Tat/HA2 Peptides Conjugated AuNR@pNIPAAm as a Photosensitizer Carrier for Near Infrared Triggered Photodynamic Therapy.

To achieve an efficiency of intracellular photosensitizers (PSs) delivery and efficacy of photodynamic therapy, we have developed a novel class of PS formulation for encapsulating sulfonated aluminum phthalocyanine (AlPcS4) by taking advantage of the membrane-disruptive peptides Tat/HA2 and the photothermally triggered delivery system using AuNR@pNIPAAm. The coordinated effects of cell penetrating peptide Tat and fusogenic peptide HA2 could enhance the efficient cellular internalization and endo/lysosome escape of PSs delivery systems. Singlet oxygen generation was inhibited due to the reaction between loaded AlPcS4 and Au nanorods, which indicated that the AlPcS4-loaded, AuNR@pNIPAAm delivery system might be nonphototoxic in the circulatory system. However, this PSs-loaded nanosystem became highly phototoxic as it underwent the near-infrared irradiation by using the combined lights of 808 and 680 nm. Upon irradiation, the Tat/HA2 conjugated AuNR@pNIPAAm-Pc elicited an active photodynamic response against the cancer cells, leading to effective cells killing via mitochondria-associated apoptotic pathway. This study also demonstrated improved PDT therapeutic efficacy after intravenous administration of Tat/HA2-AuNR@pNIPAAm-Pc and the subsequent lights irradiations in tumor-bearing mice. We describe here a strategy for enhanced photodynamic eradication of solid tumors by endo/lysosomal escape and highlight the great promise of peptide-based nanocarriers used for cancer therapy.

Shape dependence of gold nanoparticles on in vivo acute toxicological effects and biodistribution.

The toxicity and biodistribution in vivo of various morphologies of Au nanoparticles (AuNPs) were studied by using KM mice. The quantitative analysis of Au in each tissue of mice was done by using the Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Sphere-shaped AuNPs displayed the best biocompatibility, compared with rod- and cube-shaped of AuNPs, and rod-shaped AuNPs was more toxic than cube-shaped AuNPs. In vivo biodistribution study revealed all AuNPs were preferentially accumulated in organ of liver and spleen. The findings from this study thus revealed that the toxicity and biodistribution in vivo of AuNPs are shape dependent.

Ferulic acid delayed amyloid ß-induced pathological symptoms by autophagy pathway via a fasting-like effect in Caenorhabditis elegans.

The amyloid ß (Aß) generation or aggregation plays a crucial role in Alzheimer's disease (AD). Autophagy agonists, which function as the clearance of Aß, could be the potential drug candidates against AD. In staple food crops, ferulic acid (FA) is an enormously copious and almost ubiquitous phenolic antioxidant. In the present study, FA significantly inhibited Aß-induced pathological symptoms of paralysis and hypersensitivity to exogenous serotonin, meanwhile restrained Aß monomers, oligomers, and deposits in AD C. elegans. FA increased the expression of autophagy reporter LGG-1 and enhanced autophagy flux. However, the autophagy inhibitors abolished the restrictive action of FA on the worm paralysis phenotype. According to these results, FA triggered autophagy and ameliorated Aß-induced pathological symptoms by the autophagy pathway. Moreover, FA activated the HLH-30 transcription factor to nuclear localization, which acts upstream of autophagy in fasted animals, reduced the level of lipids, but affected nor the growth of E. coli OP50, neither animal food intake behavior. These suggest that FA induced a fasting-like effect to activate the autophagy pathway. Additionally, FA ameliorated poly Q aggregations in Huntington's disease worm. Thus, FA could not only affect AD, broadly but also neurodegenerative diseases characterized by misfolded or aggregated proteins.

Synthesis and characterization of NIR-responsive Aurod@pNIPAAm-PEGMA nanogels as vehicles for delivery of photodynamic therapy agents.

A near-infrared (NIR)-responsive Aurod@pNIPAAm-PEGMA nanogel was synthesized in two steps, growing a PEGMA monolayer on the surface of gold nanorods (AuNRs), followed by in situ polymerization and cross-linking of N-iso-propylacrylamide (NIPAAm) and poly-(ethylene glycol)-methacrylate (PEGMA). The AuNRs and Aurod@pNIPAAm-PEGMA nanogel were characterized by UV-vis spectroscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, and transmission electron microscopy, respectively. The lower critical solution temperature of the Aurod@pNIPAAm-PEGMA nanogel could be tuned by changing the molar ratio of NIPAAm/PEGMA. The NIR-mediated drug release behavior of the Aurod@pNIPAAm-PEGMA nanogel was studied with zinc phthalocyanines (ZnPc4) as a drug model. It was also demonstrated that the loaded ZnPc4 could keep the capability of generating singlet oxygen, and the in vitro study showed a great photodynamic therapy (PDT) effect on Hela cells. It thus indicated the potential of this Aurod@pNIPAAm-PEGMA nanogel for application as a drug carrier in PDT, which might make contributions to oncotherapy.