Doxorubicin bioavailability to human hemoglobin and cancer cells via MOF-A520

• Published in: Journal of molecular liquids 2024-01, Vol.394, p.123724, Article 123724
• Main Authors: Edrisi, Mohammad, Daneshgar, Hossein, Rabiee, Navid, Arghavani, Payam, Moosavi-Movahedi, Faezeh, Zare Karizak, Ashkan, Khatibi, Ali, Hong, Jun, Bagherzadeh, Mojtaba, Moosavi-Movahedi, Ali A.
• Format: Article
• Language: English
• Subjects: Doxorubicin; Drug delivery system; Drug-Hemoglobin interaction; Metal-organic frameworks (MOFs); Toxicity
• ISSN: 0167-7322; 1873-3166
• DOI: 10.1016/j.molliq.2023.123724

[Display omitted] •The manuscript explains why doxorubicin (DOX) should be held by A520 as a metal–organic framework (MOF).•A520 was synthesized using green chemistry methods, which can destruct into biodegradable compounds during physical conditions.•Achievements include synthesis and characterization of A520, loading of DOX onto A520, observation of drug releasing rate, study of interactions of DOX with hemoglobin, bioavailability of DOX by A520 for controlling toxicity and reduction of side effects in molecular (human hemoglobin) and cellular approaches (cancer and normal cell lines).. Cancer is one of the most serious and challenging issues in the life sciences, with complicated and multifactorial mechanisms making it difficult to manage. With this complexity comes various strategies for attacking tumors, including using nanomaterials to target tumor cells, bioavailability and deliver anticancer drugs directly. Doxorubicin (DOX) is a well-known and powerful anticancer drug, but its high toxicity limits its application. Intending to reduce the cytotoxic effects of DOX on normal cell line and deliver it to cancerous cell line, the present study attempts to design and synthesize a modified metal–organic framework (MOF) named A520 and a composite containing DOX (A520@DOX). The synthesized MOFs were characterized using X-ray diffraction (XRD), electron microscopy (TEM and FESEM), and FTIR. Subsequently, the toxicity of DOX was assessed at the cellular and molecular levels using MTT assays (for the cell lines MCF −10A and MCF-7) and various biophysical assays targeting human hemoglobin (Hb). Following expectations, free DOX was highly cytotoxic and strongly affected Hb structure (converting it into methemoglobin species), while the toxicity was significantly reduced in the A520@DOX composite form. It is important to mention that DOX released from the A520@DOX was significantly pH-sensitive, so it was more pronounced in acidic pH 5 (resembling a cancerous pH environment). Furthermore, the effect of DOX released from A520@DOX resulted in more oxyHb and deoxyHb species as functional Hb species. The present study used an effective DOX delivery and bioavailability nanosystem to control cytotoxicity and ensure slow drug release.