Two-Photon Fluorescence Imaging and Bimodal Phototherapy of Epidermal Cancer Cells with Biocompatible Self-Assembled Polymer Nanoparticles

Abstract

We have developed herein an engineered polymer-based nanoplatform showing the convergence of two-photon fluorescence imaging and bimodal phototherapeutic activity in a single nanostructure. It was achieved through the appropriate choice of three different components: a β-cyclodextrin-based polymer acting as a suitable carrier, a zinc phthalocyanine emitting red fluorescence simultaneously as being a singlet oxygen ((1)O2) photosensitizer, and a tailored nitroaniline derivative, functioning as a nitric oxide (NO) photodonor. The self-assembly of these components results in photoactivable nanoparticles, approximately 35 nm in diameter, coencapsulating a multifunctional cargo, which can be delivered to carcinoma cells. The combination of steady-state and time-resolved spectroscopic and photochemical techniques shows that the two photoresponsive guests do not interfere with each other while being enclosed in their supramolecular container and can thus be operated in parallel under control of light stimuli. Specifically, two-photon fluorescence microscopy allows mapping of the nanoassembly, here applied to epidermal cancer cells. By detecting the red emission from the phthalocyanine fluorophore it was also possible to investigate the tissue distribution after topical delivery onto human skin ex vivo. Irradiation of the nanoassembly with visible light triggers the simultaneous delivery of cytotoxic (1)O2 and NO, resulting in an amplified cell photomortality due to a combinatory effect of the two cytotoxic agents. The potential of dual therapeutic photodynamic action and two-photon fluorescence imaging capability in a single nanostructure make this system an appealing candidate for further studies in biomedical research.

A Three‐Color Fluorescent Supramolecular Nanoassembly of Phototherapeutics Activable by Two‐Photon Excitation with Near‐Infrared Light

“…Our recent resultsh ave shown that the PS 2,w hichi st otally aggregated and photochemically non-responsive in aqueous medium, is effectively encapsulated in al abel-free b-CD branched polymer similar to 1. [13] The encapsulation massively breaks the aggregation of 2,r estoringi ts fluorescence and capabilityt op hotogenerate 1 O 2 in cancerc ells. [13] We have also demonstrated the suitability of this polymericn anocarrier to solubilize the water-insoluble NOPD 3 and to transport it into cancer cells.…”

Clinical Applicability of Whole-Exome Sequencing Exemplified by a Study in Young Adults with the Advanced Cryptogenic Cholestatic Liver Diseases

“…The detailed parameters for running both of these programs are included in Supplementary Material Online File 1 available online at https://doi.org/10.1155/2017/4761962. Additionally, single-nucleotide variant calls were filtered by a variant-filter [12]. If multiple alleles were reported on one position, they were separated by vcfbreakmulti script from vcflib [13].…”

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.…”