zn(ii)-phthalocyanine and Carcinoma--Squamous-Cell

Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Indoles; Isoindoles; Liposomes; Mouth Neoplasms; Organometallic Compounds; Pharyngeal Neoplasms; Photochemotherapy; Photosensitizing Agents; Squamous Cell Carcinoma of Head and Neck; Zinc Compounds

Background Material and Methods Results Conclusions.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Carcinoma, Squamous Cell; Cell Line, Tumor; Female; Head and Neck Neoplasms; HeLa Cells; Humans; Indoles; Isoindoles; Liposomes; Mouth Neoplasms; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Squamous Cell Carcinoma of Head and Neck; Uterine Cervical Neoplasms; Zinc Compounds

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.

Topics: Antineoplastic Agents; beta-Cyclodextrins; Biocompatible Materials; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drug Carriers; Drug Screening Assays, Antitumor; Epichlorohydrin; Humans; Indoles; Isoindoles; Microscopy, Fluorescence; Molecular Structure; Nanoparticles; Nitric Oxide; Organometallic Compounds; Photons; Photosensitizing Agents; Polymers; Singlet Oxygen; Skin Neoplasms; Zinc Compounds