digital-planimetry-for-assessing-wound-closure-kinetics-mouse

Digital Planimetry for Assessing Wound Closure Kinetics in a Mouse Model

Chronic wounds, due to their high prevalence, are a serious global health concern. Effective therapeutic strategies can significantly accelerate healing, ...

National Institute for Nuclear Research

Among the nanomaterials, rare sesquioxides (lanthanide oxides such as LuO) are of interest due to their adequate thermal conductivity, excellent chemical stability, and high light output. The prostate-specific membrane antigen (PSMA) is an integral multifunctional protein overexpressed in various types of cancer cells. The radiolabeled PSMA inhibitor peptides (iPSMA) have demonstrated their usefulness as specific probes in the treatment and detection of a wide variety of neoplasms, mainly due to their high in vivo recognition by the PSMA protein. The objective of this research was to synthesize LuO-iPSMA nanoparticles (NPs) and characterize their physicochemical properties before and after neutron activation, as well as to assess their biodistribution profile and in vitro potential to target cells overexpressing PSMA. The LuO NPs were synthesized by the precipitation-calcination method and conjugated to the iPSMA peptide using DOTA (1,4,7,10-tetraazocyclodecane-N,N',N″,N‴-tetraacetic acid) as a linking agent. Results of the physicochemical characterization by FT-IR and UV-Vis spectroscopies, SEM, TEM, DLS, HRTEM, SAED, DSC-TGA, and X-ray diffraction indicated the formation of LuO-iPSMA NPs (diameter of 29.98 ± 9.07 nm), which were not affected in their physicochemical properties after neutron activation. LuO-iPSMA NPs showed high affinity (K = 5.7 ± 1.9 nM) for the PSMA protein, evaluated by the saturation assay on HepG2 hepatocellular carcinoma cells (PSMA-positive). The biodistribution profile of the nanosystem in healthy mice showed the main uptake in the liver. After irradiation, radioactive LuO-iPSMA NPs exhibited radioluminescent properties, making the in vivo acquisition of their biodistribution, via optical imaging, possible. The results obtained from this research validate the execution of additional preclinical studies with the objective of evaluating the potential of the LuO-iPSMA NPs for the targeted radiotherapy and in vivo imaging of tumors overexpressing the PSMA protein.

Synthesis, chemical and biochemical characterization of LuO-iPSMA nanoparticles activated by neutron irradiation.

Reconstituted high-density lipoprotein (rHDL) nanoparticles are excellent transporters of molecules and very useful for targeted therapy as they specifically recognize the scavenger receptor, class B1 (SR-B1) that is present on the surface of a wide range of tumor cells. However, they have rarely been employed to transport photosensitizers (PS) for photodynamic therapy (PDT). Rhodamine (R) compounds have been dismissed as useful PSs for PDT due to their low O production, excitation wavelengths with little tissue penetration, and poor selectivity for tumor cells. It was recently demonstrated that when irradiating at 532 nm or with Cerenkov radiation (CR) from a β-emitting radionuclide, R123, R6G, and RB undergo electron transfer reactions (type I reaction) with folic acid. R6G also produces type I reactions with O. In this work, the photodynamic effects of the rHDL-R system were evaluated in vitro. rHDL nanoparticles loaded with R123, R6G, and RB were synthesized, and the PS was internalized into T47D tumor cells. When cells were irradiated with a 532-nm laser in the presence of an rHDL-R systems, a cytotoxic photodynamic effect was obtained in the order R6G > R123 > RB. In the presence of CR from a Lu source, cytotoxicity showed the order R6G > RB > R123. The higher cytotoxicity induced by R6G in both cases corresponds to higher cellular internalization and larger production of type I and II reactions. Thus, in this work, it is proposed that rHDL-R/Lu system can be applied in theragnostics as a multimodal radiotherapy-PDT-imaging system (imaging by SPECT or Cerenkov) and in hypoxic solid tumors in which external radiation is not effective and Lu-CR acts as light source.

Article	Year
Synthesis, chemical and biochemical characterization of LuO-iPSMA nanoparticles activated by neutron irradiation. Materials science & engineering. C, Materials for biological applications\| PubMed ID: 32919684	2020
Targeted photodynamic therapy using reconstituted high-density lipoproteins as rhodamine transporters. Photodiagnosis and photodynamic therapy\| PubMed ID: 34798347	2022

Nallely Patricia Jimenez-Mancilla

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