scholarly journals An amphiphilic dendrimer as a light-activable immunological adjuvant for in situ cancer vaccination

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yongchao Wang ◽  
Ningqiang Gong ◽  
Chi Ma ◽  
Yuxuan Zhang ◽  
Hong Tan ◽  
...  

AbstractImmunological adjuvants are essential for successful cancer vaccination. However, traditional adjuvants have some limitations, such as lack of controllability and induction of systemic toxicity, which restrict their broad application. Here, we present a light-activable immunological adjuvant (LIA), which is composed of a hypoxia-responsive amphiphilic dendrimer nanoparticle loaded with chlorin e6. Under irradiation with near-infrared light, the LIA not only induces tumour cell lysis and tumour antigen release, but also promotes the structural transformation of 2-nitroimidazole containing dendrimer to 2-aminoimidazole containing dendrimer which can activate dendritic cells via the Toll-like receptor 7-mediated signaling pathway. The LIA efficiently inhibits both primary and abscopal tumour growth and induces strong antigen-specific immune memory effect to prevent tumour metastasis and recurrence in vivo. Furthermore, LIA localizes the immunological adjuvant effect at the tumour site. We demonstrate this light-activable immunological adjuvant offers a safe and potent platform for in situ cancer vaccination.

Nanoscale ◽  
2020 ◽  
Vol 12 (18) ◽  
pp. 10361-10368
Author(s):  
Yunxia Wu ◽  
Judun Zheng ◽  
Da Xing ◽  
Tao Zhang

Spatiotemporally controllable platform enables in situ fluorogenic labeling of alkene sialic acids based upconverting photoclick nanoprobe.


2020 ◽  
Vol 48 (6) ◽  
pp. 2657-2667
Author(s):  
Felipe Montecinos-Franjola ◽  
John Y. Lin ◽  
Erik A. Rodriguez

Noninvasive fluorescent imaging requires far-red and near-infrared fluorescent proteins for deeper imaging. Near-infrared light penetrates biological tissue with blood vessels due to low absorbance, scattering, and reflection of light and has a greater signal-to-noise due to less autofluorescence. Far-red and near-infrared fluorescent proteins absorb light >600 nm to expand the color palette for imaging multiple biosensors and noninvasive in vivo imaging. The ideal fluorescent proteins are bright, photobleach minimally, express well in the desired cells, do not oligomerize, and generate or incorporate exogenous fluorophores efficiently. Coral-derived red fluorescent proteins require oxygen for fluorophore formation and release two hydrogen peroxide molecules. New fluorescent proteins based on phytochrome and phycobiliproteins use biliverdin IXα as fluorophores, do not require oxygen for maturation to image anaerobic organisms and tumor core, and do not generate hydrogen peroxide. The small Ultra-Red Fluorescent Protein (smURFP) was evolved from a cyanobacterial phycobiliprotein to covalently attach biliverdin as an exogenous fluorophore. The small Ultra-Red Fluorescent Protein is biophysically as bright as the enhanced green fluorescent protein, is exceptionally photostable, used for biosensor development, and visible in living mice. Novel applications of smURFP include in vitro protein diagnostics with attomolar (10−18 M) sensitivity, encapsulation in viral particles, and fluorescent protein nanoparticles. However, the availability of biliverdin limits the fluorescence of biliverdin-attaching fluorescent proteins; hence, extra biliverdin is needed to enhance brightness. New methods for improved biliverdin bioavailability are necessary to develop improved bright far-red and near-infrared fluorescent proteins for noninvasive imaging in vivo.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Songtao Zhang ◽  
Longhai Jin ◽  
Jianhua Liu ◽  
Yang Liu ◽  
Tianqi Zhang ◽  
...  

AbstractIn spite of the tumor microenvironments responsive cancer therapy based on Fenton reaction (i.e., chemodynamic therapy, CDT) has been attracted more attentions in recent years, the limited Fenton reaction efficiency is the important obstacle to further application in clinic. Herein, we synthesized novel FeO/MoS2 nanocomposites modified by bovine serum albumin (FeO/MoS2-BSA) with boosted Fenton reaction efficiency by the synergistic effect of co-catalyze and photothermal effect of MoS2 nanosheets triggered by the second near-infrared (NIR II) light. In the tumor microenvironments, the MoS2 nanosheets not only can accelerate the conversion of Fe3+ ions to Fe2+ ions by Mo4+ ions on their surface to improve Fenton reaction efficiency, but also endow FeO/MoS2-BSA with good photothermal performances for photothermal-enhanced CDT and photothermal therapy (PTT). Consequently, benefiting from the synergetic-enhanced CDT/PTT, the tumors are eradicated completely in vivo. This work provides innovative synergistic strategy for constructing nanocomposites for highly efficient CDT.


Small ◽  
2008 ◽  
Vol 4 (7) ◽  
pp. 1001-1007 ◽  
Author(s):  
Takuro Niidome ◽  
Yasuyuki Akiyama ◽  
Kohei Shimoda ◽  
Takahito Kawano ◽  
Takeshi Mori ◽  
...  

Nanomaterials ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 582 ◽  
Author(s):  
Álvaro Cárcamo-Martínez ◽  
Juan Domínguez-Robles ◽  
Brónach Mallon ◽  
Md. Taifur Raman ◽  
Ana Sara Cordeiro ◽  
...  

