Project Title

Folic Acid-Carbon Dots-Doxorubicin (FA-CD-DOX) Nanoparticles as Cancer Theranostic

Authors' Affiliations

Michael Tetteh, Department of Chemistry, College of Arts and Sciences, East Tennessee State University, Johnson City, TN Dr. Hua Mei, Department of Chemistry, College of Arts and Sciences, East Tennessee State University, Johnson City, TN

Location

Culp Room 303

Start Date

4-6-2022 1:00 PM

End Date

4-6-2022 2:00 PM

Faculty Sponsor’s Department

Chemistry

Name of Project's Faculty Sponsor

Hua Mei

Additional Sponsors

Dr. Catherine McCusker Dr. Aleksey Vasiliev

Classification of First Author

Graduate Student-Master’s

Competition Type

Competitive

Type

Oral Presentation

Project's Category

Analytical Chemistry, Biochemistry, Organic Chemistry, Cancer or Carcinogenesis

Abstract or Artist's Statement

Despite the recent advances in cancer therapy, the successful detections and treatments of cancer still remains a challenge. The existing strategies for early cancer detection are often limited due to their poor sensitivity and specificity. Also, the non-selective action of therapeutic interventions hinders treatment success. Our research was therefore directed towards the engineering of excellent bi-functionalized nanoparticles (NPs) based on carbon dots (CDs) that would improve early cancer detection and overcome the limitations of chemotherapy. With the actively targeting agent, these new NPs are expected to effectively deliver pharmacological agents directly to cancer cells. CDs are carbon-based NPs that are utilized as bioimaging agents and drug delivery systems (DDS) due to their excellent biocompatibility, non-toxicity, unique imaging, and facile surface modification. Using folic acid (FA) as targeting agent, the prepared novel CDs will carry doxorubicin (DOX) covalently and non-covalently to the cancer cells with overexpressed folate receptors. The CDs were first synthesized via the hydrothermal bottom-up approach using citric acid and ethylenediamine as precursors. The prepared CDs were then functionalized by FA via a non-cleavable peptide bond followed by complexation with DOX covalently or non-covalently to obtain the desired FA-CD-DOX NPs. All the NPs and intermediates were characterized using ultraviolet-visible spectroscopy (UV-vis), fluorescence spectroscopy (FL), and Fourier transform infrared spectroscopy (FTIR). Assessment of the drug loading capacity (DLC) and drug loading efficiency (DLE) with UV-vis indicated that the non-covalent NPs have low DLC but high DLE compared to the relatively low DLE and high DLC of covalent NPs. In vitro drug release studies were also carried out in phosphate buffered saline (PBS) systems with various pH. It was found that even though both non-covalent and covalent complexes released more DOX at pH 5.0 than at pH 7.0, the DOX release rate was faster in the non-covalent FA-CD-DOX NPs compared to the covalent FA-CD-DOX. Based on these results, we project increased accumulation of drugs in the more acidic (pH 4.5-5.0) microenvironment of cancer cells compared to that of normal healthy cells under physiological pH (7.4). This new FA-CD-DOX NPs could work as efficient theranostic systems to detect and treat cancer.

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Apr 6th, 1:00 PM Apr 6th, 2:00 PM

Folic Acid-Carbon Dots-Doxorubicin (FA-CD-DOX) Nanoparticles as Cancer Theranostic

Culp Room 303

Despite the recent advances in cancer therapy, the successful detections and treatments of cancer still remains a challenge. The existing strategies for early cancer detection are often limited due to their poor sensitivity and specificity. Also, the non-selective action of therapeutic interventions hinders treatment success. Our research was therefore directed towards the engineering of excellent bi-functionalized nanoparticles (NPs) based on carbon dots (CDs) that would improve early cancer detection and overcome the limitations of chemotherapy. With the actively targeting agent, these new NPs are expected to effectively deliver pharmacological agents directly to cancer cells. CDs are carbon-based NPs that are utilized as bioimaging agents and drug delivery systems (DDS) due to their excellent biocompatibility, non-toxicity, unique imaging, and facile surface modification. Using folic acid (FA) as targeting agent, the prepared novel CDs will carry doxorubicin (DOX) covalently and non-covalently to the cancer cells with overexpressed folate receptors. The CDs were first synthesized via the hydrothermal bottom-up approach using citric acid and ethylenediamine as precursors. The prepared CDs were then functionalized by FA via a non-cleavable peptide bond followed by complexation with DOX covalently or non-covalently to obtain the desired FA-CD-DOX NPs. All the NPs and intermediates were characterized using ultraviolet-visible spectroscopy (UV-vis), fluorescence spectroscopy (FL), and Fourier transform infrared spectroscopy (FTIR). Assessment of the drug loading capacity (DLC) and drug loading efficiency (DLE) with UV-vis indicated that the non-covalent NPs have low DLC but high DLE compared to the relatively low DLE and high DLC of covalent NPs. In vitro drug release studies were also carried out in phosphate buffered saline (PBS) systems with various pH. It was found that even though both non-covalent and covalent complexes released more DOX at pH 5.0 than at pH 7.0, the DOX release rate was faster in the non-covalent FA-CD-DOX NPs compared to the covalent FA-CD-DOX. Based on these results, we project increased accumulation of drugs in the more acidic (pH 4.5-5.0) microenvironment of cancer cells compared to that of normal healthy cells under physiological pH (7.4). This new FA-CD-DOX NPs could work as efficient theranostic systems to detect and treat cancer.