Title: A smart stride for cancer: synergistic effect of co-delivery chemo- and phototherapeutic agents using magneto-fluorescent multi-walled carbon nanotubes against persistent cancer cells.
Funding Source: POLONEZ In a combined action of the National Science Centre Poland and the EU’s Horizon 2020 program under the Marie Skłodowska-Curie grant agreement
Grant Number: UMO-2022/45/P/NZ7/03645
Project Number: 2022/45/P/NZ7/03645
Principal Investigator: Dr. Prachi Ghoderao
ghoderao.prachi@gmail.com
Background and research aims:
Cancer is the second leading cause of mortality and the main obstacle to increasing life expectancy in almost every country of the World. According to estimates from GLOBOCAN, there were 19.3 million new cases and 10 million cancer deaths worldwide in 2020; and it is expected 28.4 million cases in 2040, an unfortunate 47% rise from 2020. The currently available chemotherapeutic treatments show the following general shortcomings: a) poor bioavailability: less therapeutic effect; b) non-targeted therapy: drugs striking non-diseased/healthy cells; c) targeting cancer stem cells (CSCs) is difficult: relapse/recurrence of tumor; d) induce/select drug-resistant persistent cancer cells (PCCs): show specific characteristics leading to drug resistance; e) frequent high dosage: hepatotoxicity, gastric intolerance, hypersensitivity, nephrotoxicity, hematological reactions, and neurological effects. Based on the above-stated pitfalls of the currently available chemotherapeutic treatments, the newly developed drug delivery systems should favor the detection and direction of the drug inside the body. This strategy should also eliminate cancer cells and prevent PCCs emergence. These systems also should have control to take the drug at the respective site of action, which consequently leads to improve the bioavailability and can specifically target the diseased tissues only, keeping intact and safe healthy cells (fewer side-effects and toxicity). Better assimilation of the drug in the body and enhanced membrane transport ability of the drug should be focused. Once the new strategically developed drug is delivered at the right place, in the right concentration, and maintained the desired concentration for the appropriate duration should be achieved by deriving smart control over the drug release. Eventually, it turns into improved efficacy of the drug and protects the drug from unwanted degradation.
In this project, we have proposed the formulation of a smart combination of super-functionalization of MWCNTs: i) internally with Fe3O4 (Mag) and ii) externally with gold nanoparticles (Au NPs), Doxorubicin (DOX), anti-CD44 antibodies (Ab CD44), and siRNA/ALDH (siALDH). When used in combination, it will produce synergistic effects and enhance the efficacy of killing PCCs. Altogether, through inter-disciplinary collaborations, our proposed work focuses to develop a new strategy to target cancer cells and particularly PCCs to diminish the possibilities of cancer recurrence.
Specific Research goals:
The expected benefits of the research work to be carried out through the POLONEZ fellowship will focus on the different aspects of nanotechnology in drug delivery i.e., targeted drug delivery, prompt cellular uptake of the developed drug-nanomaterial complex employing the specific constituents used in the complex development like 1 D MWCNTs with the betterment of the drug’s efficacy.
Detail analysis of the developed complex may show better therapy and treatment option with this new approach to eradicating the disease. Subsequently, this will open the window for enhanced efficacy and better therapy. Precisely, the design and development of drug complex lead to the appropriate therapy with higher efficacy than that of the conventional drug.
Duration: 24 Months
Budget: PLN 1 103 172,00
Team Members:
Dr. Prachi Ghoderao
Principal Investigator
The PI is a recipient of the prestigious MSCA-POLONEZ BIS 2 fellowship (2023). And also she won The renowned Fondecyt Fellowship, Chile. She has completed her master’s in analytical chemistry from the University of Pune and was awarded Ph.D. (2021) from the Defence Institute of Advanced Technology, Pune, India, in the area of development of drug nanoparticle complexes to improve drug efficacy. In her Ph.D. tenure, she received the “Jyotiba Phule National Research Fellowship” awarded by BARTI, Pune, India. Her research interests focus on materials chemistry, nanotechnology, cancer research, and drug delivery. In summary, the work focused on developing an efficacious drug delivery system based on diverse nanomaterials and their tailored functionalization with specific entities, thereby enhancing cellular internalization and enabling targeted drug delivery.
Hanna Dams-Kozlowska
Mentor
The mentor has been serving as an Associate Professor at Poznan University of Medical Sciences, Poznań, Poland, since 2022. Her primary research interests focus on bioengineered silk-based materials as effective drug delivery systems for cancer therapy. Since 2010, numerous students have joined her research group, significantly accelerating research activities and scientific output. A major outcome of her work is the design and characterization of H2.1MS1, a hybrid protein composed of silk (MS1) and a HER2-binding peptide (H2.1). Particles fabricated from H2.1MS1 were shown to selectively target HER2-overexpressing cancer cells and, when loaded with doxorubicin, effectively eliminated targeted cancer cells both in vitro and in vivo. Importantly, these studies demonstrated that targeted drug delivery systems that promote cellular internalization of the carrier are substantially more effective than systems relying solely on the accumulation of drug carriers within the tumor microenvironment.
Mrs. Marta Krueger,
Administrative Assistant
An archaeologist by profession, has worked at the PUMS in the Department of Science, Project Acquisition and International Cooperation since 2023. Her main task in the project is to support the PI in matters related to the administrative and financial aspects of the project and to be a guide through the world of bureaucracy.
