Cu (II)-porphyrin metal–organic framework/graphene oxide: synthesis, characterization, and application as a pH-responsive drug carrier for breast cancer treatment

• Published in: Journal of biological inorganic chemistry Vol. 26; no. 6; pp. 689 - 704
• Main Authors: Gharehdaghi, Zahra, Rahimi, Rahmatollah, Naghib, Seyed Morteza, Molaabasi, Fatemeh
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.09.2021; Springer Nature B.V
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Biochemistry; Biodegradation; Biomedical and Life Sciences; Breast cancer; Breast Neoplasms - drug therapy; Cancer therapies; Chemotherapy; Controlled release; Copper; Copper - chemistry; Cytotoxicity; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - therapeutic use; Drug Carriers - chemical synthesis; Drug delivery; Drug Delivery Systems; Drug Design; Drug Liberation; Female; Graphene; Graphite - chemistry; Humans; Hydrogen-Ion Concentration; Life Sciences; Low temperature; MCF-7 Cells; Metal-Organic Frameworks - chemistry; Mice; Mice, Inbred BALB C; Microbiology; Models, Molecular; Molecular Structure; Nanocomposites; Original Paper; pH effects; Porosity; Porphyrins; Porphyrins - chemistry; Xenograft Model Antitumor Assays; Metal–organic framework; Graphene oxide; Nanocomposite; Porphyrin; pH-responsively doxorubicin release; Controlled release
• ISSN: 0949-8257; 1432-1327
• DOI: 10.1007/s00775-021-01887-3

A new multifunctional graphene oxide/Cu (II)-porphyrin MOF nanocomposite (CuG) comprised of Cu-TCPP MOF supported on graphene oxide (GO) nanosheets, has been fabricated by a solvothermal method at low temperature and one-pot process. Cu-TCPP MOF with universal advantages, such as high porosity, nontoxicity, large surface area, and safe biodegradation, combined with GO allows the achievement of an efficient doxorubicin loading (45.7%) and smart pH-responsive release for chemotherapy. More significantly, more than 97% of DOX was released by CuG at pH 5 which was more than that at pH 7.4 (~ 33.5%), while Cu-TCPP MOF displayed DOX release of 68.5% and 49% at pH 5 and 7.4, respectively , illustrating the effect of GO on the smart MOF construction for controllable releasing behavior in vitro . The results of in vitro anticancer experiments demonstrate that the developed nanocarrier exhibited slight or no cytotoxicity on normal cells, while the drug-loaded nanocarrier increased significant cancer cell-killing ability with higher therapeutic efficacy than free DOX, indicating the sustained release behavior of the CuG nanocarrier without any “burst effect”. Moreover, the in vivo experiments demonstrated that the CuG-DOX exhibited significantly higher anticancer efficiency compared with free DOX. High anti-cancer therapeutic efficacy of this nanoscale carrier as an efficient pH sensitive agent, has the potential to enter further biomedical investigations. Graphic abstract A new smart multifunctional graphene oxide–Cu (II)-porphyrin MOF nanocomposite (CuG) formed of Cu-TCPP MOF and graphene oxide (GO) has successfully fabricated and demonstrated an efficient pH-responsive drug release behavior in cancer therapy without using any targeting ligand.