scholarly journals An Injectable Hydrogel for Enhanced FeGA-Based Chemodynamic Therapy by Increasing Intracellular Acidity

2021 ◽  
Vol 11 ◽  
Author(s):  
Wen Zeng ◽  
Dazhen Jiang ◽  
Zeming Liu ◽  
Weilong Suo ◽  
Ziqi Wang ◽  
...  
Keyword(s):  
Near Infrared ◽  
Monocarboxylic Acid ◽  
Tumor Therapy ◽  
Hydroxycinnamic Acid ◽  
Tumor Treatment ◽  
Injectable Hydrogel ◽  
Acid Deficiency ◽  
Monocarboxylic Acid Transporter

Hydroxyl radical (•OH)-mediated chemodynamic therapy (CDT) is an emerging antitumor strategy, however, acid deficiency in the tumor microenvironment (TME) hampers its efficacy. In this study, a new injectable hydrogel was developed as an acid-enhanced CDT system (AES) for improving tumor therapy. The AES contains iron–gallic acid nanoparticles (FeGA) and α-cyano-4-hydroxycinnamic acid (α-CHCA). FeGA converts near-infrared laser into heat, which results in agarose degradation and consequent α-CHCA release. Then, as a monocarboxylic acid transporter inhibitor, α-CHCA can raise the acidity in TME, thus contributing to an increase in ·OH-production in FeGA-based CDT. This approach was found effective for killing tumor cells both in vitro and in vivo, demonstrating good therapeutic efficacy. In vivo investigations also revealed that AES had outstanding biocompatibility and stability. This is the first study to improve FeGA-based CDT by increasing intracellular acidity. The AES system developed here opens new opportunities for effective tumor treatment.

scholarly journals Hyaluronic acid modified covalent organic polymers for efficient targeted and oxygen-evolved phototherapy

2020 ◽  
Author(s):  
Fangpeng Shu ◽  
Taowei Yang ◽  
Xuefeng Zhang ◽  
Wenbin Chen ◽  
Kaihui Wu ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Colloidal Stability ◽  
Near Infrared ◽  
Combined Therapy ◽  
Tumor Therapy ◽  
Photothermal Effect ◽  
Organic Polymers ◽  
New Paradigm

Abstract The integration of multiple functions with organic polymers-based nanoagent holds great potential to potentiate its therapeutic efficacy, but still remains challenges. In the present study, we design and prepare an organic nanoagent with oxygen-evolved and targeted ability for improved phototherapeutic efficacy. The iron ions doped poly diaminopyridine (FeD) is prepared by oxidize polymerization and modified with hyaluronic acid (HA). The obtained FeDH appears uniform morphology and size. Its excellent colloidal stability and biocompatibility are demonstrated. Specifically, the FeDH exhibits catalase-like activity in the presence of hydrogen peroxide. After loading of photosensitizer indocyanine green (ICG), the ICG@FeDH not only demonstrates favorable photothermal effect, but also shows improved generation ability of reactive oxygen species (ROS) under near-infrared laser irradiation. Moreover, the targeted uptake of ICG@FeDH in tumor cells is directly observed. As consequence, the superior phototherapeutic efficacy of the targeted ICG@FeDH over non-targeted counterparts is also confirmed in vitro and in vivo. Hence, the results demonstrate that the developed nanoagent rationally integrates the targeted ability, oxygen-evolved capacity and combined therapy in one system, offering a new paradigm of polymer-based nanomedicine for tumor therapy.

scholarly journals Assessment of the Theranostic Potential of Gold Nanostars—A Multimodal Imaging and Photothermal Treatment Study

Nanomaterials ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2112 ◽  
Author(s):  
Antoine D’Hollander ◽  
Greetje Vande Velde ◽  
Hilde Jans ◽  
Bram Vanspauwen ◽  
Elien Vermeersch ◽  
...  
Keyword(s):  
Near Infrared ◽  
Tumor Imaging ◽  
Photoacoustic Imaging ◽  
Tumor Therapy ◽  
Infrared Region ◽  
Tumor Cell Death ◽  
Gold Nanostars ◽  
Theranostic Agents

Gold nanoparticles offer the possibility to combine both imaging and therapy of otherwise difficult to treat tumors. To validate and further improve their potential, we describe the use of gold nanostars that were functionalized with a polyethyleneglycol-maleimide coating for in vitro and in vivo photoacoustic imaging (PAI), computed tomography (CT), as well as photothermal therapy (PTT) of cancer cells and tumor masses, respectively. Nanostar shaped particles show a high absorption coefficient in the near infrared region and have a hydrodynamic size in biological medium around 100 nm, which allows optimal intra-tumoral retention. Using these nanostars for in vitro labeling of tumor cells, high intracellular nanostar concentrations could be achieved, resulting in high PAI and CT contrast and effective PTT. By injecting the nanostars intratumorally, high contrast could be generated in vivo using PAI and CT, which allowed successful multi-modal tumor imaging. PTT was successfully induced, resulting in tumor cell death and subsequent inhibition of tumor growth. Therefore, gold nanostars are versatile theranostic agents for tumor therapy.

