Smart Theranostic Nanosystems

Mukerji, Ratul; Leong, Kam W.

doi:10.1142/9781783267231_0015

Cited by 3 publications

(4 citation statements)

References 27 publications

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“…Optical therapies usually result in hyperthermia, which is tissue heating within the range of 42−46 °C. According to the literature, irreversible necrosis is achieved by heating at 43 °C for 240 min or at 54 °C for 1 s, 45 which are still far below the melting temperatures (T M ) of any of the proteins involved in this study (T M GFP = 82.0 °C, T M KO = 78.9 °C, T M KR = 84.7 °C).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Interaction of Genetically Encoded Photosensitizers with Scintillating Nanoparticles for X-ray Activated Photodynamic Therapy

Micheletto

Guidelli

Costa-Filho

2021

ACS Appl. Mater. Interfaces

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Photodynamic therapy (PDT) applications are limited by the low penetration of UV−visible light into biological tissues. Considering Xrays as an alternative to excite photosensitizers (PS) in a deeper tumor, an intermediate particle able to convert the X-ray energy into visible light (scintillating nanoparticle, ScNP) is necessary. Moreover, accumulation of PS in the target cells is also required. Genetically encoded proteins could be used as a photosensitizer, allowing the exclusive expression of PS inside the tumor cells. Here, the interaction of eGFP, KillerOrange, and KillerRed proteins with LaF 3 :Tb 3+ ScNP was investigated, for the first time, in terms of its physicochemical and energy transfer properties. The protein structure, stability, and function were evaluated upon adverse physiological conditions and X-ray irradiation. Optimal parameters for energy transfer from ScNP to the proteins were investigated, paving the way for the use of genetically encoded photosensitizers for applications in X-ray activated photodynamic therapy.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Interaction of Genetically Encoded Photosensitizers with Scintillating Nanoparticles for X-ray Activated Photodynamic Therapy

Micheletto

Guidelli

Costa-Filho

2021

ACS Appl. Mater. Interfaces

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“…Mucoadhesion is a property of some natural and synthetic macromolecules that permits them to persist at the site of application and achieve a prolonged action [66]. In this sense, mucoadhesive formulations could bring solutions to posterior segment eye diseases (e.g., diabetic retinopathy and age-related macular degeneration) in which the invasive intravitreal injections are used as the primary route to deliver drugs [10,67]. These types of formulations reduce the precorneal clearance of a drug or bioactive compound while prolonging its residence time.…”

Section: Discussionmentioning

confidence: 99%

Chitosan-Based Nanogels Designed for Betanin-Rich Beetroot Extract Transport: Physicochemical and Biological Aspects

Silva Nieto,

Samaniego López,

Moretton

et al. 2023

Polymers

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Nanotechnology has emerged as a possible solution to improve phytochemicals’ limitations. The objective of the present study was to encapsulate beetroot extract (BR Ext) within a chitosan (CS)-based nanogel (NG) designed via ionic crosslinking with tripolyphosphate (TPP) for betanin (Bet) delivery, mainly in the ophthalmic environment. BR Ext is rich in betanin (Bet) according to thin layer chromatography (TLC), UV-visible spectroscopy, and HPLC analysis. NG presented a monodisperse profile with a size of 166 ± 6 nm and low polydispersity (0.30 ± 0.03). ζ potential (ζ-Pot) of +28 ± 1 is indicative of a colloidally stable system. BR Ext encapsulation efficiency (EE) was 45 ± 3%. TEM, with the respective 3D-surface plots and AFM, showed spherical–elliptical-shaped NG. The BR Ext release profile was biphasic with a burst release followed by slow and sustained phase over 12 h. Mucoadhesion assay demonstrated interactions between NG with mucin. Moreover, NG provided photoprotection and pH stability to BR Ext. FRAP and ABTS assays confirmed that BR Ext maintained antioxidant activity into NG. Furthermore, in vitro assays using human retinal cells displayed absence of cytotoxicity as well as an efficient protection against injury agents (LPS and H2O2). NGs are a promising platform for BR Ext encapsulation, exerting controlled release for ophthalmological use.

