Tumour-targeted drug and gene delivery: principles and concepts.
Delivery systems for tumour targeting fall into two basic categories: drug conjugate systems, in which individual drug molecules are chemically modified to target them directly to the tumour; and carrier-based systems, in which the drug or gene is first packaged non-covalently into a synthetic carrier that is then targeted to the tumour. In both cases, the objective is to maximise exposure of the target cells to the drug yet minimise side effects that result from nonspecific toxicity in normal tissues. The creation of such dose differentials is based on phenotypic differences between the tumour and the rest of the body. However, although a wide range of such changes have been linked to the transformation of normal cells to cancer cells, no single common feature exists to allow unambiguous targeting to the tumour. In addition, the tumour microenvironment creates physical barriers that significantly impair transport within the tumour. It is therefore important to match the delivery requirements of the drug to the capabilities of the delivery system. In this review, a brief overview is given of the underlying concepts and principles that help guide the development of such tumour-targeting strategies.
Cassidy
Jim
J
Centre for Oncology and Applied Pharmacology, Cancer Research UK Beatson Laboratories, Division of Cancer Sciences and Molecular Pathology, University of Glasgow, Glasgow, G61 1BD, UK. J.Cassidy@beatson.gla.ac.uk
Schätzlein
Andreas G
AG
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers; D016503:Drug Delivery Systems; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D018014:Gene Transfer Techniques; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010316:Particle Size
D000970:Antineoplastic Agents; D004337:Drug Carriers