A Nanoparticle Platform To Evaluate Bioconjugation and Receptor-Mediated Cell Uptake Using Cross-Linked Polyion Complex Micelles Bearing Antibody Fragments.

Targeted nanomedicines are a promising technology for treatment of disease; however, preparation and characterization of well-defined protein-nanoparticle systems remain challenging. Here, we describe a platform technology to prepare antibody binding fragment (Fab)-bearing nanoparticles and an accompanying real-time cell-based assay to determine their cellular uptake compared to monoclonal antibodies (mAbs) and Fabs. The nanoparticle platform was composed of core-cross-linked polyion complex (PIC) micelles prepared from azide-functionalized PEG-b-poly(amino acids), that is, azido-PEG-b-poly(l-lysine) [N3-PEG-b-PLL] and azido-PEG-b-poly(aspartic acid) [N3-PEG-b-PAsp]. These PIC micelles were 30 nm in size and contained approximately 10 polymers per construct. Fabs were derived from an antibody binding the EphA2 receptor expressed on cancer cells and further engineered to contain a reactive cysteine for site-specific attachment and a cleavable His tag for purification from cell culture expression systems. Azide-functionalized micelles and thiol-containing Fab were linked using a heterobifunctional cross-linker (FPM-PEG4-DBCO) that contained a fluorophenyl-maleimide for stable conjugation to Fabs thiols and a strained alkyne (DBCO) group for coupling to micelle azide groups. Analysis of Fab-PIC micelle conjugates by fluorescence correlation spectroscopy, size exclusion chromatography, and UV-vis absorbance determined that each nanoparticle contained 2-3 Fabs. Evaluation of cellular uptake in receptor positive cancer cells by real-time fluorescence microscopy revealed that targeted Fab-PIC micelles achieved higher cell uptake than mAbs and Fabs, demonstrating the utility of this approach to identify targeted nanoparticle constructs with unique cellular internalization properties.

Polyester micelles for drug delivery and cancer theranostics: Current achievements, progresses and future perspectives.

The development of tumor-targeting nanocarriers is critical important for effective treatment. The synthetic polyesters have demonstrated high potential for developing nanocarriers for cancer theranostics. Especially, the biocompatible and biodegradable polyester micelles have held great promise for cancer therapy and diagnosis, while some candidates have been translated into clinical applications or under clinical trial. In this review, we have provided the state-of-the-art of polyester micelles for drug delivery and cancer theranostics. In addition, we have summarized several major types of polyesters used in the biomedical fields, the current clinical achievements of polyester micelles and recent progresses of multi-functional polyester micelles for tumor molecular imaging and therapeutic applications.

[Enhanced aerobic degradation of low chlorinated biphenyls by constructing surfactants Burkholderia xenovorans LB400 based system].

It has been proposed that the increasing of water solubility of PCBs can enhance the biodegradation efficiency. The biodegradation system of PCBs by Burkholderia xenovorans LB400 in the presence of different surfactants, namely TX-100, Tween 80, RL crude and HPCD were established to investigate the effect of surfactants on the biodegradation of hydrophobic organic compounds. The results indicated that the water solubility ratios of PCB5 and PCB31 were 54.7%-100%, 59.8%-100%; 10.5%-40.8%, 6.8%-31.6%; 10.3%-19.9%, 3.3%-11.6% and 19.5%-34.2%, 4.2%-10.7%, which were accordingly enhanced by TX-100 (CMC = 194 mg · L(-1)), Tween 80 (CMC =13.1 mg · L(-1)), and RL crude (CMC = 50 mg · L(-1)) with concentrations of 1-7 CMC, respectively and HPCD with concentrations of 500-1,500 mg · L(-1). Moreover, the growth inhibition ratio of B. xenovorans LB400 was 30.3%-45.8% with TX-100 concentration of 1-7 CMC, while it was 10.0%-15.4% for Tween 80 with concentration of 0.1-1 CMC; RL crude could boost the growth of strain LB400 as substrate while HPCD exerted no impact on it. The addition of surfactants can improve the biodegradation ratios of PCB31 (5 mg · L(-1)) by 23.7%-65.5% for TX-100, 14.6%-44.3% for Tween 80, 9.6%- 27.2% for RL crude and 15.3%-20.7% for HPCD depending on the surfactant concentrations, while it had minor effects on the biodegradation ratios of PCB5 (10 mg · L(-1)). It is concluded that the promoting effects of surfactant on PCBs biodegradation are mainly due to the increased concentrations of PCBs-surfactant micelles in aqueous solution and when TX-100 and Tween 80 concentrations are set as 1 and 7 CMC, the biodegradation ratios of PCB31 can achieve 100% and 81.7% , while the growth inhibition ratios of B. xenovorans LB400 are 30.3% and 5.4%, respectively.