scholarly journals In-situ oxygen-generation nanoplatform with dual amplification effect for combined chemo-photodynamic therapy

2021 ◽  
Author(s):  
Qingcheng Song ◽  
Xiangtian Deng ◽  
Wenbo Yang ◽  
Yiran Zhang ◽  
Junyong Li ◽  
...  
Keyword(s):  
Dna Damage ◽  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Therapeutic Effect ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Loading ◽  
Repair Process ◽  
Amplification Effect ◽  
Dual Amplification

Abstract Background Photodynamic therapy (PDT) is a promising method for cancer treatment because of its advantages such as easy operation, good targeting, minimal side effects, low systemic toxicity and less invasiveness. However, the hypoxic microenvironment within the tumor significantly inhibited the therapeutic effect of PDT. The development of targeted nanoplatform for regulating hypoxia microenvironment is an important method to give full play to the therapeutic effect of PDT. Methods In this study, we designed and prepared a novel chemo-photodynamic therapy nanoplatform, which can continuously catalyze the decomposition of H2O2 in tumors to generate oxygen (O2) to enhance the therapeutic effect of PDT, resulting in DNA damage, while releasing MTH1 inhibitors in tumor cells to inhibit the repair process of DNA damage caused by PDT. Results In our work, a simple one-step reduction approach was applied to enable platinum nanoparticles (Pt NPs) growth in situ in the nanochannels of mesoporous silica nanoparticles (MSNs). After physical encapsulation of photosensitizer chlorin e6 (Ce6) and MTH1 inhibitor TH588, the drug loading nanoplatform was modified with an arginine-glycine-aspartic acid (RGD) functionalized liposome shell, resulting in the fabrication of multifunctional nanoplatform MSN-Pt@Ce6/TH588@Liposome-RGD (MPCT@Li-R) with dual amplification effect and achieve the purpose of chemo-photodynamic therapy. Conclusions Our study provides a new strategy for PDT to ablation tumor cells by damaging the DNA of tumor nucleus and mitochondria, meanwhile inhibiting the repair process after the damage.

(S)-Goniothalamin induces DNA damage, apoptosis, and decrease in BIRC5 messenger RNA levels in NCI-H460 cells

2013 ◽  
Vol 33 (1) ◽  
pp. 3-13 ◽  
Author(s):  
SC Semprebon ◽  
 de Fátima ◽  
SR Lepri ◽  
D Sartori ◽  
LR Ribeiro ◽  
...  
Keyword(s):  
Dna Damage ◽  
Tumor Cells ◽  
Messenger Rna ◽  
Dependent Manner ◽  
Apoptosis Induction ◽  
Small Cell Lung ◽  
Concentration Dependent Manner ◽  
H460 Cells ◽  
Rna Levels

(R)-Goniothalamin (R-GNT) is a secondary metabolite isolated from the plants of the genus Goniothalamus. This molecule has attracted the attention of researchers because of its selective cytotoxicity against tumor cells and its ability to induce apoptosis. (S)-Goniothalamin (S-GNT) is a synthetic enantiomer of R-GNT, and its mechanism of action is largely unknown. In this study, we investigated the activity of S-GNT in a human non-small cell lung cancer NCI-H460 cells. We observed that the cells exposed to this compound exhibited cytotoxicity in a concentration-dependent manner. Based on the data obtained through the assessment of apoptosis induction in situ and the comet assay, we suggest that this cytotoxicity occurs due to the potential ability of this molecule to induce DNA damage with the consequent induction of cell death via apoptosis. A significant reduction in the messenger RNA levels of baculoviral inhibitor of apoptosis repeat-containing 5 ( BIRC5) gene that encodes the survivin protein was found. This novel finding may explain the inhibition of cell proliferation and induction of apoptosis in tumor cells caused by this compound.

scholarly journals Hydrophobicity-Tuned Periodic Mesoporous Organo-Silica Nanoparticles for Photodynamic Therapy

2020 ◽  
Vol 21 (7) ◽  
pp. 2586
Author(s):  
Chia-Hui Lin ◽  
Ranjith Kumar Kankala ◽  
Prabhakar Busa ◽  
Chia-Hung Lee
Keyword(s):  
Photodynamic Therapy ◽  
Physicochemical Properties ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Loading ◽  
Membrane Damage ◽  
Protoporphyrin Ix ◽  
Hybrid Nanocomposites ◽  
Cell Membrane Damage

