A novel multimodal nanoplatform for targeting tumor necrosis

Han, Xiangjun; Taratula, Oleh; Lorenz, Anna St; Moses, Abraham S.; Albarqi, Hassan A.; Jahangiri, Younes; Wu, Qirun; Xu, Ke; Taratula, Olena; Farsad, Khashayar

doi:10.1039/d1ra05658a

Cited by 1 publication

(5 citation statements)

References 54 publications

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“…The cryo-cell death model was created using lethal freezing temperature with dry ice as previously described. 17 As shown in Figure 4A, phase-contrast imaging demonstrated the abnormal morphology of cryo-necrotic cells in the left field of view. DAPI was used to assess cell permeation and nuclear staining.…”

Section: ■ Results and Discussionmentioning

confidence: 87%

“…Hemolysis evaluation was performed to investigate the compatibility of PNP@( 131 I-Hyp) by determining the amount of intact red blood cells according to previous research. 17 The hemolysis rates of the control group and tested groups with hypericin concentrations from 12.5 to 100 μg/mL (radioactive concentrations from 0.5 to 4.0 mCi/mL) were all lower than 5% without a significant difference, which revealed no significant hemolysis occurrence (Figure 3A). The hemolysis evaluation suggested that the PEG−PCL polymeric nanoparticles encapsulating hydrophobic 131 I-Hyp were suitable for in vivo delivery.…”

Section: ■ Results and Discussionmentioning

confidence: 92%

“…The hemolysis test and cytotoxicity assay were performed to evaluate the potential toxicity of the present polymeric nanoparticles. Hemolysis evaluation was performed to investigate the compatibility of PNP@( 131 I-Hyp) by determining the amount of intact red blood cells according to previous research . The hemolysis rates of the control group and tested groups with hypericin concentrations from 12.5 to 100 μg/mL (radioactive concentrations from 0.5 to 4.0 mCi/mL) were all lower than 5% without a significant difference, which revealed no significant hemolysis occurrence (Figure A).…”

Section: Resultsmentioning

confidence: 99%

“…To simulate the necrosis of tumor cells in vitro , freezing and hyperthermia procedures were conducted to induce the death of the SK-HEP-1 cells. The cryo-cell death model was created using lethal freezing temperature with dry ice as previously described . As shown in Figure A, phase-contrast imaging demonstrated the abnormal morphology of cryo-necrotic cells in the left field of view.…”

Section: Resultsmentioning

confidence: 99%

“…PNP@( 131 I-Hyp) nanoparticles were prepared using a modified solvent evaporation method according to previous research. 17 Briefly, 1 mL of 131 I-Hyp solution, 20 mg of PEG−PCL, and 1.5 mL of acetone were mixed at 45 °C in a shaking incubator at 150 rpm for 30 min. During the mixing process, 1.5 mL of saline was added to the reaction system.…”

Section: ■ Introductionmentioning

confidence: 99%

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Multimodal Theranostic Nanoparticles for Necrosis Targeting, Fluorescence/SPECT Imaging, and Radiotherapy of Residual Tumors after Hepatocellular Carcinoma Ablation

Bao,

Wang,

Chen

et al. 2024

Mol. Pharmaceutics

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Thermal ablation has been commonly used as an effective treatment for hepatocellular carcinoma; however, perinecrotic tumor residues after ablation play a significant role in tumor recurrence and poor prognosis. Therefore, developing agents that can effectively target and eliminate residual tumors is critically needed. Necrosis targeting strategies have potential implications for evaluating tumor necrosis areas and treating the surrounding residual tumors. To address this issue, we have developed a biodegradable nanoparticle with necrosis avidity that is compatible with fluorescence imaging, single photon emission computed tomography (SPECT) imaging, and necrosis targeted radiotherapy. The nanoparticles were synthesized using iodine-131-labeled hypericin ( 131 I-Hyp) as the core and amphiphilic copolymer poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG−PCL) as the shell. The developed nanoparticle, PNP@( 131 I-Hyp), has a uniform spherical morphology with a size of 33.07 ± 3.94 and 45.93 ± 0.58 nm determined by cryogenic transmission electron microscopy (cryo-TEM) and dynamic lightscattering analysis (polydispersity index = 0.19 ± 0.01), respectively, and having a good stability and blood compatibility in vitro. In mouse subcutaneous ablated-residual tumor models, fluorescence and SPECT imaging demonstrated that PNP@( 131 I-Hyp) prominently accumulated in the tumor and was retained for as long as 168 h following intravenous injection. Moreover, ex vivo analyses showed that PNP@( 131 I-Hyp) mainly gathered in the necrotic zones of subcutaneous tumors and inhibited residual tumors by radiotherapy. In addition, histological examination of harvested organs and hematological analysis demonstrated that intravenous injection of 5 mCi/kg nanoparticles caused no gross abnormalities. This multifunctional nanoparticle, therefore, has necrosis imaging and targeted therapeutic effects on residual tumors after thermal ablation of hepatocellular carcinoma, showing potential for clinical application.

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Section: ■ Results and Discussionmentioning

confidence: 87%

Section: ■ Results and Discussionmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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