scholarly journals Deep-Tissue Photothermal Therapy Using Laser Illumination at NIR-IIa Window

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Xunzhi Wu ◽  
Yongkuan Suo ◽  
Hui Shi ◽  
Ruiqi Liu ◽  
Fengxia Wu ◽  
...  
Keyword(s):  
Photothermal Therapy ◽  
Near Infrared ◽  
Laser Excitation ◽  
Tumor Treatment ◽  
Deep Tissue ◽  
Laser Illumination ◽  
Nir Light ◽  
Cell Ablation

Abstract Photothermal therapy (PTT) using near-infrared (NIR) light for tumor treatment has triggered extensive attentions because of its advantages of noninvasion and convenience. The current research on PTT usually uses lasers in the first NIR window (NIR-I; 700–900 nm) as irradiation source. However, the second NIR window (NIR-II; 1000–1700 nm) especially NIR-IIa window (1300–1400 nm) is considered much more promising in diagnosis and treatment as its superiority in penetration depth and maximum permissible exposure over NIR-I window. Hereby, we propose the use of laser excitation at 1275 nm, which is approved by Food and Drug Administration for physical therapy, as an attractive technique for PTT to balance of tissue absorption and scattering with water absorption. Specifically, CuS-PEG nanoparticles with similar absorption values at 1275 and 808 nm, a conventional NIR-I window for PTT, were synthesized as PTT agents and a comparison platform, to explore the potential of 1275 and 808 nm lasers for PTT, especially in deep-tissue settings. The results showed that 1275 nm laser was practicable in PTT. It exhibited much more desirable outcomes in cell ablation in vitro and deep-tissue antitumor capabilities in vivo compared to that of 808 nm laser. NIR-IIa laser illumination is superior to NIR-I laser for deep-tissue PTT, and shows high potential to improve the PTT outcome.

scholarly journals Sequential Drug Delivery By Injectable Macroporous Hydrogels For Combined Photodynamic-Chemotherapy

2021 ◽  
Author(s):  
Yuanyuan Zhong ◽  
Li Zhang ◽  
Shian Sun ◽  
Zhenghao Zhou ◽  
Yunsu Ma ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Near Infrared ◽  
Early Stage ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Sequential Release ◽  
Therapy Effect ◽  
Hollow Mesoporous Silica

Abstract With hollow mesoporous silica (hMSN) and injectable macroporous hydrogel (Gel) used as the internal and external drug-loading material respectively, a sequential drug delivery system DOX-CA4P@Gel was constructed, in which combretastatin A4 phosphate (CA4P) and doxorubicin (DOX) were both loaded. The anti-angiogenic drug, CA4P was initially released due to the degradation of Gel, followed by the anti-cell proliferative drug, DOX, released from hMSN in tumor microenvironment. Results showed that CA4P was mainly released at the early stage. At 48 h, CA4P release reached 71.08%, while DOX was only 14.39%. At 144 h, CA4P was 78.20%, while DOX release significantly increased to 61.60%, showing an obvious sequential release behavior. Photodynamic properties of porphyrin endow hydrogel (φΔ(Gel)=0.91) with enhanced tumor therapy effect. In vitro and in vivo experiments showed that dual drugs treated groups have better tumor inhibition than solo drug under near infrared laser irradiation, indicating the effectivity of combined photodynamic-chemotherapy.

scholarly journals Injectable Hydrogel for Synergetic Low Dose Radiotherapy, Chemodynamic Therapy and Photothermal Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Mingzhu Chen ◽  
Ziqi Wang ◽  
Weilong Suo ◽  
Zhirong Bao ◽  
Hong Quan
Keyword(s):  
Photothermal Therapy ◽  
Low Dose ◽  
Tumor Therapy ◽  
Intratumoral Injection ◽  
Low Dose Radiation ◽  
Injectable Hydrogel ◽  
Low Dose Radiotherapy ◽  
Dose Radiation

Higher doses of radiotherapy (RT) are associated with resistance induction, therefore highly selective and controllable radiosensitizers are urgently needed. To address this issue, we developed a FeGA-based injectable hydrogel system (FH) that can be used in combination with low-dose radiation. Our FH can deliver FeGA directly to the tumor site via intratumoral injection, where it is a reservoir-based system to conserve FeGA. The photothermal properties of FeGA steadily dissolve FH under laser irradiation, and, simultaneously, FeGA reacts with a large amount of H2O2 in the cell to produce OH (Fenton reaction) which is highly toxic to mitochondria, rendering the cell inactive and reducing radiotherapy resistance. In vivo and in vitro studies suggest that combining the FH and NIR irradiation with RT (2Gy) can significantly reduce tumor proliferation without side effects such as inflammation. To conclude, this is the first study to achieve combined chemodynamic therapy (CDT) and photothermal therapy (PTT) in situ treatment, and the best therapeutic effect can be obtained with a low-dose radiation combination, thus expanding the prospects of FeGA-based tumor therapy.

