Third-Generation Anticancer Photodynamic Therapy Systems Based on Star-like Anionic Polyacrylamide Polymer, Gold Nanoparticles, and Temoporfin Photosensitizer.

Photodynamic therapy (PDT) is a non-invasive anticancer treatment that uses special photosensitizer molecules (PS) to generate singlet oxygen and other reactive oxygen species (ROS) in a tissue under excitation with red or infrared light. Though the method has been known for decades, it has become more popular recently with the development of new efficient organic dyes and LED light sources. Here we introduce a ternary nanocomposite: water-soluble star-like polymer/gold nanoparticles (AuNP)/temoporfin PS, which can be considered as a third-generation PDT system. AuNPs were synthesized in situ inside the polymer molecules, and the latter were then loaded with PS molecules in an aqueous solution. The applied method of synthesis allows precise control of the size and architecture of polymer nanoparticles as well as the concentration of the components. Dynamic light scattering confirmed the formation of isolated particles (120 nm diameter) with AuNPs and PS molecules incorporated inside the polymer shell. Absorption and photoluminescence spectroscopies revealed optimal concentrations of the components that can simultaneously reduce the side effects of dark toxicity and enhance singlet oxygen generation to increase cancer cell mortality. Here, we report on the optical properties of the system and detailed mechanisms of the observed enhancement of the phototherapeutic effect. Combinations of organic dyes with gold nanoparticles allow significant enhancement of the effect of ROS generation due to surface plasmonic resonance in the latter, while the application of a biocompatible star-like polymer vehicle with a dextran core and anionic polyacrylamide arms allows better local integration of the components and targeted delivery of the PS molecules to cancer cells. In this study, we demonstrate, as proof of concept, a successful application of the developed PDT system for in vitro treatment of triple-negative breast cancer cells under irradiation with a low-power LED lamp (660 nm). We consider the developed nanocomposite to be a promising PDT system for application to other types of cancer.

Anti-cancer activity of zinc-tetraphenylporphyrin photosensitizer/dextran-graft-polyacrylamide copolymer/Au(Ag) nanoparticle nanohybrids.

A comparative study of in vitro anti-cancer photodynamic activities of three-component zinc-tetraphenylporphyrin photosensitizer/dextran-graft-polyacrylamide copolymer/Au(Ag) nanoparticle (ZnTPP/D-g-PAA/Au(Ag)NP) nanohybrids on LNCaP prostate cancer cells was carried out under 420 nm light irradiation with low power. A significant cytotoxic effect was revealed for both ZnTPP/D-g-PAA/AgNP and ZnTPP/D-g-PAA/AuNP nanohybrids, where ZnTPP/D-g-PAA/AgNP nanohybrids exhibited considerably higher anticancer activity (82%) compared to ZnTPP/D-g-PAA/AuNP nanohybrids (45%). The higher activity of silver-containing nanohybrids is rationalized based on two factors. The first factor is the resonance of 420 nm light with a absorption Soret peak of the ZnTPP photosensitizer and a localized surface plasmon mode in Ag nanoparticles. Correspondingly, the plasmon enhancement of reactive oxygen species photogeneration by ZnTPP molecules was considerably higher for the nanohybrid containing silver compared to the one containing gold. The second factor is the higher cytotoxicity of Ag nanoparticles compared to Au ones. The study results prove the high potential of D-g-PAA/Ag(Au)NP nanohybrids combined with 420 nm light irradiation with low power in the photodynamic treatment of prostate cancer.

Combined Dextran-Graft-Polyacrylamide/Zinc Oxide Nanocarrier for Effective Anticancer Therapy in vitro.

