Endogenous pH-responsive nanoparticles with programmable size changes for targeted tumor therapy and imaging applications.

Nanotechnology-based antitumor drug delivery systems, known as nanocarriers, have demonstrated their efficacy in recent years. Typically, the size of the nanocarriers is around 100 nm. It is imperative to achieve an optimum size of these nanocarriers which must be designed uniquely for each type of delivery process. For pH-responsive nanocarriers with programmable size, changes in pH (~6.5 for tumor tissue, ~5.5 for endosomes, and ~5.0 for lysosomes) may serve as an endogenous stimulus improving the safety and therapeutic efficacy of antitumor drugs. This review focuses on current advanced pH-responsive nanocarriers with programmable size changes for anticancer drug delivery. In particular, pH-responsive mechanisms for nanocarrier retention at tumor sites, size reduction for penetrating into tumor parenchyma, escaping from endo/lysosomes, and swelling or disassembly for drug release will be highlighted. Additional trends and challenges of employing these nanocarriers in future clinical applications are also addressed.

Engineering Porous Poly(lactic acid) Scaffolds with High Mechanical Performance via a Solid State Extrusion/Porogen Leaching Approach.

A knotty issue concerning the poor mechanical properties exists in the porogen leaching approach to porous scaffolds, despite its advantage in tuning pore structure. To address this hurdle, solid state extrusion (SSE) combined with porogen leaching was utilized to engineer porous scaffolds of poly(lactic acid) (PLA). Advances introduced by poly(ethylene glycol) (PEG) caused the PLA ductile to be processed and, on the other hand, enabled the formation of interconnected pores. Thus, a well-interconnected porous architecture with high connectivity exceeding 97% and elevated porosity over 60% was obtained in the as-prepared PLA scaffolds with the composition of NaCl higher than 75.00 wt % and PEG beyond 1.25 wt %. More strikingly, the pore walls of macropores encompassed countless micropores and rough surface topography, in favor of transporting nutrients and metabolites as well as cell attachment. The prominent compressive modulus of the PLA scaffolds was in the range of 85.7⁻207.4 MPa, matching the normal modulus of human trabecular bone (50⁻250 MPa). By means of alkaline modification to improve hydrophilicity, biocompatible porous PLA scaffolds exhibited good cell attachment. These results suggest that the SSE/porogen leaching approach provides an eligible clue for fabricating porous scaffolds with high mechanical performance for use as artificial extracellular matrices.

Mechanical properties and biocompatibility of melt processed, self-reinforced ultrahigh molecular weight polyethylene.

The low efficiency of fabrication of ultrahigh molecular weight polyethylene (UHMWPE)-based artificial knee joint implants is a bottleneck problem because of its extremely high melt viscosity. We prepared melt processable UHMWPE (MP-UHMWPE) by addition of 9.8 wt% ultralow molecular weight polyethylene (ULMWPE) as a flow accelerator. More importantly, an intense shear flow was applied during injection molding of MP-UHMWPE, which on one hand, promoted the self-diffusion of UHMWPE chains, thus effectively reducing the structural defects; on the other hand, increased the overall crystallinity and induced the formation of self-reinforcing superstructure, i.e., interlocked shish-kebabs and oriented lamellae. Aside from the good biocompatibility, and the superior fatigue and wear resistance to the compression-molded UHMWPE, the injection-molded MP-UHMWPE exhibits a noteworthy enhancement in tensile properties and impact strength, where the yield strength increases to 46.3 ± 4.4 MPa with an increment of 128.0%, the ultimate tensile strength and Young's modulus rise remarkably up to 65.5 ± 5.0 MPa and 1248.7 ± 45.3 MPa, respectively, and the impact strength reaches 90.6 kJ/m(2). These results suggested such melt processed and self-reinforced UHMWPE parts hold a great application promise for use of knee joint implants, particularly for younger and more active patients. Our work sets up a new method to fabricate high-performance UHMWPE implants by tailoring the superstructure during thermoplastic processing.

Genome shuffling of Streptomyces gilvosporeus for improving natamycin production.

Improvement of natamycin production by Streptomyces gilvosporeus ATCC 13326 was performed by recursive protoplast fusion in a genome-shuffling format. After four rounds of genome shuffling, the best producer, GS 4-21, with genetic stability was obtained and its production of natamycin reached 4.69 ± 0.05 g/L in shaking flask after 96 h cultivation, which was increased by 97.1% and 379% in comparison with the highest parental strain pop-72A(r)07 and the initial strain ATCC 13326, respectively. Compared with the initial strain ATCC 13326, the recombinant GS 4-21 presented higher polymorphism. Fifty-four proteins showed differential expression levels between the recombinant GS 4-21 and initial strain ATCC 13326. Of these proteins, 34 proteins were upregulated and 20 proteins were downregulated. Of the upregulated proteins, one protein, glucokinase regulatory protein, was involved in natamycin biosynthesis. This comprehensive analysis would provide useful information for understanding the natamycin metabolic pathway in S. gilvosporeus.