Abstract
This contribution reports the design, preparation, photophysical and photochemical characterization, as well as a preliminary biological evaluation of mesoporous silica nanoparticles (MSNs) covalently integrating a nitric oxide (NO) photodonor (NOPD) and a singlet oxygen (1O2) photosensitizer (PS) and encapsulating the anticancer doxorubicin (DOX) in a noncovalent fashion. These MSNs bind the NOPD mainly in their inner part and the PS in their outer part in order to judiciously exploit the different diffusion radius of the cytotoxic NO and 1O2. Furthermore this silica nanoconstruct has been devised in such a way to permit the selective excitation of the NOPD and the PS with light sources of different energy in the visible window. We demonstrate that the individual photochemical performances of the photoactive components of the MSNs are not mutually affected, and remain unaltered even in the presence of DOX. As a result, the complete nanoconstruct is able to deliver NO and 1O2 under blue and green light, respectively, and to release DOX under physiological conditions. Preliminary biological results performed using A375 cancer cells show a good tolerability of the functionalized MSNs in the dark and a potentiated activity of DOX upon irradiation, due to the effect of the NO photoreleased.
Highlights
Multimodal cancer therapy involves the use of two or more treatment modalities with the aim to attack tumors on different sides by acting either on a single oncogenic pathway through different mechanisms or across parallel pathways without amplification of side effects [1,2,3,4]
We have designed, synthesized and characterized a novel “three bullet” nanoconstruct based on mesoporous silica nanoparticles for potential combined cancer photo-chemotherapy
PS-mesoporous silica nanoparticles (MSNs)-NO photodonors (NOPD)/DOX reduced cell viability more than PS-Modified MSNs (PS-MSNs)-NOPD and PS-MSNs/DOX, suggesting that the presence of NOPD enhances the efficacy of DOX
Summary
Multimodal cancer therapy involves the use of two or more treatment modalities with the aim to attack tumors on different sides by acting either on a single oncogenic pathway through different mechanisms or across parallel pathways without amplification of side effects [1,2,3,4]. Among the light-activatable therapeutic treatments, photodynamic therapy (PDT) is so far one of the most promising to combat cancer diseases [7] This treatment modality mainly exploits the cytotoxic effects of the highly reactive singlet oxygen (1O2), catalytically generated by energy transfer between the long-lived excited triplet state of a photosensitizer (PS) and the nearby molecular oxygen [8]. Mesoporous silica nanoparticles (MSNs) are very suitable scaffolds to this end due to their high loading capacity, ease of surface functionalization, good biocompatibility, and satisfactory light transparency [26,27,28,29,30] These inorganic scaffolds have been extensively used as excellent carrier for (i) conventional chemotherapeutics to reverse MDR [31], (ii) PDT agents alone and in combinations with chemotherapeutics [32,33,34], and (iii) spontaneous NO donors [35] and NOPD [36]. The spontaneous release of DOX under physiological conditions can be combined with the photoregulated generation of 1O2, NO, or both by using light stimuli of appropriate energy in the visible light range
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