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The Ability of Functionalized Fullerenes and Surface Modified TiO <sub/>2</sub> Nanoparticles to Photosensitize Peroxidation of Lipids in Selected Model Systems
摘要： Photochemical properties of a new class of inorganic nanoparticles, namely a cationic C60 fullerene substituted with three quaternary pyrrolidinium groups (BB6) and a surface modified nanocrystalline TiO2 with bromopyrogallol red (Brp@TiO2) were examined for their effectiveness in photogenerating singlet oxygen and free radicals. In particular, their ability to photosensitize peroxidation of unsaturated lipids was analyzed in POPC:cholesterol liposomes and B16 mouse melanoma cells employing a range of spectroscopic and analytical methods. Because melanoma cells typically are pigmented, we examined the effect of melanin on the photosensitized peroxidation of lipids in liposomes and B16 melanoma cells, mediated by BB6 and Brp@TiO2 nanoparticles. The obtained results suggest that peroxidation of unsaturated lipids, photosensitized by BB6 occurs mainly, although not exclusively, via Type II mechanism involving singlet oxygen. On the other hand, if surface modified TiO2 is used as a photosensitizer, Type I mechanism of lipid peroxidation dominates, as indicated by the predominant formation of the free-radical dependent cholesterol oxidation products. The protective effect of melanin was particularly evident when BB6 was used as a photosensitizer, suggesting that melanin could efficiently interfere with Type II processes.
关键词： Lipid peroxidation,Melanin,Fullerenes,Singlet oxygen,TiO2 nanoparticles,Free radicals,Photodynamic therapy
更新于2025-09-10 09:29:36
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Non-invasive dynamic assessment of conjunctival melanomas using photoacoustic imaging
摘要： This study describes non-invasive photoacoustic imaging to detect and monitor the growth of conjunctival melanomas in vivo. Conjunctival melanomas were induced by injection of melanotic B16F10 cells into the subconjunctival space in syngeneic albino C57BL/6 mice. Non-invasive in vivo photoacoustic tomography was performed before, and after tumor induction up to 2 weeks. Spectral unmixing was performed to determine the location and to assess the distribution of melanin. The melanin photoacoustic signal intensity was quantified from the tumor-bearing and control eyes at all timepoints. For postmortem validation, total tumor and melanotic tumor volumes were measured using H&E stained tumor sections and were compared to in vivo photoacoustic imaging measurements. Photoacoustic imaging non-invasively detected eyes bearing conjunctival tumors of varying sizes. The melanin signal was detected as early as immediately following injection of melanotic tumor cells. Changes in tumor size over time were assessed with changes in the volume and intensity of the melanin signal. Four growing tumors and one regressing tumor were observed. Three tumors without significant change in signal intensity over time were observed, showing variable growth. Photoacoustic melanin signal on the last day of in vivo imaging correlated with postmortem total tumor volume (R2 = 0.81) and melanotic tumor volume (R2 = 0.80). The results of our study show that the growth of conjunctival melanomas can be quantified in a non-invasive manner using in vivo photoacoustic tomography. The photoacoustic melanin signal intensity correlated with total and melanotic tumor volume. This novel in vivo imaging platform may aid in assessing new treatment modalities to treat ocular tumors.
关键词： near-infrared,mouse,melanin detection,photoacoustic imaging,oncology,in vivo,ocular melanoma
更新于2025-09-10 09:29:36
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Nanosonosensitizers for Highly Efficient Sonodynamic Cancer Theranostics
摘要： Background: Multifunctional nanoplatforms with diagnostic-imaging and targeted therapeutic functionality (theranostics) are of great interest in the field of precision nanomedicine. The emerging sonodynamic therapy (SDT) combined with sonosensitizers under the guidance of photoacoustic (PA) imaging is highly expected to accurately eliminate cancer cells/tissue. Methods: Unique core/shell-structured theranostic FA-HMME-MNPs-PLGA nanoparticles (FHMP NPs, FA: folate, HMME: hematoporphyrin monomethyl ether, MNPs: melanin nanoparticles, PLGA: poly (lactic-co-glycolic) acid) were constructed by the integration of MNPs (for PA imaging) in the core and HMME in the shell for enhanced PA imaging-guided SDT, which were further functionalized with a tumor-targeting ligand, FA. The PA imaging-guided SDT was systematically and successfully demonstrated both in vitro and in vivo. The high biosafety of FHMP NPs was also systematically evaluated. Results: The synthesized FHMP NPs with a broad optical absorption not only possess high PA-imaging contrast enhancement capability but also exhibit significant SDT efficiency. Importantly, such a PLGA based nanoplatform improved light stability of HMME, enhancing sonodynamic performance and facilitated delivery of MNPs to the tumor region. Meanwhile, a combined effect between HMME and MNPs was discovered and verified. Furthermore, a sonosensitizer assisted by ultrasound irradiation engenders reactive oxygen species (ROS)-mediated cytotoxicity toward tumor cells/tissue. Both in vitro cell-level and systematic in vivo xenograft evaluations on tumor-bearing mice demonstrated that the selective killing effect of ROS on tumor cells was assisted by FHMP NPs, which played an active role in the suppression of tumor growth with high biosafety. Conclusion: A theranostic nanoplatform was successfully constructed, achieving PA imaging-guided SDT against breast cancer cells/tissue. More importantly, MNPs and HMME in one platform with combined effect for enhancing PA imaging was demonstrated. This unique theranostic nanoplatform with multiple capabilities paves a new way toward personalized medicine by rational utilization.