scholarly journals Hyaluronic acid modified covalent organic polymers for efficient targeted and oxygen-evolved phototherapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fangpeng Shu ◽  
Taowei Yang ◽  
Xuefeng Zhang ◽  
Wenbin Chen ◽  
Kaihui Wu ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Colloidal Stability ◽  
Near Infrared ◽  
Combined Therapy ◽  
Tumor Therapy ◽  
Photothermal Effect ◽  
Organic Polymers ◽  
New Paradigm

AbstractThe integration of multiple functions with organic polymers-based nanoagent holds great potential to potentiate its therapeutic efficacy, but still remains challenges. In the present study, we design and prepare an organic nanoagent with oxygen-evolved and targeted ability for improved phototherapeutic efficacy. The iron ions doped poly diaminopyridine (FeD) is prepared by oxidize polymerization and modified with hyaluronic acid (HA). The obtained FeDH appears uniform morphology and size. Its excellent colloidal stability and biocompatibility are demonstrated. Specifically, the FeDH exhibits catalase-like activity in the presence of hydrogen peroxide. After loading of photosensitizer indocyanine green (ICG), the ICG@FeDH not only demonstrates favorable photothermal effect, but also shows improved generation ability of reactive oxygen species (ROS) under near-infrared laser irradiation. Moreover, the targeted uptake of ICG@FeDH in tumor cells is directly observed. As consequence, the superior phototherapeutic efficacy of the targeted ICG@FeDH over non-targeted counterparts is also confirmed in vitro and in vivo. Hence, the results demonstrate that the developed nanoagent rationally integrates the targeted ability, oxygen-evolved capacity and combined therapy in one system, offering a new paradigm of polymer-based nanomedicine for tumor therapy.

Hollow NiAl(OH)x Nanocapsules to Enable Effective Glucose Oxidase Delivery and Synergistic Therapy

2020 ◽  
Vol 16 (5) ◽  
pp. 640-651
Author(s):  
Bin Liu ◽  
Qiang Chu ◽  
Linhua Liao ◽  
Yongjun Wu ◽  
Lucy Di Silvio ◽  
...  
Keyword(s):  
Glucose Oxidase ◽  
Tumor Therapy ◽  
Reaction Products ◽  
Tumor Treatment ◽  
Intrinsic Degradation ◽  
Degradation Properties ◽  
First Time ◽  
Intracellular Glucose

Cellular starvation induced by glucose oxidase (GOx) had been extensively explored as a potential approach for tumor therapy. However, the therapeutic efficacy suffers daunting challenges due to the unsatisfactory intracellular transportation of GOx molecules. Herein for the first time, hydroxide nanoparticles with unique hollow microstructure (denoted as H-NiAl(OH)x) were designed and synthesized for GOx delivery. In this system, despite its intrinsic degradation properties in acidic tumor microenvironment, Ni2+ ions released during degradation may catalyze a Fenton reaction to induce considerable production of cytotoxic hydroxyl radicals (OH). The cavity of hollow nanocapsules provides large surface area, and favors GOx capsulation and delivery. The findings indicate the intracellular glucose can be effectively consumed by GOx transported, and the reaction products consisting of acid and H2O2 facilitate the OH induction of nanocapsules in a synergistic manner. Both in vitro and in vivo antitumor properties have been consequently achieved by H-NiAl(OH)x/GOx systems. This study offering catalytic nanocapsules based on Ni2+ ions may spark a series of follow-on explorations in constructing drug delivery and therapeutic systems for synergistic tumor treatment.

scholarly journals Hyaluronic Acid Modified Covalent Organic Polymers for Efficient Targeted and Oxygen-Evolved Phototherapy

2020 ◽  
Author(s):  
Fangpeng Shu ◽  
Taowei Yang ◽  
Xuefeng Zhang ◽  
Wenbin Chen ◽  
Kaihui Wu ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Colloidal Stability ◽  
Near Infrared ◽  
Combined Therapy ◽  
Tumor Therapy ◽  
Photothermal Effect ◽  
Organic Polymers ◽  
New Paradigm

