Manipuri scientist discovers ELP based biopolymer
IMPHAL, 30th May: Dr Vijaya Sarangthem and her collaborator at Kyungpook National University, Daegu, South Korea, discovered a new Elastin-Like Polypeptides (ELP) based biopolymer that can serve as an excellent carrier of anti-cancer drugs for targeted cancer therapy with lesser side effect and organ toxicity.
The same team had recently published their findings in two research articles namely Journal of Nanobiotechnology and Nanotheranostics.
Presently, Dr Vijaya is a scientist at the Department of Pathology, AIIMS, New Delhi and she is the eldest daughter of Sarangthem Biramani Singh and Waribam Mema Devi of Wangkhei, Thambalkhong Sabal Leikai. Earlier, she had spent nine years in Kyungpook National University for her PhD in Biomedical Sciences and Post-doc.
According to information shared by Dr Vijaya on the new discovery, cancer therapy using chemotherapeutic drugs are one of the most common treatments used since past many decades. But, most of the chemotherapeutic drugs after administration distributed in all parts of the body, not just in tumor tissue. Because of this, it shows minimal effects due to the unavailability of adequate doses of drug at tumor site and undesirable side effects owing to accumulation in healthy tissues. Therefore, a novel approach to deliver anti-cancer drugs specifically to the tumor tissue sparing the normal cells is urgently required.
In the past few decades, nanomedicine has gain lots of attention due to several advantages over conventional cancer therapies. Nanomedicine provides new opportunities for early detection and diagnosis of cancer, thereby improving the treatment of cancer patients. Cancer nanomedicines can deliver the chemotherapeutic agents to tumor tissues while reducing systemic toxicity. Numerous drug delivery systems and molecular targeted therapies have been developed as an approach to solve the lack of specificity of conventional therapeutic drugs. Nanoparticle - or macromolecule - based drug carriers can be linked to the therapeutic agent covalently and target the perivascular tumor region via passive or active targeting strategies. Excessive leakiness of the tumor vasculature with large pores (cut off size ≥ 200 nm) and poor lymphatic drainage favors selective accumulation of macromolecular drug delivery systems (micelles, liposomes, etc.) in the tumor. Nowadays, FDA has approved nanoparticle-based anticancer drugs like Albumin bound Paclitaxel (Abraxane), Liposomal doxorubicin (Doxil) for the treatment of various cancers.
In the recent years, genetically engineered biopolymers like elastin-like polypeptide (ELP) have been explored as an excellent human derived bio-polymer that can be brought to clinical level with less trouble in manufactured process or cost-effective manner for targeted cancer therapy and regenerative medicine. ELPs are human tropoelastin derived polymers, which are highly biocompatible, biodegradable, non-immunogenic and hence suitable for clinical applications. The chemical and physical properties of the ELP can be precisely controlled. ELPs can be easily purified with high yield from E coli with high-purity and clinical grade materials are cheaply obtained. These ELP-based polymers can self-assemble into monodisperse drug-loaded nanoparticles and will exhibit favorable pharmacokinetics properties. Preclinical studies have shown that ELP can serve as excellent carrier for anticancer drugs like doxorubicin, paclitaxel. Till now, many ELP-based drugs are already in phase III clinical trial for the treatment of metabolic diseases like diabetes and cancer.
To enhance the selective accumulation in cancer, ELP based nanoparticles have been constructed for ideal molecular weight, size and surface characteristics to increases their stability in blood circulation. These biopolymer-based nanoparticles were designed to have multivalent presentation of tumor-specific ligands that could selectively binds with over-expressed surface receptor or antigen present on the cancer cells. Screening for ligands that specifically target these receptors represent an excellent cancer therapy strategy.
Dr Vijaya and her research team in South Korea discovered an Interleukin 4 receptor (IL-4R) binding peptide (AP1) by phage display technique. The IL-4Rs are over-expressed in various cancers like breast cancer, lung cancer, glioblastoma, ovarian cancer etc., and have been exploited for targeted therapy.
Dr Vijaya’s group first published the findings in Plos One (2013) and followed by another key publication at Theranostics (2016), where they designed an ELP based multivalent targeting polymer with tandem repeat of AP1 (highly specific IL-4R binding ligands) and the proapoptotic peptide (KLAKLAK) to kill the IL-4R expressing cancer cells. The presence of cancer specific ligands such as AP1 enhanced intratumoral accumulation limiting the systemic exposure. They have successfully shown the therapeutic effect of AP1-ELP-KLAK in various IL-4R overexpressing breast cancer, melanoma, and glioma mice modeland later published in Thernanostics (2016). In their recent publication in Nanothernostics (2020), they constructed various library of IL-4R targeting ELP biopolymer with different molecular weight and structures. These multivalent ELP-based delivery systems have excellent tumor-targeting potential and the molecular weight and structure of polypeptides play vital roles in determining tumor penetration, biodistribution, as well as retention time in tumor tissue. As IL-4R is overexpressed in different types of the solid tumor, her group believed that these AP1-ELPs would provide a promising platform for targeted therapy of various cancers. Further, these targeted ELPs platform can be used to deliver FDA approved anti-cancer drugs. The resulted pro-drugs will hold the ability to selectively kill cancer cells without affecting normal cells with a controlled release mechanism. Also, it will provide the protection of anticancer drugs after administration and allow by passing of many barriers with minimal loss of doses or activity in the blood stream. Thus, the targeted ELP platform of drug delivery will improve the patient survival and quality of life by increasing the intracellular concentration of drugs and reducing dose-limiting toxicities.
At present, Dr Vijaya’s lab is incorporating different anti-cancer drugs like paclitaxel, eribulin and doxorubicin to the ELP nanoparticles that can be used for the treatment of ovarian cancer, breast cancer and lung cancer etc.
Dr Vijaya’s research lab focused on targeted delivery of anti-cancer drugs and regenerative medicine funded by DST and ICMR.
Interested candidates willing to pursue PhD in the above area can contact at the email ID firstname.lastname@example.org@gmail.com (Dr Thoudam Debraj Singh/Dr Vijaya’s husband), Assistant Professor in Medical Oncology Lab, AIIMS, New Delhi).