A Cyclodextrin‐Based Nanoassembly with Bimodal Photodynamic Action

Abstract

We have developed a supramolecular nanoassembly capable of inducing remarkable levels of cancer cell mortality through a bimodal action based on the simultaneous photogeneration of nitric oxide (NO) and singlet oxygen ((1)O(2)). This was achieved through the appropriate incorporation of an anionic porphyrin (as (1)O(2) photosensitizer) and of a tailored NO photodonor in different compartments of biocompatible nanoparticles based on cationic amphiphilic cyclodextrins. The combination of steady-state and time-resolved spectroscopic techniques showed the absence of significant intra- and interchromophoric interaction between the two photoactive centers embedded in the nanoparticles, with consequent preservation of their photodynamic properties. Photodelivery of NO and (1)O(2) from the nanoassembly on visible light excitation was unambiguously demonstrated by direct and real-time monitoring of these transient species through amperometric and time-resolved infrared luminescence measurements, respectively. The typical red fluorescence of the porphyrin units was essentially unaffected in the bichromophoric nanoassembly, allowing its localization in living cells. The convergence of the dual therapeutic action and the imaging capacities in one single structure makes this supramolecular architecture an appealing, multifunctional candidate for applications in biomedical research.

Cyclodextrin-based supramolecular systems for drug delivery: Recent progress and future perspective

“…In vitro studies based on HeLa cells evidenced the photodynamic efficacy of TPPS-loaded nanomedicines, resulting in significant cell death upon illumination with visible light. Furthermore, biomodal photodynamic nanomedicines simultaneously photogenerating nitric oxide (NO) and singlet oxygen ( 1 O 2 ), can be fabricated by encapsulating both TPPS and a NO photodonor into the nanoassemblies wherein hydrophobic, electrostatic, and inclusion interactions may be involved [116]. Photodelivery of NO and 1 O 2 from the nanoassembly upon visible light excitation was evidenced by detecting these transient species.…”

Photodynamic Therapy for Cancer: Principles, Clinical Applications, and Nanotechnological Approaches

“…Finally, since NO release is independent on O 2 availability, it can potentially very well complement PDT at the onset of hypoxic conditions. Interesting results in this fi eld have been obtained by employing light-activated nanoassemblies delivering nitric oxide, PS, and conventional anticancer drugs (Fraix et al 2013a , b ;Kandoth et al 2012 ;Sortino 2010 ;Swaminathan et al 2014 ).…”

Nitric Oxide Releasing Nanomaterials for Cancer Treatment: Current Status and Perspectives

“…In the literature, several papers describe the synthesis, characterization, and biomedical applications of different NO-releasing nanomaterials, including metallic nanoparticles, liposomes, dendrimers, silica nanoparticles, polymeric particles, carbon nanotubes, and quantum dots [17,31,[34][35][36]38,40,[42][43][44][45][46][47][48][49]. However, the use of NO-releasing nanomaterials in cancer treatment is a relatively new approach that needs to be explored further.…”