Introduction: Cancer chemotherapy faces two major challenges - high toxicity of active substances and tumor resistance to drugs. Low toxic nanocarriers in combination with anticancer agents can significantly increase the effectiveness of therapy. Modern advances in nanotechnology make it easy to create materials with the necessary physical and chemical properties. Methods: Two hybrid nanosystems of dextran-polyacrylamide/ zinc oxide nanoparticles (D-PAA/ZnO NPs) were synthesized in aqueous solution with zinc sulphate (D-PAA/ZnO NPs (SO42-)) and zinc acetate (D-PAA/ZnO NPs (-OAc)). The light absorption, fluorescence, dynamic light scattering and transmission electron microscopy for nanocomposite characterization were used. MTT, neutral red uptake and scratch assays were selected as fibroblasts cytotoxicity assays. Cytotoxicity was tested in vitro for normal fibroblasts, MAEC, prostate (LNCaP, PC-3, DU-145) and breast (MDA-MB-231, MCF-7) cancer cells lines. Immunocytochemical methods were used for detection of Ki-67, p53, Bcl-2, Bax, e-cadherin, N-cadherin and CD44 expression. Acridine orange was used to detect morphological changes in cells. Results: The radius of ZnO NPs (SO42-) was 1.5 nm and ZnO NPs (-OAc) was 2 nm. The nanosystems were low-toxic to fibroblasts, MAEC. Cells in the last stages of apoptosis with the formation of apoptotic bodies were detected for all investigated cancer cell lines. Proapoptotic proteins expression in cancer cells indicates an apoptotic death. Increased expression of E-cadherin and N-cadherin was registered for cancer cells line LNCaP, PC-3, DU-145 and MCF-7 after 48 h incubation with D-PAA/ZnO NPs (SO42-). Conclusion: The nanosystems were low-toxic to fibroblasts, MAEC. The D-PAA/ZnO NPs nanosystem synthesized using zinc sulphate demonstrates high cytotoxicity due to destruction of various types of cancer cells in vitro and potentially increases adhesion between cells. Thus, our findings indicate the selective cytotoxicity of D-PAA/ZnO NPs against cancer cells and can be potentially used for cancer treatment.

Thermoresponsive Zinc TetraPhenylPorphyrin Photosensitizer/Dextran Graft Poly(N-IsoPropylAcrylAmide) Copolymer/Au Nanoparticles Hybrid Nanosystem: Potential for Photodynamic Therapy Applications.

The thermoresponsive Zinc TetraPhenylPorphyrin photosensitizer/Dextran poly (N-isopropylacrylamide) graft copolymer/Au Nanoparticles (ZnTPP/D-g-PNIPAM/AuNPs) triple hybrid nanosystem was synthesized in aqueous solution as a nanodrug for potential use in thermally driven and controlled photodynamic therapy applications. The aqueous solution of the nanosystem has demonstrated excellent stability in terms of aggregation and sedimentation several days after preparation. Optimal concentrations of the components of hybrid nanosystem providing the lowest level of aggregation and the highest plasmonic enhancement of electronic processes in the photosensitizer molecules have been determined. It has been revealed that the shrinking of D-g-PNIPAM macromolecule during a thermally induced phase transition leads to the release of both ZnTPP molecules and Au NPs from the ZnTPP/D-g-PNIPAM/AuNPs macromolecule and the strengthening of plasmonic enhancement of the electronic processes in ZnTPP molecules bound with the polymer macromolecule. The 2.7-fold enhancement of singlet oxygen photogeneration under resonant with surface plasmon resonance has been observed for ZnTPP/D-g-PNIPAM/AuNPs proving the plasmon nature of such effect. The data obtained in vitro on wild strains of Staphylococcus aureus have proved the high potential of such nanosystem for rapid photodynamic inactivation of microorganisms particular in wounds or ulcers on the body surface.

Plasmonic enhancement of the antibacterial photodynamic efficiency of a zinc tetraphenylporphyrin photosensitizer/dextran graft polyacrylamide anionic copolymer/Au nanoparticles hybrid nanosystem.

A zinc tetraphenylporphyrin photosensitizer/dextran graft polyacrylamide anionic copolymer/Au nanoparticles (ZnTPP/D-g-PAAan/AuNPs) triple hybrid nanosystem was synthesized in water-based solution as a nanodrug for potential photodynamic therapy applications. Dynamic light scattering studies showed that the nanosystem is stable against aggregation and sedimentation for several days after preparation. The dependence of the ZnTPP fluorescence intensity on the gold concentration in the ZnTPP/D-g-PAAan/AuNPs nanosystem has been revealed to be non-monotonic, with a maximum 2.5-fold enhancement at a concentration of 0.008 g L-1. The non-monotonic dependence was explained to be caused by two competing processes, namely plasmonic enhancement and FRET, indicating the existence of an optimal concentration of Au NPs that can provide the highest plasmonic enhancement of the electronic processes involving the ZnTPP photosensitizer. A 2.6-fold enhancement of singlet oxygen photogeneration under excitation resonant with the localized surface plasmon resonance of the Au NPs has been detected for ZnTPP/D-g-PAAan/AuNPs, proving the plasmonic origin of this phenomenon. The high bactericidal efficiency of ZnTPP/D-g-PAAan/AuNPs water-based solution under 420 nm and 530 nm light irradiation was revealed against wild strains of Staphylococcus aureus. Therefore, the ZnTPP/D-g-PAAan/AuNPs nanosystem can potentially be used in photodynamic therapy for the prevention and treatment of the bacterial contamination of open wounds.