DataVXACS Applied Nano MaterialsPaper
journal article·2021-01-22

Doxorubicin-Conjugated Platinum Theranostic Nanoparticles Induce Apoptosis via Inhibition of a Cell Survival (PI3K/AKT) Signaling Pathway in Human Breast Cancer Cells

Puja Patel, Vinita Manimaran Nadar, Devan Umapathy, Selvambigai Manivannan, Rajiu Venkatesan, Velanganni Antony Joseph Arokiyam, Srinivasan Pappu, Pitchan Arul Prakash, Mohamed Sultan Mohamed Jabir, Balázs Gulyás, Parasuraman Padmanabhan, Subramanian Tamil Selvan, Ponnuchamy Kumar

ACS Applied Nano Materials· Volume 4· Issue 1
Publisher page
Source abstract

Abstract

Herein, we report facile theranostic platinum nanoparticles (PtNPs) conjugated to an anticancer drug, doxorubicin (DOX), in unraveling the inhibition of a cell survival PI3K/AKT (phosphatidylinositol 3-kinase/protein kinase B) signaling pathway in MCF-7 and MDA-MB-231 human breast cancer cells. The significant features of our DOX@PtNPs as a theranostic platform are as follows: (i) drug release studies showed a progressive pH-dependent delivery; (ii) in vitro studies of DOX@PtNPs displayed a relatively higher cytotoxicity to breast cancer cells compared to unconjugated PtNPs and DOX; (iii) intracellular drug release studies showed a specific binding of DOX@PtNPs and their release within the cytoplasm and perinuclear region; (iv) DOX@PtNPs induced the apoptosis of cancer cells by DNA damage via the generation of elevated levels of reactive oxygen species and decreased mitochondrial membrane potential (ΔΨm), as evidenced by fluorescence microscopic studies; and (v) DOX@PtNPs inhibited the PI3K/AKT signaling pathway in breast cancer cells by activating PTEN, a tumor suppressor gene. The induced mitochondrial-dependent apoptotic pathway led to the activation of downstream caspases. Finally, our findings illustrate that DOX@PtNPs may serve as a better theranostic agent for cancer nanomedicine.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Metal complexes synthesis and properties · Advanced biosensing and bioanalysis techniques · Advanced Nanomaterials in Catalysis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Food Chemistry and Molecular Cancer Biology Lab, Department of Animal Health and Management, Alagappa University, Karaikudi 630003, Tamil Nadu, India

Molecular Oncology Lab, Department of Biochemistry, Bharathidasan University, Tiruchirappalli 620024, Tamil Nadu, India

Department of Biomedical Science and Centre for Membrane Interactions and Dynamics (CMIAD), The University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China

Phage Therapy and Molecular Biology Lab, Department of Animal Health and Management, Alagappa University, Karaikudi 630003, Tamil Nadu, India

PG and Research Department of Biotechnology and Microbiology, The National College, Tiruchirappalli 620001, Tamil Nadu, India

Translational Neuroscience Laboratory, Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Singapore 636921, Singapore

Funding

Indian Council of Medical Research · Austrian Institute of Technology · Science and Engineering Research Board · Ministry of Human Resource Development · Medizinische Universit?t Wien · Nanyang Technological University

References (67)

