Abstract
1) The paper discusses the limitations of traditional oral anticancer drugs, such as poor stability in aqueous solutions and nonspecific targeting, and proposes the use of nanocarriers to overcome these issues.
2) The study introduces a series of nine covalent organic frameworks (COFs) as drug delivery nanocarriers, with COF-3 showing the highest efficacy against ovarian cancer cells when loaded with paclitaxel.
3) The work highlights the potential of COFs in therapeutic drug delivery due to their biocompatibility and controlled drug release capabilities, offering a new avenue in sarcoma therapy.

Background
1) Industry Problems: The high morbidity and mortality rates of cancer, particularly ovarian cancer, pose a significant public health challenge. Treatments like chemotherapy and surgery face the threat of therapy-resistant metastasis.
2) Scholarly Solutions: Researchers have proposed various drug delivery agents, including COFs, to improve treatment efficacy and reduce side effects.
3) Innovative Ideas by Authors: The authors propose the use of COFs as drug carriers for paclitaxel, focusing on the epithelial–mesenchymal transition (EMT) of ovarian cancer cells, which play a crucial role in metastasis.

Experimental Details
1) Synthesis of COFs: Nine COFs were synthesized using Schiff base reactions between different hydroxy-containing trialdehyde and triamine moieties.
2) Characterization of COFs: The COFs were characterized using FTIR, PXRD, solid-state 13C NMR, TGA, and N2 sorption measurements to confirm their structure, crystallinity, and porosity.
3) Drug Loading and Cytotoxicity Testing: Paclitaxel was loaded onto the COFs, and the cytotoxic effects of PTX-loaded COFs were tested on SKOV-3 cells, with COF-3 showing the most potent results.

Test and Analysis
1) Morphological Analysis: Cells treated with PTX+COF-3 showed abnormal cellular morphology and fragmented nuclei, indicating the inhibitory effect on cell proliferation.
2) Cell Migration and Colony Formation: PTX+COF-3 treatment resulted in a significant decrease in cell migration and colony formation, suggesting its potential in inhibiting metastasis.
3) Expression of EMT Markers: Flow cytometry analysis showed an increase in E-cad expression and a decrease in N-cad expression in PTX+COF-3 treated cells, indicating a reversal of EMT.

Conclusion
1) Nine COFs were successfully synthesized and characterized, demonstrating their potential as drug delivery agents.
PTX+COF-3 was found to be more effective in inhibiting ovarian cancer cell proliferation and metastasis than the drug alone.
2) The study opens new opportunities for COFs in targeted cancer therapy, with potential for further exploration in sarcoma treatment.
3) The long-term stability and scalability of COFs for drug delivery in clinical settings need further investigation.
Shortcomings: The study lacks in-depth mechanistic insights into how COFs enhance drug efficacy and the exact role of COF-3 in EMT regulation.


Covalent Organic Frameworks as Potential Drug Carriers and Chemotherapeutic Agents for Ovarian Cancers
Atikur Hassan, Sraddhya Roy, Ananya Das, Sk Abdul Wahed, Aparajita Bairagi, Subhadip Mondal, Nabanita Chatterjee*, and Neeladri Das*
DOI: 10.1021/acsbiomaterials.4c00351
Link: https://pubs.acs.org/doi/10.1021/acsbiomaterials.4c00351