Bradykinin-Potentiating Peptide-Paclitaxel Conjugate Directed at Ectopically Expressed Angiotensin-Converting Enzyme in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer with poor prognosis. Here, we present a peptide-drug conjugate (PDC)─bradykinin-potentiating peptide-paclitaxel (BPP-PTX) conjugate─synthesized by conjugating BPP9a with PTX via a succinyl linker. BPP-PTX targets the angiotensin-converting enzyme (ACE) on TNBC cells. ACE was found to be ectopically expressed in two TNBC cell lines but was absent in both the receptor-positive breast cancer cell line and healthy kidney cell line. Overexpression, knockdown, and competitive inhibition experiments demonstrated ACE-mediated cytotoxicity of BPP-PTX. In vivo, ACE-positive tumors were enriched with BPP-PTX, with the PDC being better tolerated than plain PTX. Compared with plain PTX, BPP-PTX exhibited improved tumor-suppressive effects in MDA-MB-468 xenografted female nude mice. Meanwhile, BPP-PTX resulted in less body weight loss and white blood cell reduction toxicity. These results collectively imply the novelty, efficacy, and low-toxicity profile of BPP-PTX as a potential therapeutic for ACE-positive TNBC.

[Investigation on effect of PVP on morphological changes and crystallization behavior of nylon 6 in PVP/nylon 6 blends by FTIR spectroscopy].

Temperature-dependent FT IR, DSC and POM were used to investigate the interaction between PVPK90 and nylon 6 molecules and its effect on the thermal behavior and morphology of nylon 6. DSC results suggest that the melting and crystallization behavior of nylon 6 are obviously influenced by the introduction of PVP. With the PVP content increasing, the crystallization temperature, melting temperature and the crystallinity of nylon 6 decreased, and eventually, both the exothermal and endothermic peaks could not be observed when the PVP content reached 80%, implying that the aggregation structure of nylon 6 changes from the crystalline state to the amorphous state. FTIR provided the evidence of the interaction between PVP and nylon 6 molecules. With the increase in PVP content, the peak position of nu N-H of nylon 6 gradually shifts from 3311 to 3300 cm(-1) with 90% content of PVP, and the half height peak width is broadened correspondingly. Three peaks were obtained in the carbonyl group absorption band for PVPK90/Nylon 6(50/50) and PVPK90/Nylon 6(80/20) blends from the curve-fitting results. With the addition of PVP molecules, the nu C=O of nylon 6 shifts to higher wave number and a new peak located at about 1620 cm(-1) appears and its peak area increases with the content of PVP. The above spectral variation of nu C=O and nu N-H in the PVPK90/Nylon 6 blend indicates that the carbonyl group of PVP could form H-bonding with N-H group of nylon 6 molecule, and partially destroy the hydrogen bonding between the nylon 6 molecules. POM results showed that the spherulitic size of nylon 6 decreases with the increment of the PVP and becomes more imperfect, and when the PVP content reaches 80%, no spherulites could be observed. This phenomenon is attributed to the molecular interactions between the PVP and the nylon 6 molecules, which weakens the free mobility of nylon 6 chains to form regular packing and eventually induces the change in the spherulitic morphology of nylon 6. In summary, the molecular interactions between the carbonyl group of PVP molecules and N-H group of nylon 6 molecules account for the above changes in the crystalline structure and the morphology of nylon 6 in the blends.

[Investigation on composites of europium fluorescent complexes and polyvinylpyrrolidone].

In order to investigate the relationship between the aggregation structure and fluorescence properties of composites of rare earth fluorescent complexes and polymers, the fluorescent complexes of Eu(TTA)3 x 2H2O and Eu(TTA)3 x (TPPO)2 were synthesized by the reaction of TTA (2-thenoyltrifluoroacetone), TPPO (triphenylphosphine oxide) and EuCl3, and their composites with polyvinylpyrrolidone (PVP K30) were prepared. The fluorescence spectroscopy, FTIR spectroscopy and TEM were used to characterize these composites. Fluorescence spectroscopy results indicated that the fluorescence intensity of the PVP/Eu(TTA)3 x 2H2O composites is obviously improved compared with that of the Eu(TTA)3 x 2H2O complexes. For the composites with the molar ratio of the complexes to the repeat unit of PVP being 1:35, the intensity of 612 nm emission peak of the composites is 5.5 times for PVP/Eu(TTA)3 x 2H2O and 0.3 times for PVP/Eu(TTA)3 x (TPPO)2 higher than that of the corresponding pure rare earth fluorescent complexes. And the emission intensity ratio of 612 to 590 nm peak is 14.7 in PVP/Eu (TTA)3 x 2H2O composite, larger than that of Eu(TTA)3 x 2H2O complexes. These results suggested that the luminescent properties of the europium fluorescent complexes were obviously enhanced in the presence of PVP matrix and there are interactions between the fluorescence complexes and PVP molecules. In the presence of PVPK30, the FTIR spectra of the Eu(TTA)3 x 2H2O complexes were obviously influenced as well. Based on the curve-fitting results of IR spectra of PVP/Eu(TTA)3 2H2O composites with the molar ratio of repeat unit of PVP to Eu(TTA)3 x 2H2O being 7:1 and 2:1, multiple absorption peaks of nu C=O are observed. The IR spectral variations indicated that there are coordination interactions between Eu3+ ions and the carbonyl groups of PVP, and multiple coordination fashion exists. TEM results showed that there are microphase separation structures in PVP/Eu(TTA)3 x 2H2O and PVP/Eu(TTA)3 x (TPPO)2 composites. The microphase separation phenomenon in composite of PVP/Eu(TTA)3 x (TPPO)2 is more obvious than that of the PVP/Eu(TTA)3 x 2H2O. And the Europium complexes are in amorphous state, which further proved the interactions between PVP molecules and the rare earth fluorescence complexes Eu(TTA)3 x 2H2O and Eu(TTA)3 x (TPPO)2.