Chapter Five - Light-triggered unconventional therapies with engineered inorganic nanoparticles
Introduction
Inorganic nanoparticles (NPs), including nonporous and mesoporous silica NPs, carbon-based NPs, quantum dots, and noble metal-based plasmonic NPs, display a wealth of structural and optical properties. These materials provide intriguing building blocks for the realization of functional nanomaterials with great prospects in diagnostic, therapeutic and theranostic applications.1, 2, 3, 4, 5, 6, 7 In this frame, the achievement of NPs addressed to the release of therapeutics with precise spatiotemporal control is one of the most active areas.8, 9, 10, 11 Site, timing and dosage of such release play key roles in determining the efficacy of the therapeutic outcome.
The fast rates of the photochemical processes, many of which occur in the ns and ps time regime, and the easy manipulation of photons in terms of energy, intensity, location, and duration, make light, a powerful and minimally invasive trigger for the fine regulation of the release process with exquisite spatiotemporal control.12 Moreover, light does not affect physiological values of pH and temperature, essential criteria for biomedical applications.
The convergence of consolidated knowledges in molecular photochemistry and the significant breakthroughs in materials chemistry have led in recent years to a successful marriage between photo-science and nanomaterials science resulting in creative examples of photoactivatable NPs for therapeutic release.8, 9, 10, 11, 12 Two-photon excitation, by using femtosecond lasers,13 allows one to photoactivate many chromogenic centers in the so-called therapeutic window (650–1300 nm)14 with high penetrating near infrared (NIR) light. Besides, the parallel technological advances in fiber optic light-guides are considerably pushing photoactivatable nanomaterials towards less utopian applications, opening great prospects for an entirely new category of clinical solutions.
In the frame of NPs for light-activated therapy, those devoted to “unconventional” therapeutic approaches are very appealing. Photodynamic therapy (PDT),15 nitric oxide (NO) photodynamic therapy (NO-PDT)16 and photothermal therapy (PTT)17 play dominant roles in this context. These emerging treatment modalities exploit localized cytotoxic action induced by a “burst” of harmful species such as singlet oxygen (1O2), nitric oxide (NO) or heat, generated with superb spatiotemporal control by appropriate photoprecursors. Such strategic approaches hold a high degree of innovation to be used either as alternative to, or in combination with, conventional therapies based on chemotherapeutic and antibiotic drugs.
Fabrication of these photoresponsive NPs requires an appropriate design phase to obtain a specific response of the engineered NPs to light stimuli and interdisciplinary efforts, because of the synthetic procedures necessary to integrate the photoactive components into nanoscaffolds characterized by specific shapes, sizes and coordination environment. In this regard, inorganic scaffolds can be engineered with photoresponsive units, which need to preserve, amplify or suppress their photochemical properties, depending on the final goal. In the case of multiple photoresponsive components integrated in the same nanoscaffold, the final material can be designed to allow each individual unit either to work in tandem or to communicate with each other (via energy/electron transfer) upon light excitation. Whatever the final goal, once engineered, these NPs possess the great advantage to concentrate a large number of photoactivatable units in a small volume and thus allow producing a “burst” of cytotoxicity in a precisely confined region of space.
This contribution starts with a brief introductory description of the main “unconventional” light-driven therapeutic approaches, which can be useful for the readers not familiar with photochemistry. Afterward, we shall illustrate an overview of the work carried out in our research group over the last years specifically focused on inorganic NPs based on non-metallic- and noble metal scaffolds and highlight the logical design and their potential applications in PDT, NO-PDT and PTT (Fig. 1). In the last part, we also report some examples emphasizing the role of light as convenient reactant in the fabrication of metallic NPs for therapeutic uses, through simple and eco-friendly synthetic procedures.
Section snippets
Unconventional phototherapy: Basic concepts
PDT, NO-PDT and PTT represent major emerging and minimally invasive unconventional therapeutic modalities for cancer, infectious and other malignant diseases. As anticipated above, these approaches exploit appropriate photoprecursors for the generation of 1O2, NO or heat whose cytotoxic effects can be confined to the desired area with great accuracy by directing the incident light. These species share common advantages with respect to conventional drugs such as (i) capability to be multi target
Nonmetallic inorganic NPs
Because of their mesoporous structure and the good biocompatibility, mesoporous silica nanoparticles (MSNPs) are very suitable scaffolds for the integration of functional phototherapeutic components through non-covalent and covalent methodologies. The pores of MSNPs can be fabricated with designed sizes to be accessible to appropriate guest molecules and their inner and outer walls can be readily tailored with a large variety of molecules through well-established synthetic protocols.49 From the
Noble metal-based NPs
Surface chemistry based on thiol terminated units makes the engineering of noble metal NPs quite easy. In the case of photoactivatable compounds, the three-dimensional shape of NPs offers some advantages compared to the bidimensional analogues, such a reduced quenching effects of the excited states of the photoactive units and, in some cases, even enhanced photochemical response due to plasmonic effects.76
Decoration of AuNPs with NO photocages generates nanohybrids of great potential in bimodal
Concluding remarks and future perspectives
In this contribution we have illustrated a panel of inorganic NPs made of different materials, ad-hoc engineered for potential use in “unconventional” therapies. The work described herein demonstrates the central role light plays, not only in the activation of specific therapeutic functionalities with precise spatiotemporal control, but also as a convenient reactant in the fabrication of NPs through simple and eco-friendly synthetic procedures. The examples described show that the creation of
Acknowledgments
S.S. is very grateful to his former students and the collaborators, whose names are listed in the references, for their inestimable contribution in the work described herein. We thank AIRC (Project IG-12834) for financial support.
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