Anti-Tumour Polymer Conjugate

Anti-Tumour Polymer Conjugate


Cancer kills more people every year than AIDS, tuberculosis, and malaria combined. According to the Union for International Cancer Control (UICC), over 7 million people die from cancer every year, and more than 11 million new cases are diagnosed worldwide. Furthermore, if current trends are to continue, new cases of cancer will increase to 16 million per year by 2020, with 10 million associated deaths. Treatments are available for cancer, most notably chemotherapies, which are well known to be transiently effective with median survival periods of about 2 years. This is largely because chemotherapies that are based on alkylating agents, antimetabolites and natural products are heterogeneous in their mode of action, and most of them also act against normal mammalian cells, consequently causing severe side effects. The non-selective nature of these drugs is responsible for the significantly reduced survival rates, but even when incorporated into a drug delivery system, chemotherapy drugs often have deleterious side-effects caused by inadvertent drug-induced damage to healthy cells and tissue. The need for chemotherapy drugs to penetrate into the target cells in order to function results in the cells developing resistance and they pump the drugs out using multi-drug resistant proteins and make cellular changes that include an increased expression of drug detoxifying enzymes.

Tyrothricin, a mixture of cyclic decapeptides (tyrocidine, tryptocidine, phenycidine etc.) is a natural antibiotic compound produced by a soil bacterium (Bacillus aneurinolyticus). Tyrothricin was the first antibiotic to be used in clinical practices, but later fell into disrepute due to its haemolytic and eukaryotic cell toxicity and now has only limited topical applications. In 2007, Stellenbosch Professor Marina Rautenbach and colleagues published a promising investigation into the antimalarial properties of tyrocidine peptides against P. falciparum infected blood cells. In addition they were shown to be active against prostate cancer immortal cell lines.

Tyrothricin, tyrocidines and the aforementioned members of the cyclic decapeptide group lyse healthy red blood cells and other cells, even at micromolar peptide concentrations. They are therefore toxic on their own, especially in a systemic method of treatment. However, researchers at Stellenbosch University discovered that having been conjugated to a polymer system, the peptides are rendered non-toxic and inactive. The key to reactivating these peptides lies in active targeting and triggered release. The released peptides become toxic again enabling localised damage to cancerous cells without leading to chemotherapeutic system toxicity in the patient.


Medical field, specifically the pharmaceutical industry


Apart from the benefits that come with the polymers of N-Vinylpyrrolidone like low toxicity, biocompatibility and resistance to hydrolysis in aqueous media, tyrocidines conjugated to the polymer and targeting moiety in a method described by this invention result only in localised trauma and still allows for degradation by proteolytic enzymes with low chemical fall out.


Many chemotherapy drugs are poorly soluble in aqueous media thus limiting their ability to reach the internalised target cells. The result is low bioavailability and poor pharmacokinetics and at the same time gives rise to non-specific drug delivery and toxicity. To achieve high therapeutic indices using these methods, high dosage is required. According to the method described in this invention, very low concentration of the therapeutic agent is required because the drug delivery construct is equipped with small molecule ligands with high affinity for membrane proteins at the tumour cells thus delivering the payload to the precise location


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