PI’s Publications
Sanjay Sahare, Prachi Ghoderao, Manish Kumar Sharma, Mykhailo Solovan, Radhamanohar Aepuru, Manjeet Kumar, Yue Chan, Marcin Ziółek, Shern-Long Lee, Zong-Hong Lin, Pyro-phototronic effect: An effective route toward Self-powered photodetection, Nano Energy, 107 (2023) 105172. (I.F. 19.06).
Sanjay Sahare, Prachi Ghoderao, Yue Chan, Shern-Long Lee*, Surface supramolecular assemblies tailored by chemical/physical and synergistic stimuli: scanning tunneling microscopy reveals, Nanoscale 15 (2023) 1981. (I.F. 8.3). (Featured as a cover page)
Sanjay Sahare, Prachi Ghoderao, Peng Yin, Awais Siddique Saleemi, Shern-Long Lee*, Yue Chan, and Han Zhang*, “An assessment of MXenes through Scanning Probe Microscopy”, Small Methods 6 (2022) 202101599. (I.F. 15.36)
Sanjay Sahare, H. D. Pham, Dechan Angmo, Prachi Ghoderao, Jennifer MacLeod, S. B. Khan, Shern-Long Lee, S. P. Singh, Prashant Sonar, “Emerging perovskite solar cell technology: Remedial actions for the foremost challenges, Advanced Energy Materials, 11 (2021) 2101085. (I.F. 29.67) (Featured in cover page)
Afagh Rastmanesh, Mohammad Tavakkoli Yaraki, Jinyu Wu, Zihao Wang, Prachi Ghoderao, Yongxiang Gao and Yen Nee Tan “Bioinspired Micro/Nanomotors Towards Self-powered Non-invasive Diagnosis and Treatment of Cancer” Mol. Syst. Des. Eng., 6 (2021) 566. (I.F. 4.92)
Sanjay Sahare, Prachi Ghoderao, Sadaf Bashir Khan, Yue Chan, and Shern-Long Lee, “Recent progress in hybrid perovskites solar cells through scanning tunnelling microscopy and spectroscopy”, Nanoscale, 12 (2020) 15970. (I.F. 8.3).
Prachi Ghoderao, Sanjay Sahare, Prashant Aalegaonkar, Anjali A. Kulkarni, and Tejashree Bhave, “Multiwalled Carbon Nanotubes Decorated with Fe3O4 Nanoparticles for Efficacious Doxycycline Delivery” ACS Applied Nanomaterials, 2 (2019) 607-616. (I.F. 6.1).
Naresh Veldurthi, Prachi Ghoderao, Sanjay Sahare, Vijay Kumar, Dhananjay Bodas, Anjali Kulkarni, Tejashree Bhave, “Magnetically active micromixer assisted synthesis of drug nanocomplexes exhibiting strong bactericidal potential”, Materials Science and Engineering C 68 (2016) 455–464. (NV and PG have contributed equally). (I.F. 7.3).
Tejashree Bhave, Prachi Ghoderao, Harshada Nagar, V. Ganesan, Sonali Sanghavi, Anjali Kulkarni, S.V. Bhoraskar, “Synthesis of biocompatible nanoparticle drug complexes for inhibition of mycobacteria”, Adv. Nat. Sci, Nanosci.Nanotechnol. 2 (2013) 7. (I.F. 2.37).
Sanjay Sahare, Manauti Salunkhe, Prachi Ghoderao, and Tejashree Bhave, “Surfactant modified Bi2(S0.3Se0.7)3 nanoflakes for photo electrochemical cell application” J. Mater. Sci. Mater. Electronics, 29 (2018) 9142. (I.F. 2.77).
Sanjay Sahare, Prachi Ghoderao, Abhijeet Dey, Suwarna Datar, and Tejashree Bhave, “Study of modification of photo active material with carbon nanostructures for polymer solar cell applications” Mater. Today Comm., 12 (2017) 11. (I.F. 3.66).
Sanjay Sahare, Prachi Ghoderao, Naresh Veldurthi, Deepak Mishra, Tejashree Bhave, "Optical fiber sensor based on hybrid material: Comparative study of theoretical model and fabricated sensor," 2nd International Symposium on Physics and Technology of Sensors (ISPTS), 2015, 209, doi: 10.1109/ISPTS.2015.7220114
Prachi Ghoderao, Sanjay Sahare, Anjali A. Kulkarni, Tejashree Bhave,“Paclitaxel conjugated magnetic carbon nanotubes induce apoptosis in breast cancer cells and breast cancer stem cells in vitro” Paclitaxel, Elsevier (2022) 309-331.
Prachi Ghoderao, Sonali Sanghavi, Tejashree Bhave and Anjali A. Kulkarni” Drug Coated Nanoparticles: The Magic Bullets for Threatening Diseases with Special Reference to Tuberculosis” Materials for Biomedical Engineering Nanomaterials-Based Drug Delivery, Elsevier (2019) 41-85.
Sanjay Sahare, Manjeet Kumar, Prachi Ghoderao, A. Radhamanohar, S-L Lee and J-H Yun, “Oxide perovskites and their derivatives for photovoltaic applications." Advanced Ceramics for Energy and Environmental Applications, pp. 216-230, CRC press, 2021