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Engineered transferrin-conjugated PEGylated multifunctional MOF-74 as precision nanotheranostics for triple-negative
Sanjay Kulkarni1, Soji Soman1, Abhijeet Pandey2
1Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
Abstract:
This study details the development and evaluation of a zinc-based MOF (MOF-74) for targeted cancer therapy. Doxorubicin (DOX) was selected as the active pharmaceutical ingredient because of its well-established efficacy against cancer. Preformulation studies were conducted to identify, and characterise DOX, and to establish quantitative methods for its estimation. MOF-74 was synthesised via precipitation and loaded with DOX via postsynthesis diffusion, ensuring optimal drug loading. To enhance the pharmacokinetic profile of DOX, the MOFs were PEGylated and further conjugated with a transferrin ligand to achieve efficient tumour targeting. This leverages transferrin receptors overexpressed on cancer cells to direct the surface-modified MOFs to the tumour site. The synthesised MOFs were characterised by spectroscopic analysis, morphological studies, and assessments of their thermal stability. The in vitro drug release profile was studied alongside evaluations of the toxicological aspects, ensuring the safety and effectiveness of the formulation. Different studies have examined the anticancer efficacy of DOX-loaded MOFs. Overall, it offers a promising approach to address the challenges associated with traditional chemotherapy, such as nonspecific toxicity and limited efficacy. By PEGylating the MOF and conjugating it with transferrin, the formulation minimises off-target effects and ensures precise delivery of DOX to the tumour, thereby enhancing the overall therapeutic outcome.

