Poly(α-L-glutamic acid) (PGA) is a class of synthetic polypeptides composed of the monomeric unit α-L-glutamic acid. Owing to their biocompatibility, biodegradability, and non-immunogenicity, PGA-based nanomaterials have been elaborately designed for drug delivery systems. Relevant studies including the latest research results on PGA-based nanomaterials for drug delivery have been discussed in this work. The following related topics are summarized as: (1) a brief description of the synthetic strategies of PGAs; (2) an elaborated presentation of the evolving applications of PGA in the areas of drug delivery, including the rational design, precise fabrication, and biological evaluation; (3) a profound discussion on the further development of PGA-based nanomaterials in drug delivery. In summary, the unique structures and superior properties enables PGA-based nanomaterials to represent as an enormous potential in biomaterials-related drug delivery areas.

Background: The bioconversion of phytosterols into high value-added steroidal intermediates, including the 9α-hydroxy-4-androstene-3,17-dione (9-OHAD) and 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC), is the cornerstone in steroid pharmaceutical industry. However, the low transportation efficiency of hydrophobic substrates into mycobacterial cells severely limits the transformation. In this study, a robust and stable modification of the cell wall in M. neoaurum strain strikingly enhanced the cell permeability for the high production of steroids. Results: The deletion of the nonessential kasB, encoding a β-ketoacyl-acyl carrier protein synthase, led to a disturbed proportion of mycolic acids (MAs), which is one of the most important components in the cell wall of Mycobacterium neoaurum ATCC 25795. The determination of cell permeability displayed about two times improvement in the kasB-deficient strain than that of the wild type M. neoaurum. Thus, the deficiency of kasB in the 9-OHAD-producing strain resulted in a significant increase of 137.7% in the yield of 9α-hydroxy-4-androstene-3,17-dione (9-OHAD). Ultimately, the 9-OHAD productivity in an industrial used resting cell system was reached 0.1135 g/L/h (10.9 g/L 9-OHAD from 20 g/L phytosterol) and the conversion time was shortened by 33%. In addition, a similar self-enhancement effect (34.5%) was realized in the 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC) producing strain. Conclusions: The modification of kasB resulted in a meaningful change in the cell wall mycolic acids. Deletion of the kasB gene remarkably improved the cell permeability, leading to a self-enhancement of the steroidal intermediate conversion. The results showed a high efficiency and feasibility of this construction strategy.

Nanomedicine is a broad field that focuses on the development of nanocarriers to deliver specific drugs to targeted sites. A synthetic polypeptide is a kind of biomaterial composed of repeating amino acid units that are linked by peptide bonds. The multiplied amphiphilicity segment of the polypeptide could assemble to form polypeptide vesicles (PVs) under suitable conditions. Different from polypeptide vesicles, outer membrane vesicles (OMVs) are spherical buds of the outer membrane filled with periplasmic content, which commonly originate from Gram-negative bacteria. Owing to their biodegradability and excellent biocompatibility, both PVs and OMVs have been utilized as carriers in delivering drugs. In this review, we discuss the recent drug delivery research based on PVs and OMVs. These related topics are presented: (1) a brief introduction to the production methods for PVs and OMVs; (2) a thorough explanation of PV- and OMV-related applications in drug delivery including the vesicle design and biological assessment; (3) finally, we conclude with a discussion on perspectives and future challenges related to the drug delivery systems of PVs and OMVs.

The development of antitumor drugs has attracted cancer researchers and the identification of novel antitumor lead compounds is certainly of great interest. The fermentation broth of Bacillus sp. N11-8, which was isolated from the Antarctic waters, showed cytotoxicity towards different cells. A cytotoxic polypeptide, PBN11-8, was purified from the fermentation broth of Bacillus sp. N11-8 using ultrafiltration, ammonium sulfate precipitation, anion exchange liquid chromatography and high performance liquid chromatography (HPLC). Cloning and sequence analysis showed that PBN11-8 polypeptide (MW: ~19 kDa by the electrospray-ionization (ESI)) displayed high similarity with peptidase M84 from Bacillus pumilus. PBN11-8 possessed moderate cytotoxicity towards several cancer cell lines with IC₅₀ values of 1.56, 1.80, 1.57, and 1.73 µg/mL against human hepatocellular carcinoma cell line BEL-7402, human renal clear cell adenocarcinoma cell line 786-0, human hepatocellular carcinoma cell line HepG2, and human pancreatic cancer cell line Panc-28, respectively. Moreover, the polypeptide displayed weak cytotoxicity towards normal cell line renal tubular epithelial cell line HK2 and human normal liver cell line L02 cells. Wound healing migration and Transwell experiments demonstrate that PBN11-8 could inhibit the migration and invasion of BEL-7402. Further investigation revealed that PBN11-8 suppresses focal adhesion kinase (FAK)-mediated adhesion, migration, and invasion by disturbing FAK/extracellular regulated protein kinases (ERK) signaling and matrix metalloproteinase-2(MMP-2) and matrix metalloproteinase-9 (MMP-9) in BEL-7402 cells. Thus, PBN11-8 represents a potential novel anti-cancer lead compound.