β-poly-l-malic acid (pmla) is a natural polyester with excellent water solubility that can be produced by a variety of microorganisms. PmLA is naturally available and, given its excellent biosavailability, bioavailability, biocompatibility and biodegradability, can be used as an ideal carrier for a variety of molecules, including nucleotides, proteins, chemotherapeutic drugs and imaging agents. At present, PMLA has been successfully applied to medical research on drug delivery and biological imaging for cancer treatment.
Recently, the research group of Professor Liang Guoxin of China Medical University and the research group of Professors Tao Zhimin and Xu Wenrong of Jiangsu University School of Medicine published an article in the journal hopes biochem sci biosynthetic polymalic acid as a delivery nanoplatform for translational cancer medicine. For the first time, the biological characteristics, physicochemical properties, unique synthesis mechanism and latest medical translational research results of pmla as a nanoscale natural polymer delivery carrier are systematically expounded, especially the latest transformational application of pmla in improving the diagnosis and treatment effect of tumors. Biomanufactured PMLA is expected to be used as an ideal carrier for anti-tumor drugs in tumor treatment, with broad application prospects. The systematic elaboration of PMLA in this paper provides a new idea for the precision targeted treatment of tumors, which has important reference value.
PMLA is widely studied as a nano-platform for tumor diagnosis and treatment, and through step-by-step chemical synthesis, PMLA can be directly coupled or further modified by the lignette molecule, so as to connect with a variety of biological ligands and play different physiological roles. Recently, researchers have conducted preclinical studies on its use as a drug carrier. The results of an animal study showed that these PMLA-based nanoconjugates can effectively pass through the blood-brain and blood-tumor barriers, thereby visualizing cancerous lesions and releasing drugs to inhibit tumor neovascularization, making it promising to be applied as a novel route of administration in the treatment of nervous system tumors. There have also been studies that combine PMLA with different antibody drugs, penetrating peptides, and fluorescent or magnetic contrast agents to produce different biopolymers and show better targeting and accumulation in specific tumors, such as breast tumors and nervous system tumors.
The biomanufactured PMLA itself is able to bind to and transport molecules to nuclear proteins associated with DNA replication as molecular transporters, playing an important role in maintaining protein homeostasis and assisting in DNA synthesis. While maintaining water solubility, pmla has not yet found clear biological toxicity and immunogenicity. The molecule is rich in carboxyl groups, is chemically active, and has a high ability to bind hydrophobic molecules, making it compatible with a variety of biological systems. A number of recent research results show that pmla has most of the characteristics required for carrier substances, not only has the advantages of low toxicity and sustainable production, but also has strong bioavailability, biocompatibility and biodegradability, and even can pass through the blood-brain barrier, so that it has a huge advantage in solving the complex cancer problem compared to many other drug delivery systems, highlighting its great potential in clinical translation.
As a nano platform for cancer diagnosis and treatment, pmla has broad application prospects. However, due to its low yield, high cost, and difficulty in determining or controlling the length of the biopolymers produced, microbial production of PMLA remains a challenge at present. Future research directions are how to use gene editing techniques to make foreign gene sequences more efficiently introduced into cells, or to produce PMLA in a controlled manner by using new gene editing tools that pre-select high-yield strains, thereby predetermining their molecular weight and increasing their yield.
Original link:
https://www.cell.com/trends/biochemical-sciences/fulltext/s0968-0004(20)30244-9