Phycocyanin-functionalized black phosphorus quantum dots enhance PDT/PTT therapy by inducing ROS and irreparable DNA damage

2021 ◽  
Author(s):  
Wanheng Zhang ◽  
Liting Yu ◽  
Yin Jiang ◽  
Changying Guo

The novel phycocyanin (PC)-functionalized black phosphorus quantum dots (BPQDs) achieve synergistic photodynamic and photothermic activity by inducing massive ROS and irreparable DNA damage, resulting in increased apoptosis in vitro and tumor eradication in vivo.

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 242 ◽  
Author(s):  
Miaomiao Luo ◽  
Wei Cheng ◽  
Xiaowei Zeng ◽  
Lin Mei ◽  
Gan Liu ◽  
...  

Due to the inherent limitations, single chemo or photothermal therapies (PTT) are always inefficient. The combination of chemotherapy and PTT for the treatment of cancers has attracted a great interest during the past few years. As a photothermal agent, black phosphorus quantum dots (BPQDs) possess an excellent extinction coefficient, high photothermal conversion efficacy, and good biocompatibility. Herein, we developed a photo- and pH-sensitive nanoparticle based on BPQDs for targeted chemo-photothermal therapy. Doxorubicin (DOX) was employed as a model drug. This nanosystem displayed outstanding photothermal performance both in vitro and in vivo. Folic acid conjugation onto the surface endowed this system an excellent tumor-targeting effect, which was demonstrated by the cellular targeting assay. The BPQDs-based drug delivery system exhibited pH- and photo-responsive release properties, which could reduce the potential damage to normal cells. The in vitro cell viability study showed a synergistic effect in suppressing cancer cell proliferation. Therefore, this BPQDs-based drug delivery system has substantial potential for future clinical applications.


Nanophotonics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 2425-2435 ◽  
Author(s):  
Jing Wang ◽  
Dong Liang ◽  
Zehua Qu ◽  
Ivan M. Kislyakov ◽  
Valery M. Kiselev ◽  
...  

AbstractBiological systems have high transparence to 700–1100-nm near-infrared (NIR) light. Black phosphorus quantum dots (BPQDs) have high optical absorbance in this spectrum. This optical property of BPQDs integrates both diagnostic and therapeutic functions together in an all-in-one processing system in cancer theranostic approaches. In the present study, BPQDs were synthesized and functionalized by targeting moieties (PEG-NH2-FA) and were further loaded with anticancer drugs (doxorubicin) for photodynamic–photothermal–chemotherapy. The precise killing of cancer cells was achieved by linking BPQDs with folate moiety (folic acid), internalizing BPQDs inside cancer cells with folate receptors and NIR triggering, without affecting the receptor-free cells. These in vitro experiments confirm that the agent exhibited an efficient photokilling effect and a light-triggered and heat-induced drug delivery at the precise tumor sites. Furthermore, the nanoplatform has good biocompatibility and effectively obliterates tumors in nude mice, showing no noticeable damages to noncancer tissues. Importantly, this nanoplatform can inhibit tumor growth through visualized synergistic treatment and photoacoustic and photothermal imaging. The present design of versatile nanoplatforms can allow for the adjustment of nanoplatforms for good treatment efficacy and multiplexed imaging, providing an innovation for targeted tumor treatment.


2019 ◽  
Vol 43 (22) ◽  
pp. 8620-8626
Author(s):  
Chengkang Su ◽  
Huiqing Zhong ◽  
Haolin Chen ◽  
Yanxian Guo ◽  
Zhouyi Guo ◽  
...  

Black phosphorus–polypyrrole nanosheets with superimposed NIR absorption have been fabricated as the novel nanotherapeutic agent for enhanced NIR photothermal cancer therapy in vitro and in vivo.


Small ◽  
2017 ◽  
Vol 13 (11) ◽  
pp. 1602896 ◽  
Author(s):  
Zhengbo Sun ◽  
Yuetao Zhao ◽  
Zhibin Li ◽  
Haodong Cui ◽  
Yayan Zhou ◽  
...  

2009 ◽  
Vol 30 (2) ◽  
pp. 524-536 ◽  
Author(s):  
Luis A. Martinez ◽  
Elzbieta Goluszko ◽  
Hui-Zi Chen ◽  
Gustavo Leone ◽  
Sean Post ◽  
...  

ABSTRACT The E2F transcription factors have emerged as critical apoptotic effectors. Herein we report that the E2F family member E2F3a can be induced by DNA damage through transcriptional and posttranslational mechanisms. We demonstrate that the posttranslational induction of human E2F3a is dependent on the checkpoint kinases. Moreover, we show that human E2F3a is a substrate for the checkpoint kinases (chk kinases) and that mutation of the chk phosphorylation site eliminates the DNA damage inducibility of the protein. Furthermore, we demonstrate that E2F1 and E2F2 are transcriptionally induced by DNA damage in an E2f3-dependent manner. Finally, using both in vitro and in vivo approaches, we establish that E2f3 is required for DNA damage-induced apoptosis. Thus, our data reveal the novel ability of E2f3 to function as a master regulator of the DNA damage response.