Abstract The integration of multiple functions with organic polymers-based nanoagent holds great potential to potentiate its therapeutic efficacy, but still remains challenges. In the present study, we design and prepare an organic nanoagent with oxygen-evolved and targeted ability for improved phototherapeutic efficacy. The iron ions doped poly diaminopyridine (FeD) is prepared by oxidize polymerization and modified with hyaluronic acid (HA). The obtained FeDH appears uniform morphology and size. Its excellent colloidal stability and biocompatibility are demonstrated. Specifically, the FeDH exhibits catalase-like activity in the presence of hydrogen peroxide. After loading of photosensitizer indocyanine green (ICG), the ICG@FeDH not only demonstrates favorable photothermal effect, but also shows improved generation ability of reactive oxygen species (ROS) under near-infrared laser irradiation. Moreover, the targeted uptake of ICG@FeDH in tumor cells is directly observed. As consequence, the superior phototherapeutic efficacy of the targeted ICG@FeDH over non-targeted counterparts is also confirmed in vitro and in vivo. Hence, the results demonstrate that the developed nanoagent rationally integrates the targeted ability, oxygen-evolved capacity and combined therapy in one system, offering a new paradigm of polymer-based nanomedicine for tumor therapy.

scholarly journals Irradiation pretreatment enhances the therapeutic efficacy of platelet-membrane-camouflaged antitumor nanoparticles

2020 ◽  
Author(s):  
Yin Chen ◽  
Xue Shen ◽  
Songling Han ◽  
Tao Wang ◽  
Jianqi Zhao ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Near Infrared ◽  
Antitumor Agents ◽  
Tumor Therapy ◽  
Platelet Membrane ◽  
Antitumor Action ◽  
X Ray ◽  
4T1 Breast Cancer

Abstract Backgroud: Cell membrane-based nanocarriers are promising candidates for delivering antitumor agents. The employment of a simple and feasible method to improve the tumor-targeting abilities of these systems is appealing for further application. Herein, we prepared a platelet membrane (PM)-camouflaged antitumor nanoparticle. The effects of irradiation pretreatment on tumor targeting of the nanomaterial and on its antitumor action were evaluated. Results: The biomimetic nanomaterial constructed by indocyanine green, poly(d,l-lactide-co-glycolide), and PM is termed PINPs@PM. A 4-Gy X-ray irradiation increased the proportions of G2/M phase and Caveolin-1 content in 4T1 breast cancer cells, contributing to an endocytic enhancement of PINPs@PM. PINPs@PM produced hyperthermia and reactive oxygen species upon excitation by near-infrared irradiation, which were detrimental to the cytoplasmic lysosome and resulted in cell death. Irradiation pretreatment thus strengthened the antitumor activity of PINPs@PM in vitro. Mice experiments revealed that irradiation enhanced the tumor targeting capability of PINPs@PM in vivo. When the same dose of PINPs@PM was intravenously administered, irradiated mice had a better outcome than did mice without X-ray pretreatment. Conclusion: The study demonstrates an effective strategy combining irradiation pretreatment and PM camouflage to deliver antitumor nanoparticles, which may be instrumental for targeted tumor therapy.

scholarly journals Irradiation pretreatment enhances the therapeutic efficacy of platelet-membrane- camouflaged antitumor nanoparticles

2019 ◽  
Author(s):  
Yin Chen ◽  
Xue Shen ◽  
Songling Han ◽  
Tao Wang ◽  
Jianqi Zhao ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Near Infrared ◽  
Antitumor Agents ◽  
Tumor Therapy ◽  
Platelet Membrane ◽  
Antitumor Action ◽  
X Ray ◽  
4T1 Breast Cancer

Abstract Backgroud: Cell membrane-based nanocarriers are promising candidates for delivering antitumor agents. The employment of a simple and feasible method to improve the tumor-targeting abilities of these systems is appealing for further application. Herein, we prepared a platelet membrane (PM)-camouflaged antitumor nanoparticle. The effects of irradiation pretreatment on tumor targeting of the nanomaterial and on its antitumor action were evaluated.Results: The biomimetic nanomaterial constructed by indocyanine green, poly(d,l-lactide-co-glycolide), and PM is termed PINPs@PM. A 4-Gy X-ray irradiation enabled the endocytic enhancement of PINPs@PM by 4T1 breast cancer cells. PINPs@PM produced hyperthermia and reactive oxygen species upon excitation by near-infrared irradiation, which were detrimental to the cytoplasmic lysosome and resulted in cell death. Irradiation pretreatment thus strengthened the antitumor activity of PINPs@PM in vitro. Mice experiments revealed that irradiation enhanced the tumor targeting capability of PINPs@PM in vivo. When the same dose of PINPs@PM was intravenously administered, irradiated mice had a better outcome than did mice without X-ray pretreatment. Conclusion: The study demonstrates an effective strategy combining irradiation pretreatment and PM camouflage to deliver antitumor nanoparticles, which may be instrumental for targeted tumor therapy.

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