|LETTER TO THE EDITOR
|Year : 2015 | Volume
| Issue : 2 | Page : 494-495
Role of polyhydroxyalkanoates in cancer and other drug delivery systems
Roopesh Jain, Archana Tiwari
School of Biotechnology, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Gandhi Nagar, Bhopal, Madhya Pradesh, India
|Date of Web Publication||7-Jul-2015|
School of Biotechnology, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Airport Bypass Road, Gandhi Nagar, Bhopal, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Jain R, Tiwari A. Role of polyhydroxyalkanoates in cancer and other drug delivery systems. J Can Res Ther 2015;11:494-5
Polyhydroxyalkanoates (PHAs), a family of biopolyesters with diverse structures, are the only bioplastics completely synthesized by microorganisms seems to be a solution for the problem pertaining to the resistance of synthetic polymers to biodegradation and their persistence in soil environment. Biopolymers produced from microorganisms or from plants are likely to replace currently used synthetic polymers as plastics.  Known examples include several PHAs, including poly 3-hydroxybutyrate (PHB), copolymers of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV), poly 4-hydroxybutyrate (P4HB), copolymers of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx) and poly 3-hydroxyoctanoate (PHO) etc. PHAs have been intensively studied in targeted drug delivery systems as a vector for targeting drugs, particularly for one of the biggest medical challenge, cancer.
A step ahead research at Multidisciplinary Research Center, Shantou University on the assessment of the risks of carcinogenicity associated with PHAs through an analysis of deoxyribonucleic acid (DNA) aneuploid and telomerase activity clearly indicate that PHA family members could be used to support cell growth without indication of susceptibility to tumor induction.  These results are important for promoting the application of PHAs as safe biomaterials for biomedical uses.
In recent years many researches have shown that PHA is an attractive polymer for its use in effective drug delivery in cancer therapy and also as medical implants, due to its biodegradability and nontoxic properties. Researcher in Ireland studied anticancer activity of a cationic antimicrobial peptide derived from monomers of PHA. 
PHAs being a family of biodegradable, nontoxic, biocompatible polyesters can be used as a nonspecific immobilizing matrix for protein presentation. A receptor-mediated, drug-specific delivery system has been reported by scientists, based on the PHA granule binding protein-PhaP. Recombinant protein fusion with PHA granule binding protein (also known as phasins) can be immobilized on the surface of PHA nanoparticles through hydrophobic interactions between PhaP and PHA, and therefore provides a low-cost protein presenting strategy.
An experimental article published in "Biomaterial", described how a receptor-mediated drug delivery system that consists of PHA nanoparticles, PhaP, and polypeptide or protein ligands fused to PhaP was developed. PhaP fused with ligands were produced by overexpression of their corresponding genes in recombinant microorganisms. Transplantable murine hepatoma22 model cells were used to evaluate the in vivo targeting effects of novel delivery systems, whereas macrophages and hepatocellular carcinoma cell Bel7402 were used to investigate the in vitro specific targeting of the ligand coated nanoparticles, respectively. Furthermore, the ligand-PhaP-PHA nanoparticle specific drug delivery system was proven effectively both in vitro and in vivo. 
In another research in China, researchers focused on costimulation of T cells via costimulatory molecules such as B7 (important for eliciting cell-mediated antitumor immunity). They studied heterologous expression of human costimulatory molecule B7-2 and construction of B7-2 immobilized PHA nanoparticles for use as an immune activation agent. In this study, the extracellular domain of the B7-2 molecule was fused with PhaP at its N-terminal and heterogeneously expressed in recombinant E. coli strain BL21 (DE3). The purified B7-2-PhaP protein was immobilized on the surface of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)-based nanoparticles. Immobilized B7-2-PhaP on PHBHHx nanoparticles provided costimulation signals to induce T cell activation and proliferation in vitro. 
Being a biocompatible material PHA is a significant candidate in drug research including implantable tissue engineering material for hard tissue replacement, regeneration, wound healing, and controlled drug release.
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