Nanotechnology has the potential to revolutionize cancer diagnosis and therapy. Advances in protein engineering and materials science have contributed to novel nanoscale targeting approaches that may bring new hope to cancer patients. Several therapeutic nanocarriers have been approved for clinical use. However, to date, there are only a few clinically approved nanocarriers that incorporate molecules to selectively bind and target cancer cells. This review examines some of the approved formulations and discusses the challenges in translating basic research to the clinic. We detail the arsenal of nanocarriers and molecules available for selective tumour targeting, and emphasize the challenges in cancer treatment.

Nanocarriers as an emerging platform for cancer therapy

Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review.

Alginate: properties and biomedical applications

We describe the development of multifunctional nanoparticle probes based on semiconductor quantum dots (QDs) for cancer targeting and imaging in living animals. The structural design involves encapsulating luminescent QDs with an ABC triblock copolymer and linking this amphiphilic polymer to tumor-targeting ligands and drug-delivery functionalities. In vivo targeting studies of human prostate cancer growing in nude mice indicate that the QD probes accumulate at tumors both by the enhanced permeability and retention of tumor sites and by antibody binding to cancer-specific cell surface biomarkers. Using both subcutaneous injection of QD-tagged cancer cells and systemic injection of multifunctional QD probes, we have achieved sensitive and multicolor fluorescence imaging of cancer cells under in vivo conditions. We have also integrated a whole-body macro-illumination system with wavelength-resolved spectral imaging for efficient background removal and precise delineation of weak spectral signatures. These results raise new possibilities for ultrasensitive and multiplexed imaging of molecular targets in vivo.

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In vivo cancer targeting and imaging with semiconductor quantum dots

Hydrogels for tissue engineering.

Controlled release technologies : a survey of research and commercial applications

Poly(amido-amines) (PAAs) are synthetic polymers characterized by the presence of amido and tertiary amino groups regularly arranged along their macromolecular chain. Therefore, they can be classified as polycations.

Tailor-made soluble polymer carriers

Stability of antisense oligonucleotides during incubation with a mixture of isolated lysosomal enzymes

The plant alkaloid emetine has considerable potential as an antitumor agent, but early attempts to develop the compound clinically failed due to unacceptable dose limiting toxicity and poorly reproducible results. This study reports the synthesis and characterization of novel N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates containing emetine. The drug was linked to the polymer via biodegradable (Gly-Phe-Leu-Gly) and non-degradable (Gly-Gly) peptidyl linkers. HPMA-Gly-Gly emetine conjugate was found to contain 8% (w/w) of bound emetine, while emetine loading of HPMA-Gly-Phe-Leu-Gly-emetine was found to be 19% (w/w). Due to the change in cellular pharmacokinetics, polymer conjugates are invariably less toxic than free drug, in vitro and HPMA copolymer-emetine conjugates were no exception. Conjugates containing the biodegradable Gly-Phe-Leu-Gly linker displayed an IC50 of 90 μg/mL towards L1210 leukemia cells which is 225 less toxic than free emetine (IC50 = 0.4 μg/mL). Against B16F10 melanoma ...

Synthesis and Characterization of N-(2-Hydroxypropyl)-Methacrylamide (HPMA) Copolymer-Emetine Conjugates:

Soluble synthetic polymers have potential as targetable drug delivery and release agents. Copolymers of 2-hydroxypropylmethacrylamide with oligopeptide side-chains have been used to demonstrate the attachment of drug analogues by covalent linkages susceptible to hydrolysis by lysosomal enzymes but stable in plasma. Targeting of polymers to particular sites has been illustrated by making use of the substrate specificity of adsorptive pinocytosis.

Ruth Duncan

Papers

Controlled release technologies : a survey of research and commercial applications

Tailor-made soluble polymer carriers

Stability of antisense oligonucleotides during incubation with a mixture of isolated lysosomal enzymes

Synthesis and Characterization of N-(2-Hydroxypropyl)-Methacrylamide (HPMA) Copolymer-Emetine Conjugates:

Soluble synthetic polymers as targetable agents for intracellular drug release