Nanotechnology-Based Cancer Therapeutics—Promise and Challenge—Lessons Learned Through the NCI Alliance for Nanotechnology in Cancer

Abstract

The new generation of nanotechnology-based drug formulations is challenging the accepted ways of cancer treatment. Multi-functional nanomaterial constructs have the capability to be delivered directly to the tumor site and eradicate cancer cells selectively, while sparing healthy cells. Tailoring of the nano-construct design can result in enhanced drug efficacy at lower doses as compared to free drug treatment, wider therapeutic window, and lower side effects. Nanoparticle carriers can also address several drug delivery problems which could not be effectively solved in the past and include reduction of multi-drug resistance effects, delivery of siRNA, and penetration of the blood-brain-barrier. Although challenges in understanding toxicity, biodistribution, and paving an effective regulatory path must be met, nanoscale devices carry a formidable promise to change ways cancer is diagnosed and treated. This article summarizes current developments in nanotechnology-based drug delivery and discusses path forward in this field. The discussion is done in context of research and development occurring within the NCI Alliance for Nanotechnology in Cancer program.

Tumor Uptake of Hollow Gold Nanospheres After Intravenous and Intra-arterial Injection: PET/CT Study in a Rabbit VX2 Liver Cancer Model

“…However, use of these techniques is limited by incomplete elimination of cancer cells; therefore, there remains an urgent need to develop treatment approaches targeting liver tumors. Although recent advances in nanotechnology offer promise for selective delivery of anticancer drugs to cancer cells, efficient delivery to target sites remains challenging [4–6]. Increased drug uptake in solid tumors is often achieved by either passive targeting, via enhanced permeability and retention, or active targeting, in which a homing ligand is attached to the nanoparticles to facilitate their selective binding to tumor cells or tumor stroma.…”

Nanotechnology in the war against cancer: new arms against an old enemy – a clinical view

“…This is a major barrier to translating results from the bench to the clinic. Other technical aspects to consider in the early research phase include the stability of the constructs in solution, their stability in storage, aggregation phenomena, and associated changes in size (size alone is a major parameter determining half-life in circulation and liver and spleen uptake) [20,41,103,118]. The demands on a nanomedicine are considerably different and more numerous than for a conventional 'small molecule' drug [119].…”

“…The therapeutic possibilities of siRNA-based therapeutics are enormous if the shortcomings of low stability and localization can be avoided. A huge array of literature exist on this topic and we have highlighted a few for the interested reader[39,41,50,55,71,[94][95][96][97][98][99][100][101][102][103][104][105][106][107][108].• • Revival of discarded therapeutics…”

Blood-to-Brain Drug Delivery Using Nanocarriers

“…For all human drugs, and especially for neurotherapeutics, it is important to demonstrate safety of the drug with respect to the central nervous system (FDA 2001 ). However, governmental regulations are hindered by a lack of toxicology data for nanocarriers (Fernandes et al 2010 ;Farrell et al 2011 ). In addition, Wolf and Jones ( 2011 ) have recommended extra oversight for clinical research due to the uncertain but possibly signifi cant risks of new science and technology associated with nanomedicine (including drug nanocarriers).…”