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“…Optical therapies usually result in hyperthermia, which is Another situation found during in vivo applications is pH variations. This could be caused by a significant decrease in extracellular and intracellular pH, commonly observed in tumour cells where pH values as low as 5.7 can be found (compared to a pH of 7.4 in normal tissues) 107 . Acidic microenvironments arise in tumours due to their altered vascularization, causing insufficient delivery of metabolites, such as oxygen, to many areas within the tumour.…”

Section: Heterologous Expression and Biophysical Characterizationmentioning

confidence: 99%

“…Hence, there is an increase in lactic acid production under anaerobic conditions and adenosine triphosphate (ATP) hydrolysis, contributing to the increased acidity in tumour microenvironments 107,108 . When subjected to pH variation, proteins can have not only their structure but also their function affected.…”

Section: Heterologous Expression and Biophysical Characterizationmentioning

confidence: 99%

Activation of photosensitive proteins with radioluminescent nanoparticles and X-rays

Micheletto

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Activation of photosensitive proteins with radioluminescent nanoparticles and XraysPhotodynamic therapy (PDT) is traditionally limited due to the poor penetration of ultravioletvisible (UV-vis) light in human tissues. However, advanced technologies allow the excitation of photosensitizers (PS) at different wavelengths, providing opportunities to discover compatible scintillators. A more efficient complex of nanoparticles and photosensitizers can be designed through a further understanding of the properties of each component of the system. This research focuses on the innovative application of X-rays as an alternative to UV-vis light for deeper tumor excitation in PDT.Scintillating nanoparticles (ScNP) are required as intermediates to convert the energy of X-rays into visible light. The role of PS is fulfilled by genetically encoded proteins. We explore the interaction of the eGFP, KillerOrange, and KillerRed proteins with ScNP LaF3:Tb 3+ in terms of their physicochemical properties and energy transfer, while also investigating the structure, stability, and function of such proteins under adverse physiological conditions and X-ray irradiation. In a second system of project interest, we doped Hafnium Oxide (HfO2) nanoparticles with titanium (Ti) to enhance their luminescence properties and created a stable dispersion in PBS buffer. To stabilize the nanoparticles in PBS, we coated them with citric acid (CA). As the PS in this case, we used the miniSOG protein with its C-terminal modified by the insertion of a glutamate (E) sequence, forming miniSOG-PolyE. The proteins exhibited stability under harsh conditions experienced during cancer therapies. Biophysical characterization of the proteins, combined with tests using ionizing radiation, revealed minimal protein interaction with X-rays. We demonstrated the energy transfer from ScNP to eGFP, KO, and KR. The system consisting of eGFP, KO, and KR conjugated to LaF3:Tb 3+ nanoparticles proved efficient in preventing bacterial culture growth, likely through the generation of reactive oxygen species. The genetic modification that resulted in miniSOG-Poly-E increased the binding with the HfO2 nanoparticle and stabilized the colloidal dispersion in environments similar to biological systems. We propose these systems as promising pathways for the use of genetically encoded photosensitizers in PDT applications with X-rays Further research on this topic could pave the way for more effective cancer therapies and shed light on the interaction of scintillating nanoparticles and proteins to create a conjugated nanocomposite with greater dispersion stability in biological media.

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Smart Theranostic Nanosystems

Cited by 3 publications

References 27 publications

Interaction of Genetically Encoded Photosensitizers with Scintillating Nanoparticles for X-ray Activated Photodynamic Therapy

Interaction of Genetically Encoded Photosensitizers with Scintillating Nanoparticles for X-ray Activated Photodynamic Therapy

Chitosan-Based Nanogels Designed for Betanin-Rich Beetroot Extract Transport: Physicochemical and Biological Aspects

Activation of photosensitive proteins with radioluminescent nanoparticles and X-rays

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