关键词： Nanosonosensitizers,Nanomedicine,Sonodynamic therapy,Photoacoustic imaging,HMME,Melanin
更新于2025-09-09 09:28:46
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Gadolinium Doping Enhances the Photoacoustic Signal of Synthetic Melanin Nanoparticles: A Dual Modality Contrast Agent for Stem Cell Imaging.
摘要： In this paper we show that gadolinium-loaded synthetic melanin nanoparticles (Gd(III)-SMNPs) exhibit up to a 40-fold enhanced photoacoustic signal intensity relative to synthetic melanin alone and higher than other metal-chelated SMNPs. This property makes these materials useful as dual labelling agents because Gd(III)-SMNPs also behave as magnetic resonance imaging (MRI) contrast agents. As a proof-of-concept, we used these nanoparticles to label human mesenchymal stem cells (hMSCs). Cellular uptake was confirmed with bright field optical and transmission electron microscopy. The Gd(III)-SMNP labeled stem cells continued to express the stem cell surface markers CD73, CD90, and CD105 and proliferate. The labeled stem cells were subsequently injected intramyocardially in mice, and the tissue was observed by photoacoustic and MR imaging. We found the photoacoustic signal increased as cell number increased (R2 = 0.96) indicating that such an approach could be employed to discriminate between stem cells populations with a limit of detection of 2.3 x 104 cells in in vitro tests. This multimodal photoacoustic/MRI approach combines the excellent temporal resolution of photoacoustics with the anatomic resolution of MRI.
关键词： Photoacoustic Signal,Stem Cell Imaging,Gadolinium,Dual Modality Contrast Agent,Synthetic Melanin Nanoparticles
更新于2025-09-04 15:30:14
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Melanin Pigmentation in Rat Eyes: In Vivo Imaging by Polarization-Sensitive Optical Coherence Tomography and Comparison to Histology
摘要： The purpose of this study was to demonstrate polarization-sensitive optical coherence tomography (PS-OCT) for imaging pigmented structures in the posterior eye segments of albino and pigmented rats and to correlate depolarization contrast of the retinal pigment epithelium (RPE) and choroid in in vivo PS-OCT to melanin pigmentation detected in postmortem histologic serial sections. In vivo three-dimensional PS-OCT imaging was performed in adult albino and pigmented rat eyes at 70-kHz A-line rate. Degree of polarization uniformity (DOPU) fundus maps and radial DOPU pro?les were generated. Postmortem histomorphologic analysis was performed in order to investigate melanin pigmentation of the RPE and choroid. Fundus pigmentation maps were extracted from histologic serial sections. Pigmentation pro?les were correlated to DOPU pro?les of the same eyes. Strong depolarization was found in the RPE/choroid complex of pigmented rats, whereas the same structures exhibited uniform polarization in albino rats. The difference between the depolarization characteristics between albino and pigmented animals was statistically signi?cant. In the fundus pigmentation maps, optical pigment density was zero in albino rat eyes. In pigmented rat eyes, a strong negative correlation between optical pigment density and DOPU was observed. This in vivo and ex vivo investigation of posterior rat eyes indicates that melanin is the cause of depolarization in retinal PS-OCT images. It further demonstrates that melanin pigmentation in the RPE and choroid can be quanti?ed via depolarization imaging and therefore suggests that PS-OCT is a useful tool for the noninvasive quantitative assessment of pigmentary changes in vision-threatening diseases such as age-related macular degeneration.
关键词： choroid,melanin,optical coherence tomography,depolarization,retinal pigment epithelium,polarization sensitive devices
更新于2025-09-04 15:30:14