Since their invention, periodic mesoporous organosilicas (PMOs), an innovative class of materials based on organic as well as inorganic hybrid nanocomposites, have gathered enormous interest owing to their advantageous physicochemical attributes over the pristine mesoporous silica nanoparticles (MSNs). To further increase the interactions with the therapeutic guest species and subsequent compatibility as well as the physicochemical properties of PMOs, we demonstrate the post-hydroxylation of benzene-bridged PMO-based nanoparticles for photodynamic therapy (PDT). Initially, the hydrophobic benzene group in the PMO framework is modified through electrophilic substitution-assisted hydroxylation mediated by Fenton as well as Fenton-like reactions utilizing divalent and trivalent metal salts, respectively. These post-grafted PMOs with tuned hydrophobicity resulted in improved biocompatibility as well as drug loading efficiency through governing the interactions in host–guest chemistry by changing the physicochemical properties of the PMO frameworks. Furthermore, the photosensitizer, protoporphyrin IX (PpIX) molecules, encapsulated in the PMO frameworks showed a significant PDT effect in colon carcinoma (HT-29 cell line) and Gram-negative bacterial strain, Escherichia coli (E. coli). Furthermore, the light-induced cytotoxic properties in vitro are confirmed by various tests, including lactate dehydrogenase (LDH) assay for cell membrane damage and caspase assay for apoptosis determination. Indeed, the delivered PpIX molecules from PMOs generated deadly singlet oxygen species intracellularly under visible light irradiation, resulting in cell death through concomitantly triggered apoptotic caspases. Together, our findings demonstrate that this post-modified PMO design is highly advantageous and can be used as an effective PDT platform.

DEVELOPMENT OF A PHOTOSENSITIZER DELIVERY SYSTEM FOR THERAPY AND DIAGNOSTICS IN ONCOLOGY

2020 ◽  
pp. 124-125
Author(s):  
A.Semkina Semkina ◽  
M.Abakumov Abakumov ◽  
P.Ostroverkhov Ostroverkhov ◽  
M. Grin
Keyword(s):  
Photodynamic Therapy ◽  
Physicochemical Properties ◽  
Tumor Cells ◽  
Therapeutic Effect ◽  
Delivery System ◽  
Biological Studies ◽  
Kinetics Of ◽  
Ct26 Tumor

In this work, the MNP-HSA-PEG-PS@4 complex was obtained and its physicochemical properties were studied. Biological studies have also been conducted. Namely, the ability of the drug to accumulate in CT26 tumor cells in vitro and the kinetics of drug accumulation in the tumor in vivo were studied. Then, the effectiveness of photodynamic therapy was studied under different conditions. The maximum therapeutic effect was achieved with irradiation at 1 hour after injection of the drug.

scholarly journals Galactosylated Chitosan-Functionalized Mesoporous Silica Nanoparticle Loading by Calcium Leucovorin for Colon Cancer Cell-Targeted Drug Delivery

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3082 ◽  
Author(s):  
Wei Liu ◽  
Fan Wang ◽  
Yongchao Zhu ◽  
Xue Li ◽  
Xiaojing Liu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Colon Cancer ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Tumor Cells ◽  
Targeted Drug Delivery ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Loading ◽  
Targeted Drug ◽  
Galactosylated Chitosan

Targeted drug delivery to colon cancer cells can significantly improve the efficiency of treatment. We firstly synthesized carboxyl-modified mesoporous silica nanoparticles (MSN–COOH) via two-step synthesis, and then developed calcium leucovorin (LV)-loaded carboxyl-modified mesoporous silica nanoparticles based on galactosylated chitosan (GC), which are galectin receptor-mediated materials for colon-specific drug delivery systems. Both unmodified and functionalized nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), nitrogen sorption, and dynamic light scattering (DLS). Drug release properties and drug loading capacity were determined by ultraviolet spectrophotometry (UV). LV@MSN–COOH/GC had a high LV loading and a drug loading of 18.07%. In vitro, its release, mainly by diffusion, was sustained release. Cell experiments showed that in SW620 cells with the galectin receptor, the LV@MSN–COOH/GC metabolized into methyl tetrahydrofolic acid (MTHF) and 5-fluorouracil (5-FU)@MSN–NH2/GC metabolized into FdUMP in vivo. MTHF and 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) had combined inhibition and significantly downregulated the expression of thymidylate synthase (TS). Fluorescence microscopy and flow cytometry experiments show that MSN–COOH/GC has tumor cell targeting, which specifically recognizes and binds to the galectin receptor in tumor cells. The results show that the nano-dosing system based on GC can increase the concentrations of LV and 5-FU tumor cells and enhance their combined effect against colon cancer.

scholarly journals Can Cerenkov Light Really Induce an Effective Photodynamic Therapy?

Radiation ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 5-17
Author(s):  
Joël Daouk ◽  
Batoul Dhaini ◽  
Jérôme Petit ◽  
Céline Frochot ◽  
Muriel Barberi-Heyob ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Therapeutic Effect ◽  
Radioactive Isotopes ◽  
Major Drawback ◽  
Equation Resolution ◽  
Original Works ◽  
Uv Photons ◽  
Cerenkov Light

Photodynamic therapy (PDT) is a promising therapeutic strategy for cancers where surgery and radiotherapy cannot be effective. PDT relies on the photoactivation of photosensitizers, most of the time by lasers to produced reactive oxygen species and notably singlet oxygen. The major drawback of this strategy is the weak light penetration in the tissues. To overcome this issue, recent studies proposed to generate visible light in situ with radioactive isotopes emitting charged particles able to produce Cerenkov radiation. In vitro and preclinical results are appealing, but the existence of a true, lethal phototherapeutic effect is still controversial. In this article, we have reviewed previous original works dealing with Cerenkov-induced PDT (CR-PDT). Moreover, we propose a simple analytical equation resolution to demonstrate that Cerenkov light can potentially generate a photo-therapeutic effect, although most of the Cerenkov photons are emitted in the UV-B and UV-C domains. We suggest that CR-PDT and direct UV-tissue interaction act synergistically to yield the therapeutic effect observed in the literature. Moreover, adding a nanoscintillator in the photosensitizer vicinity would increase the PDT efficacy, as it will convert Cerenkov UV photons to light absorbed by the photosensitizer.

