Amino-Functionalized Mesoporous Silica Nanoparticle-Encapsulated Octahedral Organoruthenium Complex as an Efficient Platform for Combatting Cancer

Abstract

In the process of synthesis of a new drug, as important as the drug itself is the formulation used, because the same compound can present a very different efficacy depending on how it is administered. In this work, we demonstrate how the antitumor capacity of a new octahedral organoruthenium complex, [Ru(ppy-CHO)(phen) 2 ][PF 6 ] is affected by its encapsulation in different types of mesoporous silica nanoparticles. The interactions between the Ru complex and the silica matrix and how these interactions are affected at two different pHs (7.4 and 5.4, mimicking physiological and endolysosomal acidic conditions, respectively) have been studied. The encapsulation has also been shown to affect the induction of apoptosis and necrosis and progression of the cell cycle compared to the free drug. The encapsulation of the Ru complex in nanoparticles functionalized with amino groups produced very high anticancer activity in cancer cells in vitro, especially against U87 glioblastoma cells, favoring cellular internalization and significantly increasing the anticancer capacity of the initial non-encapsulated Ru complex. 47 example, the ruthenium(III) complex NKP-1339 is undergoing 48 clinical trials for cancer treatment, 11 and Ru II (η 6 -arene) 49 complexes have been investigated for their tunability and 50 novel modes of action. 12−15 The combination of polypyridyl 51 ruthenium drugs with nanoscale drug delivery systems has 52 garnered a great deal of research attention. 16,17 Compared with 53 the planar structure of platinum drugs, the octahedral 54 configuration of ruthenium complexes provides a rigid 55 framework for the construction of a nanocarrier and their 56 planar ligands may provide hydrophobic cavities for drug 57 loading. 18 However, many Ru complexes have limited capacity 58 to cross the cell membrane. 19,20 59 Mesoporous silica nanoparticles (MSNs) have unique 60 properties such as a large surface area, high stability and 61 degree of tunability, and good biocompatibility, making them 62 excellent vehicles for the delivery of any type of drug, especially 63 one with antitumor purposes. 21 Other materials widely used in 64 drug delivery are liposomes and polymeric nanoparticles. 65 Unlike the first ones with low stability or the second ones

Nanoantibiotics Based in Mesoporous Silica Nanoparticles: New Formulations for Bacterial Infection Treatment

“…Professor María Vallet-Regí's research group has widespread experience in stimulusresponse nanosystems based on MSNs in the treatment of several types of cancer cells, with numerous studies associated with the application of different internal and external stimuli in this area [25,28,30]. Specifically, this group has developed studies with nanosystems based on MSNs related to internal stimulus-response such as pH [150][151][152][153] or redox processes [154], and the application of several external stimuli as ultrasounds [155][156][157][158], magnetic field [159,160], photothermal therapy [161] or visible light [162]. In addition, the combination of therapeutic approaches has been proven as a complementary approach for conventional chemotherapy.…”

Surface structure of linear nanopores in amorphous silica: Comparison of properties for different pore generation algorithms

“…However, it is also appropriate to note that neither of these methods attempt to mimic the complexity of the commonly used solution-phase synthesis of mesoporous silica via a soft-templating approach. 10 They also do not capture the time scale of such synthesis processes, e.g., on the order of 2 h for recent syntheses of MCM-41 by the Ames group 17,43,44 and by many other groups, [45][46][47] but on the order of days for earlier syntheses. 48 Nonetheless, these models have been deemed to be useful for the study of, e.g., confined fluids, a key requirement being a realistic description of the surface chemistry of the pores.…”

pH-Responsive Release of Ruthenium Metallotherapeutics from Mesoporous Silica-Based Nanocarriers

“…Part of the research community is investigating the potential of nanomaterials for loading and delivering Ru complexes [ 36 ], as well as their influence on drug activity [ 37 ]. Mesoporous Si-based nanoparticles containing covalently linked Ru(II) complexes have been examined for photodynamic therapy of cancer [ 38 , 39 ], construction of photo-responsive drug delivery systems [ 40 , 41 ] and cancer-targeted therapy based on pore-loaded Ru(II) metallotherapeutics [ 42 , 43 ]. MSN-based nanocarriers for pH-responsive release of metal-based drugs have been also studied.…”

“…For example, Lv et al utilized MSN coated with a biotin-chitosan conjugate for pH-sensitive release of a Ru(II) N-heterocyclic carbene complex, which occurs due to a conformational change of chitosan molecule [ 44 ]. Encapsulation and pH-responsive release of C,N-cyclometalated organoruthenium complex from amino-functionalized MSN was shown to enhance its effectiveness against glioblastoma multiforme cells [ 42 ], while pH-responsive release of Ru(II) polypyridyl complexes from RGD-functionalized MSN have been demonstrated to enhance cancer apoptosis [ 45 ]. Aminopropyl-functionalized MSN were also demonstrated to enhance the stability of quercetin and improve its penetration into the skin for topical therapy of JR8 melanoma cells [ 46 ].…”