Slow-targeted release of a ruthenium anticancer agent from vitamin B₁₂functionalized marine diatom microalgae

Abstract

Bio-inspired drug capsules: The synthesis of a new vitamin-B12 modified biomaterial with increased static adherence properties toward cancer cell lines, allowed the targeted delivery of a poorly water-soluble ruthenium drug with an unprecedented release profile.

Photoactivatable Surface-Functionalized Diatom Microalgae for Colorectal Cancer Targeted Delivery and Enhanced Cytotoxicity of Anticancer Complexes

“…For the Mn-DEMs (synthetized to assess the feasibility of the surface coating), a peak at 431 corresponding to the MLCT absorbance spectrum of the Mn complex is detected. In the case of B12-DEMs[25], peaks at 361 nm, 521 nm and 545 nm are consistent with absorbance of pure cyanocobalamin[70]. Finally, the spectrum of B12-Mn-DEMs shows peaks corresponding to cobalamin at 363 nm, 515 nm and 545 nm as well as a very small peak at 423 nm attributed to the presence of Mn.…”

“…We have recently began to develop CFDD materials based on environmentally sustainable, abundant and inexpensive diatom microalgae (DEMs) [24] with the aim of designing an innovative structure able to simultaneously target the tumor site and release loaded chemotherapeutics in its immediate proximity [25]. DEMs, as the fossil frustules of diatoms, recently gained attention for their use in drug delivery due to their biocompatibility and ability to shuttle and slowly release different drugs [26][27][28][29].…”

“…Alternatively B12-ZnTCPP could be prepared by PEGylation of TCPP followed by metalation and coupling to vitamin B12. We note here that the length of the selected PEG-chain allows vitamin B12 derivatives to be still recognized by the transcobalamin receptors (TC(II) and TC(II)-R) leading to increased adherence towards cancer cells[25,59,60]. DFT calculations of B12-Mn and B12-TCPP performed in water (polarizable continuum model, vide infraFigure 2) indicate a distance of ca.…”

“…The molecules were successfully loaded into DEMs according to the vacuum infiltration method described by Vasani et al[79] (giving 1@B12-ZnTCPP-DEMs and 2@B12-Mn-DEMs respectively) with respective loading degrees of 3.7 (1) and 1.5 (2) wt% (Table 2). These are in the typical range of drugs loaded into DEMs biosilicas[25,26,[80][81][82]. Following successful encapsulation, the drug release in PBS buffer pH 7.4 (1 % v/v, DMSO), was initiated by addition of solvent and monitored by UV-VIS spectroscopy over period of 5 days in both cases.…”

Evaluation of the Potential of Cobalamin Derivatives Bearing Ru(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy

“…[20] This interesting characteristic was already used in several studies [21] in which cobalamin was employed as a targeting moiety for metal complexes to direct them towards fast dividing malignant cells. [22][23][24] With this in mind, in this work, we aimed at developing a system for improving the solubility and uptake of Ru(II)-based PSs into cancer cells. Our hope was that the resulting conjugates would have a good water solubility and an active cellular uptake.…”