic therapy,nanocarriers,photosensitizers
更新于2025-09-04 15:30:14