2019 ◽  
Vol 19 (3) ◽  
pp. 365-374 ◽  
Author(s):  
Yang Liu ◽  
Jingyin Zhang ◽  
Shuyun Feng ◽  
Tingli Zhao ◽  
Zhengzheng Li ◽  
...  

Objective: The aim of this study is to investigate the inhibitory effect of camptothecin derivative 3j on Non-Small Cell Lung Cancer (NSCLCs) cells and the potential anti-tumor mechanisms. Background: Camptothecin compounds are considered as the third largest natural drugs which are widely investigated in the world and they suffered restriction because of serious toxicity, such as hemorrhagic cystitis and bone marrow suppression. Methods: Using cell proliferation assay and S180 tumor mice model, a series of 20(S)-O-substituted benzoyl 7- ethylcamptothecin compounds were screened and evaluated the antitumor activities in vitro and in vivo. Camptothecin derivative 3j was selected for further study using flow cytometry in NSCLCs cells. Cell cycle related protein cyclin A2, CDK2, cyclin D and cyclin E were detected by Western Blot. Then, computer molecular docking was used to confirm the interaction between 3j and Topo I. Also, DNA relaxation assay and alkaline comet assay were used to investigate the mechanism of 3j on DNA damage. Results: Our results demonstrated that camptothecin derivative 3j showed a greater antitumor effect in eleven 20(S)-O-substituted benzoyl 7-ethylcamptothecin compounds in vitro and in vivo. The IC50 of 3j was 1.54± 0.41 µM lower than irinotecan with an IC50 of 13.86±0.80 µM in NCI-H460 cell, which was reduced by 8 fold. In NCI-H1975 cell, the IC50 of 3j was 1.87±0.23 µM lower than irinotecan (IC50±SD, 5.35±0.38 µM), dropped by 1.8 fold. Flow cytometry analysis revealed that 3j induced significant accumulation in a dose-dependent manner. After 24h of 3j (10 µM) treatment, the percentage of NCI-H460 cell in S-phase significantly increased (to 93.54 ± 4.4%) compared with control cells (31.67 ± 3.4%). Similarly, the percentage of NCI-H1975 cell in Sphase significantly increased (to 83.99 ± 2.4%) compared with control cells (34.45 ± 3.9%) after treatment with 10µM of 3j. Moreover, increased levels of cyclin A2, CDK2, and decreased levels of cyclin D, cyclin E further confirmed that cell cycle arrest was induced by 3j. Furthermore, molecular docking studies suggested that 3j interacted with Topo I-DNA and DNA-relaxation assay simultaneously confirmed that 3j suppressed the activity of Topo I. Research on the mechanism showed that 3j exhibited anti-tumour activity via activating the DNA damage response pathway and suppressing the repair pathway in NSCLC cells. Conclusion: Novel camptothecin derivative 3j has been demonstrated as a promising antitumor agent and remains to be assessed in further studies.


ACS Nano ◽  
2018 ◽  
Vol 12 (12) ◽  
pp. 12401-12415 ◽  
Author(s):  
Leung Chan ◽  
Pan Gao ◽  
Wenhua Zhou ◽  
Chaoming Mei ◽  
Yanyu Huang ◽  
...  

Nanophotonics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 3023-3034
Author(s):  
Weiyuan Liang ◽  
Dou Wang ◽  
Xiaohui Ren ◽  
Chenchen Ge ◽  
Hanyue Wang ◽  
...  

AbstractTwo-dimensional black phosphorus (BP) has been demonstrated to be promising in photoelectronic devices, electrode materials, and biomedicine owing to its outstanding properties. However, the application of BP has been hindered by harsh preparation conditions, high costs, and easy degradation in ambient condition. Herein, we report a facile and cost-effective strategy for synthesis of orthorhombic phase BP and a kind of BP-reduced graphene oxide (BP/rGO) hybrids in which BP remains stable for more than 4 weeks ascribed to the formation of phosphorus-carbon covalent bonds between BP and rGO as well as the protection effect of the unique wrinkle morphology of rGO nanosheets. Surface modification BP/rGO hybrids (PEGylated BP/rGO) exhibit excellent photothermal performance with photothermal conversion efficiency as high as 57.79% at 808 nm. The BP/rGO hybrids exhibit enhanced antitumor effects both in vitro and in vivo, showing promising perspectives in biomedicine.


Biomarkers ◽  
2021 ◽  
pp. 1-9
Author(s):  
Habiba Bouchab ◽  
Abbas Ishaq ◽  
Riad EL Kebbaj ◽  
Boubker Nasser ◽  
Gabriele Saretzki

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