No abstract

pH-responsive biodegradable micelles were prepared from block copolymers comprising of a novel acid-labile polycarbonate hydrophobe and poly(ethylene glycol) (PEG). Two new cyclic aliphatic carbonate monomers, mono-2,4,6-trimethoxybenzylidene-pentaerythritol carbonate (TMBPEC, 2a) and mono-4-methoxybenzylidene-pentaerythritol carbonate (MBPEC, 2b) were designed and successfully synthesized via a two-step procedure. The ring-opening polymerization of 2a or 2b in the presence of methoxy PEG in dichloromethane at 50 °C using zinc bis[bis(trimethylsilyl)amide] as a catalyst yielded the corresponding block copolymers PEG-PTMBPEC (3a) or PEG-PMBPEC (3b) with low polydispersities (PDI 1.03-1.04). The copolymerization of D,L-lactide (DLLA) and 2a under otherwise the same conditions could also proceed smoothly to afford PEG-P(TMBPEC-co-DLLA) (3c) block copolymer. These block copolymers readily formed micelles in water with sizes of about 120 nm as determined by dynamic light scattering (DLS). The hydrolysis of the acetals of the polycarbonate was investigated using UV/vis spectroscopy. The results showed that the acetals of micelles 3a, while stable at pH 7.4 are prone to rapid hydrolysis at mildly acidic pH of 4.0 and 5.0, with a half-life of 1 and 6.5 h, respectively. The acetal hydrolysis resulted in significant swelling of micelles, as a result of change of hydrophobic polycarbonate to hydrophilic polycarbonate. In comparison, the acetals of PMBPEC of micelles 3b displayed obviously slower hydrolysis at the same pH. Both paclitaxel and doxorubicin could be efficiently encapsulated into micelles 3a achieving high drug loading content (13.0 and 11.7 wt %, respectively). The in vitro release studies showed clearly a pH dependent release behavior, that is, significantly faster drug release at mildly acidic pH of 4.0 and 5.0 compared to physiological pH. These pH-responsive biodegradable micelles are promising as smart nanovehicles for targeted delivery of anticancer drugs.

The abnormal expression of tumor-related proteases plays a critical role in cancer invasion, progression, and metastasis. Therefore, it is considerably meaningful to non-invasively assess the proteases' activity in vivo for both tumor diagnosis and therapeutic evaluation. Herein, we report an activatable probe constructed with a near-infrared dye (Cy5.5) and a quencher (QSY21) covalently linked through a peptide substrate of matrix metalloproteinases-2 (MMP-2) that was chosen as a model for tumor-associated proteases. Upon cleavage with activated MMP-2, this probe emitted an MMP-2-concentration-dependent fluorescence. Quite unexpectedly, owing to the variation in the aggregation state of both the dye and its quencher as a consequence of the cleavage, the responsive probe presented a dramatic MMP-2-concentrationdependent absorption at around 680 nm, while that at around 730 nm was MMP-2 concentration independent. These features allowed detection of MMP-2 activity via both fluorescence and photoacoustic (PA) imaging in vitro, respectively. Moreover, taking the PA signal at 730 nm as an internal reference, the PA signal at 680 nm allowed quantitative detection of MMP-2 expression in breast cancer in vivo. We thus envision that our current approach would offer a useful tool for studying the malignant impacts of versatile tumor-associated proteases in vivo.

By introducing a coplanar fluorenone into the center of an azo molecule, the turn-on voltages of the ternary memory devices are significantly decreased to lower than -2 V due to the improved crystallinity and the reduced charge injection barrier. The resulting low-power consumption devices will have great potential applications in high-performance chips for future portable nanoelectronic devices.

An efficient synthesis of polyhydroquinoline derivatives were reported via four-component coupling reactions of aldehydes, dimedone, ethyl acetoacetate and ammonium acetate in the presence of a catalytic amount of ionic liquid under solvent free conditions. In the meantime, the catalytic effect of different ionic liquids on the reaction has also been investigated.