Multifunctional Nanoscale Platforms for Targeting of the Cancer Cell Immortality Spectrum

Abstract

In the post-genomic era, "omics" platforms and cancer systems biology are greatly advancing our knowledge of the molecular and cellular underpinnings of cancer. In this article, we begin by outlining the factors governing the development of cancer (tumorigenesis) and use this framework to motivate the need for systems-approaches to cancer diagnostics and therapeutics. We review recent efforts to tap into the remarkable potential of nanotechnology for (i) systems-surveillance (or "sensing") of the molecular signatures of tumorigenesis, and (ii) spatiotemporally-regulated delivery (or "targeting") of combination therapeutics to cancer cells. Specifically, we highlight the salient role of polymeric biomaterials and describe the physicochemical characteristics that render them attractive for the design of such nanoscale platforms. We conclude with discussions on the emerging role of macromolecular biophysics and computational nanotechnology in engineering spatiotemporally-regulated anti-cancer systems.

Multimodal delivery of irinotecan from microparticles with two distinct compartments

“…First formulations have been evaluated in clinical trials and some have already been turned into pharmaceutical products [7,8]. While these early formulations have demonstrated the clinical potential of prolonged release formulations, these carriers are still far from optimal and lack important aspects, such as tailored release kinetics [9]. Another concern is that, as delivery carriers become more efficient in increasing local therapeutic concentrations, the risks associated with the unsolved issue of cellular drug resistance can arguably be elevated [10,11].…”

“…If chosen carefully, such carrier systems would also benefit from possible synergistic effects of the drugs that can further enhance the therapeutic efficacy of the combined delivery [13,14]. Several researchers have proposed possible strategies for the incorporation of complex release profiles in carrier systems, some of which include the use of stimuli responsive material for on-demand and complex release kinetics [9,15–18]. Responsive material can be highly sensitive to external stimuli such as pH, temperature, light, and oxidative stress [18].…”

“…The challenge in developing such delivery systems has shifted towards the design and preparation of the ideal carrier particles that can spatioselectively encapsulate separate therapeutics and release them with distinct pharmacokinetics [9]. Current carrier systems that are loaded with multiple therapeutics in a single isotropic particle lack this characteristic and may even promote antagonistic cross-interactions between drugs [9,20–22].…”

Convergence of Nanotechnology and Cancer Prevention: Are We There Yet?

“…This is likely to require modification of probes that selectively identify specific premalignant lesions. Ideally, we will be able personalize theranostic approaches and nanotarget premalignancies by implementing “-omics” approaches for profiling as a first step and selective targeting as a second step (157-159). Some recent advances in theranostics incorporate magnetic resonance imaging for early detection along with targeting (160, 161).…”

Novel Drug Therapies and Diagnostics for Personalized Medicine and Nanomedicine in Genome Science, Nanoscience, and Molecular Engineering

“…Another approach in nanomedicine utilizes computer-based methods and critical experiments to establish a variety of software tools to tackle nanometer-scale aspects of material behavior [8]. The main advantage of this computational nanotechnology approach is to increase the confidence that new nanometer-scale materials will possess the desired properties.…”