Abstract

ObjectivesPhotodynamic therapy (PDT) is a promising approach for cancer treatment, and the underlying signalling pathway changes has been carried out for studying the PDT mechanisms, but is majorly limited to organic photosensitizers (PSs). For the emerging nano‐PSs typically possessing higher 1O2 quantum yield, few mechanistic studies were carried out, which limited their further applications in clinical therapeutics. PI3K/Akt signalling pathway, a most frequently activated signalling network in cancers, could promote cancer cell survival, but was seldom reported in previous PDT studies mediated by nano‐PSs.Materials and MethodsSulphur doped carbon dots (S‐CDs) was prepared via a hydrothermal synthetic route and was characterized by transmission electron microscopy, X‐ray photoelectron spectroscopy and so on. CCK‐8 assay and Annexin V/PI staining were performed to demonstrate the death of cancer cells, Western blot, RT‐PCR and immunofluorescence were employed to explore the underlying mechanism, and variation of PI3K/Akt and other signalling pathways was detected by Western blot.ResultsS‐CDs was successfully synthesized, and it was much more efficient compared with classic organic PSs. S‐CDs could induce cancer cell death through mitochondria mediated cell apoptosis with the imbalance of Bcl‐2 family proteins and caspase cascade via several signalling pathways. Low concentration of S‐CDs could effectively inhibit PI3K/Akt pathway and promote p38/JNK pathway, on one way inhibiting cancer cell survival and on the other way promoting cell apoptosis.ConclusionsHerein, we found that S‐CDs acted as an inhibitor of the PI3K/Akt pathway for efficient cancer cell killing, thus yielding in a higher PDT performance over the existing photosensitizers.

Highlights

  • Glioblastoma multiforme is a malignant primary type of aggressive brain cancer with high proliferation and metastasis rates, and we found that sulphur doped carbon dots (S-CDs)-Photodynamic therapy (PDT) could efficiently induce apoptosis of glioblastoma cells (U87-MG) and inhibit PI3K/Akt signalling pathway

  • B, boosted Caspase-3 was observed after S-CDs mediated PDT. These results demonstrated that S-CDs induced cell apoptosis through mitochondria pathway with higher efficiency over the classical organic photosensitizers

  • The change of mitochondria pathway proteins and the inhibition of PI3K/Akt signalling pathway could be reserved after Vit C application (Figure 5C,D), indicating that reactive oxygen species (ROS) generated in cancer cells played a vital roles in the S-CDs-PDT mediated killing process

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Summary

| INTRODUCTION

Photodynamic therapy (PDT) shows important benefits in minimally invasive or even noninvasive, low toxicity, repeatability, good selectivity and widespread applicability.[1,2] Irradiation causes the photosensitizers (PSs) to transfer energy to molecular oxygen to generate reactive oxygen species (ROS), especially yield singlet oxygen (1O2), which subsequently oxidizes biomolecules in the photosensitized tissue, inducing cell death and tumour elimination.[3,4] Based on previous studies, cell apoptosis is reported the most majority mode of cell death in organic PSs-based PDT, which is induced by the change of apoptosis-related biomolecules such as calcium, cytochrome C. Glioblastoma multiforme is a malignant primary type of aggressive brain cancer with high proliferation and metastasis rates, and we found that S-CDs-PDT could efficiently induce apoptosis of glioblastoma cells (U87-MG) and inhibit PI3K/Akt signalling pathway. Another cancer cell line A375 (melanoma cell) was employed to further demonstrate the inhibition of PI3K/Akt during S-CDs-PDT, and the results showed efficient inhibition of PI3K/Akt and cancer cell survival. By detecting the changes of biomolecules in these cancer cells, including apoptotic factors, apoptotic proteins and signalling pathway proteins, the negative regulator effect of the S-CDs to the PI3K/Akt pathway was demonstrated

| MATERIALS AND METHODS
Findings
| DISCUSSION
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