Abstract
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.
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The authors gratefully acknowledge the support of this work by Iran University of Science and Technology and Motamed Cancer Institute.
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Detailed description on procedures, DOX loading in Cu-TCPP MOF and CuG nanocomposites, and further characterizations, including PXRD pattern of GO, Elemental mapping of CuG1, zeta potential results for the Cu-TCPP MOF, CuG1 and CuG1-DOX, several mathematical models (Higuchi, zero order, first order and Korsmeyer–Peppas) and different kinetics parameters of DOX release from CuG1, Kinetics of DOX release from CuG1, in vitro DOX release of the Cu-TCPP MOF-DOX and CuG1-DOX at various pH with additional microscopic images are presented in supporting information (PDF 2068 KB)
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Gharehdaghi, Z., Rahimi, R., Naghib, S.M. et al. Cu (II)-porphyrin metal–organic framework/graphene oxide: synthesis, characterization, and application as a pH-responsive drug carrier for breast cancer treatment. J Biol Inorg Chem 26, 689–704 (2021). https://doi.org/10.1007/s00775-021-01887-3
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DOI: https://doi.org/10.1007/s00775-021-01887-3