Loading of Cisplatin into Mesoporous Silica Nanoparticles: Effect of Surface Functionalization

Abstract

Cisplatin (CDDP) plays a crucial role in the treatment of various malignant tumors. However, its clinical efficacy and applicability are restricted by issues of toxicity and resistance. Here, for drug delivery purposes, the outer surface of MCM-41 silica nanoparticles (MSNs) were functionalized with polyethylene glycol (PEG, M w = 10,000 g/mol) or low molecular weight (M w = 1,800 g/mol) branched polyethyleneimine (PEI). Given the strong affinity of sulfur for platinum, thiol-functionalized MSNs were synthesized for comparison by co-condensation with (3-mercaptopropyl)triethoxysilane (MPTES). CDDP loading was performed either by adsorption or impregnation in aqueous media without the use of dimethylsulfoxide (DMSO) as a solubilizer. CDDP loading capacities obtained by impregnation were higher than those obtained by adsorption and varied from 3.9 to 16.1 wt%, depending on the functional group. Loaded nanomaterials were characterized by SEM, STEM-HAADF and Raman spectroscopy. Depending upon the functional groups, platinum-based species were either dispersed in the nanomaterials as nanocrystals or uniformly distributed as molecular species. The spectral signature of CDDP was strongly modified when platinum species were homogeneously distributed within the nanomaterials. Preliminary drug release studies performed at 37°C showed that the behavior of the CDDP loaded MSNs strongly depends on the nature of the present functional groups. Among the functionalization routes investigated in this paper, PEI-based functionalization showed the most promising results for further applications in controlled drug release with an absence of burst release and a sustained release over 72 h.

Mesoporous Silica Particles as Drug Delivery Systems—The State of the Art in Loading Methods and the Recent Progress in Analytical Techniques for Monitoring These Processes

“…Similar relationships were shown in the study of the mesoporous SBA-15 surface loaded with vanadium [ 221 ]. The much higher sensitivity of Raman spectroscopy compared to IR for groups such as the thiol group made this spectroscopy the basis for determining the cisplatin loading of mesoporous silica modified with SH groups [ 222 ]. Bouyer et al observed vibration bands of tetracyclosiloxane rings—486 cm −1 , symmetric stretching bands from the Si–O–Si group—800 cm −1 , and vibrations related to the stretching mode of Si–OH hydroxyl surfaces—978 cm −1 for both MSN–SH and MSN.…”

“…For example, to determine the crystalline structure of the magnetic nanoparticles before and after silica coating [ 228 ], or to confirm the presence of iron oxide and identify the relative crystalline phases formed in the synthesis of polymer grafted MSNs [ 229 ]. Further cases show the loading of indomethacin in an amorphous phase [ 230 ], and characterization of the mercapto-functionalized MCM-41 proving their stability after the modification process [ 222 ]. Importantly, one has to realize that the data provided by XRD experiments arises from the structural properties of crystal domains and not necessarily from the entire particle.…”

Silica Nanoparticles in Transmucosal Drug Delivery

“…However, non-functionalised MCM-41 showed a rapid aspirin release [52]. Many other publications have reported the feasibility of plain and functionalised silica nanoparticles in controlled drug delivery [53][54][55].…”

<p>Core–Shell Imidazoline–Functionalized Mesoporous Silica Superparamagnetic Hybrid Nanoparticles as a Potential Theranostic Agent for Controlled Delivery of Platinum(II) Compound</p>

“…Also, different types of inorganic nanoparticles have been used for Cis-Pt delivery, including gold nanoparticles, 10 metal-organic frameworks, 11 and porous and nonporous silica nanoparticles. 12 Due to their unique properties, such as magnetic susceptibility, biocompatibility and ability to modify surface functionalization, 13 iron oxide magnetite nanoparticles are of great interest for various biomedical applications, including usage in magnetic hyperthermia, 14 magnetic resonance imaging (MRI), 15 photoacoustic imaging, 16 photodynamic therapy, 17,18 photo-thermal therapy, 19 biological detection, 20 magnetic bio-separation, 21 etc. Magnetic iron oxide nanoparticles can reduce transverse relaxation time, known as T 2 , by producing an inhomogeneous magnetic field around the outer shell, which results in negative MR images.…”