Critical Periods during the in Situ Repair of Radiation-Induced DNA Damage in Rat Cerebellar Neurons and 9L Brain Tumor Cells

1982 ◽  
Vol 90 (3) ◽  
pp. 479 ◽  
Author(s):  
James V. Wierowski ◽  
Rolland R. Thomas ◽  
Paul Ritter ◽  
Kenneth T. Wheeler
Keyword(s):  
Dna Damage ◽  
Brain Tumor ◽  
Tumor Cells ◽  
Critical Periods ◽  
Cerebellar Neurons ◽  
Brain Tumor Cells ◽  
Radiation Induced ◽  
In Situ Repair

Novel TiO2/PEGDA Hybrid Hydrogel Prepared in Situ on Tumor Cells for Effective Photodynamic Therapy

2013 ◽  
Vol 5 (23) ◽  
pp. 12317-12322 ◽  
Author(s):  
Hui Zhang ◽  
Ronghua Shi ◽  
Anjian Xie ◽  
Juchuan Li ◽  
Long Chen ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Hybrid Hydrogel

Novel Formulation Development and Evaluation of Nanoparticles Based in Situ Gelling System for The Ophthalmic Delivery of Ciprofloxacin Hydrochloride

2015 ◽  
Vol 5 (4) ◽  
Author(s):  
Kranti Singh ◽  
Surajpal Verma ◽  
Shyam Prasad ◽  
Indu Bala
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Drug Loading ◽  
In Vitro Release ◽  
Formulation Development ◽  
Ciprofloxacin Hydrochloride ◽  
Potential Value ◽  
The Mean ◽  
In Situ Gelling

Ciprofloxacin hydrochloride loaded Eudragit RS100 nanoparticles were prepared by using w/o/w emulsification (multiple emulsification) solvent evaporation followed by drying of nanoparticles at 50°C. The nanoparticles were further incorporated into the pH-triggered in situ gel forming system which was prepared using Carbopol 940 in combination with HPMC as viscosifying agent. The developed nanoparticles was evaluated for particle size, zeta potential value and loading efficiency; nanoparticle incorporated in situ gelling system was evaluated for pH, clarity, gelling strength, rheological studies, in-vitro release studies and ex-vivo precorneal permeation studies. The nanopaticle showed the mean particle size varying between 263.5nm - 325.9 nm with the mean zeta potential value of -5.91 mV to -8.13 mV and drug loading capacity varied individually between 72.50% to 98.70% w/w. The formulation was clear with no suspended particles, showed good gelling properties. The gelling was quick and remained for longer time period. The developed formulation was therapeutically efficacious, stable and non-irritant. It provided the sustained release of drug over a period of 8-10 hours.

Optical Properties of Photodynamic Therapy Drugs in Different Environments: The Paradigmatic Case of Temoporfin

2020 ◽  
Author(s):  
busenur Aslanoglu ◽  
Ilya Yakavets ◽  
Vladimir Zorin ◽  
Henri-Pierre Lassalle ◽  
Francesca Ingrosso ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Optical Properties ◽  
Photodynamic Therapy ◽  
Minimally Invasive ◽  
Visible Light ◽  
Cancer Treatment ◽  
Singlet Oxygen ◽  
Tumor Cells ◽  
Molecular Oxygen ◽  
Computational Tools

Computational tools have been used to study the photophysical and photochemical features of photosensitizers in photodynamic therapy (PDT) –a minimally invasive, less aggressive alternative for cancer treatment. PDT is mainly based by the activation of molecular oxygen through the action of a photoexcited sensitizer (photosensitizer). Temoporfin, widely known as mTHPC, is a second-generation photosensitizer, which produces the cytotoxic singlet oxygen when irradiated with visible light and hence destroys tumor cells. However, the bioavailability of the mostly hydrophobic photosensitizer, and hence its incorporation into the cells, is fundamental to achieve the desired effect on malignant tissues by PDT. In this study, we focus on the optical properties of the temoporfin chromophore in different environments –in <i>vacuo</i>, in solution, encapsulated in drug delivery agents, namely cyclodextrin, and interacting with a lipid bilayer.

Enhanced drug loading of in situ forming gels for oral mucositis pain control

2021 ◽  
Vol 595 ◽  
pp. 120225
Author(s):  
Tingting Li ◽  
Rajesh V. Lalla ◽  
Diane J. Burgess
Keyword(s):  
Oral Mucositis ◽  
Pain Control ◽  
Drug Loading ◽  
In Situ Forming
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