Talks
Design and optimization of biomimetic supramolecular nanoconstruct for effective targeting and therapy for triple negative breast cancer
Academic/Professional Position (Other)
PhD
Presentation Type
Oral Presentation
Discipline Track
Clinical Science
Abstract Type
Research/Clinical
Abstract
Background: Breast cancer is the second most diagnosed cancer among American women. Although there are some significant improvements in survival, therapies have been met for some subtypes of breast cancer, yet not much improvement is achieved for triple negative breast cancer. Thus, conventional therapies as chemotherapy by systemic route are the most used treatment regimens by clinicians. Although, these therapies effective in subsiding cancer at the time being yet causes significant adverse aftereffects and/or relapse of the cancer because of the administration of the cytotoxic chemotherapeutic agents.
Materials & methods: Supramolecular nanoconstructs were designed by PVP and TA loaded with paclitaxel and coated with LPS activated bio-inspired artificial cell membranes or naturally derived cell membranes. Using homogenization and differential centrifugation techniques the membrane coated nanoparticles were generated. They were optimized and evaluated for optimum size, shape and with necessary functional moieties for effective targeting ability to the tumor cells. In vitro and vivo characterization was conducted to confirm the effectiveness of these nanoconstruct. Additionally, safety evaluation was conducted by processing the histopathology, blood chemistry analysis and hemotoxicity images.
Results: Overall we have tested five bioinspired cell membranes. Among these we conclude that the neutrophil coated nanoparticles possess the best targeting ability by prolonging circulation for at least 24-48hrsin comparison to non-membrane coated nanoparticles that were cleared within 6-8hrs. The safety evaluation was the most significant finding in this study, which suggests the membrane coated nanoparticles improved the respective serum enzyme and blood count levels in comparison to the other treatment groups. Thus, concluding that these nanoparticles were comparatively safer therapeutic option for preventing common adverse effects such as leukopenia and neutropenia and severe peripheral neurotoxicity seen in 30-40% of patients receiving chemotherapy by paclitaxel.
Conclusion: This study represents a safer therapeutic potential of cell membrane-based nanoparticle constructs that not only provides enhanced targeting to the tumor regions and metastatic microenvironment due to self-marker recognition on their surface. But also, the safety profile generated from this finding is a significant contribution to the patient community administrating paclitaxel as their primary treatment modality, as the side effects caused for the systemic administration of paclitaxel and similar chemotherapeutics cause some serious adverse effects that affects their quality of their life. All of which could be mitigated with developing similar therapeutic options as membrane-based nanoparticles.
Recommended Citation
Chowdhury, Pallabita; Nagesh, Prashanth K.B.; Hatami, Elham; Jaggi, Meena; Chuahan, Subhash C.; and Yallapu, Murali M., "Design and optimization of biomimetic supramolecular nanoconstruct for effective targeting and therapy for triple negative breast cancer" (2023). Research Symposium. 52.
https://scholarworks.utrgv.edu/somrs/theme1/track1/52
Design and optimization of biomimetic supramolecular nanoconstruct for effective targeting and therapy for triple negative breast cancer
Background: Breast cancer is the second most diagnosed cancer among American women. Although there are some significant improvements in survival, therapies have been met for some subtypes of breast cancer, yet not much improvement is achieved for triple negative breast cancer. Thus, conventional therapies as chemotherapy by systemic route are the most used treatment regimens by clinicians. Although, these therapies effective in subsiding cancer at the time being yet causes significant adverse aftereffects and/or relapse of the cancer because of the administration of the cytotoxic chemotherapeutic agents.
Materials & methods: Supramolecular nanoconstructs were designed by PVP and TA loaded with paclitaxel and coated with LPS activated bio-inspired artificial cell membranes or naturally derived cell membranes. Using homogenization and differential centrifugation techniques the membrane coated nanoparticles were generated. They were optimized and evaluated for optimum size, shape and with necessary functional moieties for effective targeting ability to the tumor cells. In vitro and vivo characterization was conducted to confirm the effectiveness of these nanoconstruct. Additionally, safety evaluation was conducted by processing the histopathology, blood chemistry analysis and hemotoxicity images.
Results: Overall we have tested five bioinspired cell membranes. Among these we conclude that the neutrophil coated nanoparticles possess the best targeting ability by prolonging circulation for at least 24-48hrsin comparison to non-membrane coated nanoparticles that were cleared within 6-8hrs. The safety evaluation was the most significant finding in this study, which suggests the membrane coated nanoparticles improved the respective serum enzyme and blood count levels in comparison to the other treatment groups. Thus, concluding that these nanoparticles were comparatively safer therapeutic option for preventing common adverse effects such as leukopenia and neutropenia and severe peripheral neurotoxicity seen in 30-40% of patients receiving chemotherapy by paclitaxel.
Conclusion: This study represents a safer therapeutic potential of cell membrane-based nanoparticle constructs that not only provides enhanced targeting to the tumor regions and metastatic microenvironment due to self-marker recognition on their surface. But also, the safety profile generated from this finding is a significant contribution to the patient community administrating paclitaxel as their primary treatment modality, as the side effects caused for the systemic administration of paclitaxel and similar chemotherapeutics cause some serious adverse effects that affects their quality of their life. All of which could be mitigated with developing similar therapeutic options as membrane-based nanoparticles.