Current strategies for the treatment of superficial non-melanoma skin cancer (NMSC) lesions include topical imoquimod, 5-fluorouracil, and photodynamic therapy. Although these treatments are effective, burning pain, blistering, and dermatitis have been reported as frequent side effects, making these therapies far from ideal. Plasmonic materials have been investigated for the induction of hyperthermia and use in cancer treatment. In this sense, the effectiveness of intratumorally and systemically injected gold nanorods (GnRs) in inducing cancer cell death upon near-infrared light irradiation has been confirmed. However, the in vivo long-term toxicity of these particles has not yet been fully documented. In the present manuscript, GnRs were included in a crosslinked polymeric film, evaluating their mechanical, swelling, and adhesion properties; moreover, their ability to heat up neonatal porcine skin (such as a skin model) upon irradiation was tested. Inclusion of GnRs into the films did not affect mechanical or swelling properties. GnRs were not released after film swelling, as they remained entrapped in the polymeric network; moreover, films did not adhere to porcine skin, altogether showing the enhanced biocompatibility of the material. GnR-loaded films were able to heat up the skin model over 40 °C, confirming the potential of this system for non-invasive local hyperthermia applications.


Biosensors ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 174
Author(s):  
Ramzan Ullah ◽  
Karl Doerfer ◽  
Pawjai Khampang ◽  
Faraneh Fathi ◽  
Wenzhou Hong ◽  
...  

Proper ventilation of a patient with an endotracheal tube (ETT) requires proper placement of the ETT. We present a sensitive, noninvasive, operator-free, and cost-effective optical sensor, called Opt-ETT, for the real-time assessment of ETT placement and alerting of the clinical care team should the ETT become displaced. The Opt-ETT uses a side-firing optical fiber, a near-infrared light-emitting diode, two photodetectors with an integrated amplifier, an Arduino board, and a computer loaded with a custom LabVIEW program to monitor the position of the endotracheal tube inside the windpipe. The Opt-ETT generates a visual and audible warning if the tube moves over a distance set by the operator. Displacement prediction is made using a second-order polynomial fit to the voltages measured from each detector. The system is tested on ex vivo porcine tissues, and the accuracy is determined to be better than 1.0 mm. In vivo experiments with a pig are conducted to test the performance and usability of the system.


Nanomaterials ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 91 ◽  
Author(s):  
Chuan Zhang ◽  
Yuzhuo Wang ◽  
Yue Zhao ◽  
Hou Liu ◽  
Yueqi Zhao ◽  
...  

The chemotherapy of stimuli-responsive drug delivery systems (SDDSs) is a promising method to enhance cancer treatment effects. However, the low efficiency of chemotherapy drugs and poor degradation partly limit the application of SDDSs. Herein, we report doxorubicin (DOX)-loading mixed micelles for biotin-targeting drug delivery and enhanced photothermal/photodynamic therapy (PTT/PDT). Glutathione (GSH)-responsive mixed micelles were prepared by a dialysis method, proportionally mixing polycaprolactone-disulfide bond-biodegradable photoluminescent polymer (PCL-SS-BPLP) and biotin-polyethylene glycol-cypate (biotin-PEG-cypate). Chemically linking cypate into the mixed micelles greatly improved cypate solubility and PTT/PDT effect. The micelles also exhibited good monodispersity and stability in cell medium (~119.7 nm), low critical micelles concentration, good biodegradation, and photodecomposition. The high concentration of GSH in cancer cells and near-infrared light (NIR)-mediated cypate decomposition were able to achieve DOX centralized release. Meanwhile, the DOX-based chemotherapy combined with cypate-based NIR-triggered hyperthermia and reactive oxygen species could synergistically induce HepG2 cell death and apoptosis. The in vivo experiments confirmed that the micelles generated hyperthermia and achieved a desirable therapeutic effect. Therefore, the designed biodegradable micelles are promising safe nanovehicles for antitumor drug delivery and chemo/PTT/PDT combination therapy.


2019 ◽  
Vol 116 (41) ◽  
pp. 20296-20302 ◽  
Author(s):  
Zhixuan Zhou ◽  
Jiangping Liu ◽  
Juanjuan Huang ◽  
Thomas W. Rees ◽  
Yiliang Wang ◽  
...  

Photodynamic therapy (PDT) is a treatment procedure that relies on cytotoxic reactive oxygen species (ROS) generated by the light activation of a photosensitizer. The photophysical and biological properties of photosensitizers are vital for the therapeutic outcome of PDT. In this work a 2D rhomboidal metallacycle and a 3D octahedral metallacage were designed and synthesized via the coordination-driven self-assembly of a Ru(II)-based photosensitizer and complementary Pt(II)-based building blocks. The metallacage showed deep-red luminescence, a large 2-photon absorption cross-section, and highly efficient ROS generation. The metallacage was encapsulated into an amphiphilic block copolymer to form nanoparticles to encourage cell uptake and localization. Upon internalization into cells, the nanoparticles selectively accumulate in the lysosomes, a favorable location for PDT. The nanoparticles are almost nontoxic in the dark, and can efficiently destroy tumor cells via the generation of ROS in the lysosomes under 2-photon near-infrared light irradiation. The superb PDT efficacy of the metallacage-containing nanoparticles was further validated by studies on 3D multicellular spheroids (MCS) and in vivo studies on A549 tumor-bearing mice.


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