Supramolecular combination chemotherapy: a pH-responsive co-encapsulation drug delivery system.

Most cancer chemotherapy regimens rely on the use of two or more chemotherapeutic agents. However, achieving the best possible dosing of the individual drugs can be challenging due to differences in metabolism, uptake, and clearance among other factors. Here we describe a supramolecular strategy for achieving drug delivery in which the loading ratio of two active components is easily defined. Specifically, we report the formation of aggregates comprised of self-assembled amphiphiles between carboxylatopillar[6]arene (CP6A) and an oxaliplatin (OX)-type Pt(iv) prodrug (PtC10). The association constant (K a) for the underlying host-guest interaction at pH 7.4 ((1.16 ± 0.03) × 104 M-1) is an order of magnitude higher than at pH 5.0 ((1.73 ± 0.15) × 103 M-1). A second chemotherapeutic, doxorubicin (DOX), may be encapsulated in the resulting vesicles (PtC10⊂CP6A) to give a supramolecular combination chemotherapeutic system DOX@PtC10⊂CP6A. Drug release studies served to confirm that PtC10 and DOX are released in acidic environments. Support for a synergistic antiproliferative effect relative to PtC10 + DOX came from cellular studies of DOX@PtC10⊂CP6A using the human liver hepatocellular carcinoma (HepG-2) cell line. In vivo studies revealed that DOX@PtC10⊂CP6A is not only able to retard tumor growth efficiently but also reduce drug-related toxic side effects in BALB/c nude mice bearing HepG-2 subcutaneous tumor xenografts. These favorable findings are attributed to the formation of a ternary complex that benefits from an enhanced permeability and retention (EPR) effect in vivo while allowing for the pH-based release of PtC10 and DOX at the tumor site.

Oligo(para-phenylenes)s-Oligoarginine Conjugates as Effective Antibacterial Agents with High Plasma Stability and Low Hemolysis.

Bacterial infections have become a global threat to human health, and the design of antibacterial agents is always an urgent task for biomedicine. Amphiphilic antibacterial agents with a different mechanism of action from traditional antibiotics have attracted researchers' attention more and more in recent years. In this work, a series of antibacterial conjugates composed of oligo(para-phenylenes)s and oligoarginine were synthesized, and their antibacterial activity was investigated. 2,2'-Biphenyl, 2,2″-terphenyl, and 2,2‴-quaterphenyl were conjugated with one or two triarginines by "click" chemical reactions to form compounds. The conjugates showed antibacterial activity against the typical Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria, relatively low cytotoxicity to L929 cell line, and hemolytic activity in a certain range of concentration. Among these conjugates, 2,2‴-quaterphenyl-triarginine conjugate (2,2‴-QP-1) showed the highest antibacterial activity against both E. coli and S. aureus. Besides, it presented better stability in plasma compared with the positive control peixiganan. The antimicrobial mechanism of 2,2‴-QP-1 was also investigated by transmission electron microscopy and confocal laser scanning microscopy, showing that 2,2‴-QP-1 could interact with the bacterial membrane and then disrupt the membrane structure. This work demonstrated a prospective approach for the design of antibacterial agents with highly effective antibacterial activity, high stability in plasma, and low cytotoxicity.

Chiral determination of cinchonine using an electrochemiluminescent sensor with molecularly imprinted membrane on the surfaces of magnetic particles.

A novel molecular imprinting electrochemiluminescence sensor for detecting chiral cinchonine molecules was developed with a molecularly imprinted polymer membrane on the surfaces of magnetic microspheres. Fe3 O4 @Au nanoparticles modified with 6-mercapto-beta-cyclodextrin were used as a carrier, cinchonine as a template molecule, methacrylic acid as a functional monomer and N,N'-methylenebisacrylamide as a cross-linking agent. Cinchonine was specifically recognized by the 6-mercapto-beta-cyclodextrin functional molecularly imprinted polymer and detected based on enhancement of the electrochemiluminescence intensity caused by the reaction of tertiary amino structures of cinchonine molecules with Ru(bpy)32+ . Cinchonine concentrations of 1 × 10-10 to 4 × 10-7  mol/L showed a good linear relationship with changes of the electrochemiluminescence intensity, and the detection limit of the sensor was 3.13 × 10-11  mol/L. The sensor has high sensitivity and selectivity, and is easy to renew. It was designed for detecting serum samples, with recovery rates of 98.2% to 107.6%.