Show source-provided references
1. 10.1002/anie.20060424510.1002/anie.200604245 ↗
2. 10.1021/ja042886310.1021/ja0428863 ↗
3. 10.1021/la903512m10.1021/la903512m ↗
4. 10.7150/thno.482710.7150/thno.4827 ↗
5. 10.1021/nn401734t10.1021/nn401734t ↗
6. 10.1016/j.actbio.2016.06.00310.1016/j.actbio.2016.06.003 ↗
7. 10.7150/thno.369210.7150/thno.3692 ↗
8. 10.1016/j.bioorg.2017.12.03310.1016/j.bioorg.2017.12.033 ↗
9. 10.1016/j.ijpharm.2015.04.02810.1016/j.ijpharm.2015.04.028 ↗
10. 10.1080/1061186x.2017.140055310.1080/1061186x.2017.1400553 ↗
11. 10.1016/j.actbio.2016.11.06610.1016/j.actbio.2016.11.066 ↗
12. 10.1021/acsanm.9b0063410.1021/acsanm.9b00634 ↗
13. 10.1021/acsanm.0c0059810.1021/acsanm.0c00598 ↗
14. 10.1002/cplu.20150034910.1002/cplu.201500349 ↗
15. 10.1016/j.actbio.2020.03.04710.1016/j.actbio.2020.03.047 ↗
16. 10.1002/(sici)1521-4095(199801)10:2<132::aid-adma132>3.0.co;2-y10.1002/(sici)1521-4095(199801)10:2<132::aid-adma132>3.0.co;2-y ↗
17. 10.1021/acsnano.5b0474410.1021/acsnano.5b04744 ↗
18. 10.1002/adma.20170700310.1002/adma.201707003 ↗
19. 10.1002/adma.20040196010.1002/adma.200401960 ↗
20. 10.1039/c2sc21191b10.1039/c2sc21191b ↗
21. 10.1021/acs.jpcc.5b0842310.1021/acs.jpcc.5b08423 ↗
22. 10.1016/j.apcatb.2017.05.01710.1016/j.apcatb.2017.05.017 ↗
23. 10.1016/j.bios.2018.08.02210.1016/j.bios.2018.08.022 ↗
24. 10.1021/acsami.9b0840810.1021/acsami.9b08408 ↗
25. 10.1016/j.mattod.2018.08.00510.1016/j.mattod.2018.08.005 ↗
26. 10.1021/jp709767910.1021/jp7097679 ↗
27. 10.1021/ja107333g10.1021/ja107333g ↗
28. 10.1021/acsami.7b1470510.1021/acsami.7b14705 ↗
29. 10.2217/nnm-2017-022810.2217/nnm-2017-0228 ↗
30. 10.3390/nano908108910.3390/nano9081089 ↗
31. 10.2147/ijn.s13093810.2147/ijn.s130938 ↗
32. 10.1016/j.jcis.2020.02.05110.1016/j.jcis.2020.02.051 ↗
33. 10.1016/j.jddst.2020.10174910.1016/j.jddst.2020.101749 ↗
34. 10.1039/c2tb00078d10.1039/c2tb00078d ↗
35. 10.1016/j.cbi.2018.03.01610.1016/j.cbi.2018.03.016 ↗
36. 10.1016/j.btre.2019.e0033910.1016/j.btre.2019.e00339 ↗
37. 10.1016/j.msec.2019.11037510.1016/j.msec.2019.110375 ↗
38. 10.1080/17458080.2010.51301710.1080/17458080.2010.513017 ↗
39. 10.1155/2016/965163710.1155/2016/9651637 ↗
40. 10.1021/la501109g10.1021/la501109g ↗
41. 10.1021/acsanm.0c0105810.1021/acsanm.0c01058 ↗
42. 10.1039/c5dt02964c10.1039/c5dt02964c ↗
43. 10.1039/c6tb02071b10.1039/c6tb02071b ↗
44. 10.1016/j.snb.2017.11.04410.1016/j.snb.2017.11.044 ↗
45. 10.1016/j.jiec.2017.03.02910.1016/j.jiec.2017.03.029 ↗
46. 10.1021/la100575g10.1021/la100575g ↗
47. 10.1039/c6ra18050g10.1039/c6ra18050g ↗
48. 10.1098/rsos.18056410.1098/rsos.180564 ↗
49. 10.3390/ijms1801012010.3390/ijms18010120 ↗
50. 10.1038/srep0825210.1038/srep08252 ↗
51. 10.1371/journal.pone.008461010.1371/journal.pone.0084610 ↗
52. 10.4155/fmc-2017-001110.4155/fmc-2017-0011 ↗
53. 10.3892/mmr.2019.1012110.3892/mmr.2019.10121 ↗
54. 10.1186/s12943-019-0954-x10.1186/s12943-019-0954-x ↗
55. 10.1186/s12943-018-0803-310.1186/s12943-018-0803-3 ↗
56. 10.1186/s40880-019-0412-610.1186/s40880-019-0412-6 ↗
57. 10.3390/ijms2109336310.3390/ijms21093363 ↗
58. 10.1038/s41598-020-66428-510.1038/s41598-020-66428-5 ↗
59. 10.1101/cshperspect.a00871410.1101/cshperspect.a008714 ↗
60. 10.1038/nrm372210.1038/nrm3722 ↗
61. 10.1016/j.mito.2011.01.01010.1016/j.mito.2011.01.010 ↗
62. 10.1016/j.ymeth.2013.03.03010.1016/j.ymeth.2013.03.030 ↗
63. 10.1038/s41419-018-0408-110.1038/s41419-018-0408-1 ↗
64. 10.1146/annurev-genet-102108-13485010.1146/annurev-genet-102108-134850 ↗
65. Estaquier J. · 2012 · 942 · 15710.1007/978-94-007-2869-1_7 ↗
66. 10.1101/cshperspect.a00608010.1101/cshperspect.a006080 ↗
67. 10.1016/s0092-8674(02)00802-410.1016/s0092-8674(02)00802-4 ↗