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Gang Zheng

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    MA12 - Mesothelioma Surgery and Novel Targets for Prognosis and Therapy (ID 913)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 202 BD
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      MA12.09 - Preclinical Investigations of Folate Receptor Targeted Nanoparticles for Photodynamic Therapy of Malignant Pleural Mesothelioma (ID 11277)

      11:30 - 11:35  |  Author(s): Gang Zheng

      • Abstract
      • Presentation
      • Slides


      Photodynamic therapy (PDT) following lung-sparing extended pleurectomy (EPD) for malignant pleural mesothelioma (MPM) has been investigated as a potential means to kill residual microscopic cells. High expression of folate receptor 1 (FOLR1) has been reported in MPM, and targeting the FOLR1 has been considered as a new potential strategy. We have developed FOLR1-targeting porphyrin-lipid nanoparticles (folate-porphysomes; FP) for PDT. The inhibition of survival pathways of activated epidermal growth factor (EGFR) also enhance the PDT efficacy. Here, we have combined these approaches by using FP based PDT together with an EGFR-tyrosine kinase inhibitor (EGFR-TKI).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The frequency of FOLR1 and EGFR expression in MPM was analyzed using tissue microarrays. Confocal microscopy and a cell viability assay were performed to confirm the specificity of FOLR1-targeting cellular uptake and photocytotoxicity in vitro. In vivo fluorescence activation and the therapeutic efficacy were then examined. The effect of EGFR-TKI was assessed in vitro. The in vivo combined anti-tumor effect of EGFR-TKI and FP-PDT was then evaluated.

      4c3880bb027f159e801041b1021e88e8 Result

      FOLR1 and EGFR were expressed in 79 % and 89 % of the MPM samples, respectively. The intracellular uptake of FP corresponded well with FOLR1 expression. When MPM cells were incubated in FP and then irradiated at 671 nm, there was significant in vitro cell kill, which was inhibited in the presence of free folic acid, suggesting the specificity of FPs. FOLR1 targeting resulted in disassembly of the porphysomes and subsequent fluorescence activation in intrathoracic disseminated MPM tumors, as demonstrated by ex vivo tissue imaging. FP-PDT resulted in significant cellular damage and apoptosis in vivo. Furthermore, the combination of pre-treatment with EGFR-TKI plus FP-PDT showed further marked improvement of treatment responses.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Folate-porphysome based PDT shows selective destruction of MPM cells based on FOLR1 targeting, and pre-treatment with EGFR-TKI further enhances the therapeutic response.


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