Aptamernanoparticle Conjugates For Targeted Cancer Therapy

Virtually every branch of medicine has been dramatically impacted by controlled drug delivery strategies during the past four decades,3,69-72 including cardiology,73 ophthalmology,74 endo-

crinology,75 oncology,76 immunology,77 and orthopedics.78 Drugs can be released in a controlled manner from within a material through surface or bulk erosion of the material, diffusion of the drug from the interior of the material, or swelling followed by diffusion or triggered by the environment

2 79 80 81

or other external events,2 such as changes in pH,'9 light,80 temperature,81 or the presence of an analyte, such as glucose.82 In general, controlled-release polymer systems deliver drugs in the optimum dosage for long periods, thus increasing the efficacy of the drug, maximizing patient compliance and enhancing the ability to use highly toxic, poorly soluble, or relatively unstable drugs.

The conjugation of aptamers to drug encapsulated nanoparticles results in targeted delivery vehicles for therapeutic application. These may include delivery of small molecule drugs, protein based drugs, nucleic acid drugs (anti-sense oligoneucleotide, RNAi or gene therapy), and targeted delivery of agents for neutron capture therapy or photodynamic therapy. Aptamers may also be bound to imaging agents to facilitate diagnosis and identification of tumor metastases. For example, it may be useful to bind aptamers to optical imaging agents including fluorophores68

83 84,85

and quantum dots (nanocrystals) or MRI imaging agents such as magnetic nanoparticles , for detection of small foci of cancer metastasis. Multiplex systems comprising drug laden nanoparticle aptamer conjugates, together with imaging agents, represent a prospective avenue to future research.

0 Chemotherapeutic O Surface functionality

Spacer group V Targeting moiety

Biodegradable polymer

FIGURE 16.2 Schematic representation of targeted drug delivery vehicle composed of polymeric nanoparticles that are surface-modified with targeting agents.

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