Conjugation with L,L-diphenylalanine Self-Assemblies Enhances In Vitro Antitumor Activity of Phthalocyanine Photosensitizer.

We present the synthesis and characterization of new peptide conjugates obtained by hierarchical co-assembly of L,L-diphenylalanine (FF) and zinc phthalocyanine complexes (ZnPc) in water. Self-assembly capabilities under defined conditions were investigated by scanning electron microscopy, and photophysical properties were evaluated using UV-Vis and fluorescence spectroscopy. AFM observations demonstrated that these ZnPcs form different highly ordered arrays on the crystalline faces of the FF microplates and that surface roughness significantly changes with the presence of differently substituted phthalocyanine units. XRD assays showed that the overall molecular packing of the conjugates is organized according to a hexagonal symmetry, with ZnPcs hosted in the interstices of the peptide phase. In vitro photodynamic studies were conducted on human breast cancer MCF-7 cells to investigate both cellular uptake and cytotoxicity. It was shown that FF self-assemblies are not toxicity and enhance accumulation of ZnPc in MCF-7 cells, improving apoptotic cell death upon irradiation. Our findings demonstrate enhancement of ZnPc antitumor efficiency by FF conjugates and a proof-of-concept for new photosensitizer carriers based on peptide conjugates.

Photochemical and Photophysical Properties of Phthalocyanines Modified with Optically Active Alcohols.

Three phthalocyanine derivatives were synthesized and characterized: one modified with a racemic mixture of 1-(4-bromophenyl)ethanol and two other macrocycles modified with each one of the enantioenriched isomers (R)-1-(4-bromophenyl)ethanol and (S)-1-(4-bromophenyl)ethanol. The compounds were characterized by 1H-NMR spectroscopy, mass spectrometry, UV-Vis absorption, and excitation and emission spectra. Additionally, partition coefficient values and the quantum yield of the generation of oxygen reactive species were determined. Interestingly, the phthalocyanine containing a (R)-1-(4-bromophenyl)ethoxy moiety showed higher quantum yield of reactive oxygen species generation than other compounds under the same conditions. In addition, the obtained fluorescence microscopy and cell viability results have shown that these phthalocyanines have different interactions with mammary MCF-7 cells. Therefore, our results indicate that the photochemical and biological properties of phthalocyanines with chiral ligands should be evaluated separately for each enantiomeric species.

Preoperative pulmonary rehabilitation versus chest physical therapy in patients undergoing lung cancer resection: a pilot randomized controlled trial.

OBJECTIVE: To evaluate the effect of 4 weeks of pulmonary rehabilitation (PR) versus chest physical therapy (CPT) on the preoperative functional capacity and postoperative respiratory morbidity of patients undergoing lung cancer resection. DESIGN: Randomized single-blinded study. SETTING: A teaching hospital. PARTICIPANTS: Patients undergoing lung cancer resection (N=24). INTERVENTIONS: Patients were randomly assigned to receive PR (strength and endurance training) versus CPT (breathing exercises for lung expansion). Both groups received educational classes. MAIN OUTCOME MEASURES: Functional parameters assessed before and after 4 weeks of PR or CPT (phase 1), and pulmonary complications assessed after lung cancer resection (phase 2). RESULTS: Twelve patients were randomly assigned to the PR arm and 12 to the CPT arm. Three patients in the CPT arm were not submitted to lung resection because of inoperable cancer. During phase 1 evaluation, most functional parameters in the PR group improved from baseline to 1 month: forced vital capacity (FVC) (1.47L [1.27-2.33L] vs 1.71L [1.65-2.80L], respectively; P=.02); percentage of predicted FVC (FVC%; 62.5% [49%-71%] vs 76% [65%-79.7%], respectively; P<.05); 6-minute walk test (425.5±85.3m vs 475±86.5m, respectively; P<.05); maximal inspiratory pressure (90±45.9cmH(2)O vs 117.5±36.5cmH(2)O, respectively; P<.05); and maximal expiratory pressure (79.7±17.1cmH(2)O vs 92.9±21.4cmH(2)O, respectively; P<.05). During phase 2 evaluation, the PR group had a lower incidence of postoperative respiratory morbidity (P=.01), a shorter length of postoperative stay (12.2±3.6d vs 7.8±4.8d, respectively; P=.04), and required a chest tube for fewer days (7.4±2.6d vs 4.5±2.9d, respectively; P=.03) compared with the CPT arm. CONCLUSIONS: These findings suggest that 4 weeks of PR before lung cancer resection improves preoperative functional capacity and decreases the postoperative respiratory morbidity.