Roadmap on nanomedicine

Abstract

Since the launch of the Alliance for Nanotechnology in Cancer by the National Cancer Institute in late 2004, several similar initiatives have been promoted all over the globe with the intention of advancing the diagnosis, treatment and prevention of cancer in the wake of nanoscience and nanotechnology. All this has encouraged scientists with diverse backgrounds to team up with one another, learn from each other, and generate new knowledge at the interface between engineering, physics, chemistry and biomedical sciences. Importantly, this new knowledge has been wisely channeled towards the development of novel diagnostic, imaging and therapeutic nanosystems, many of which are currently at different stages of clinical development. This roadmap collects eight brief articles elaborating on the interaction of nanomedicines with human biology; the biomedical and clinical applications of nanomedicines; and the importance of patient stratification in the development of future nanomedicines. The first article reports on the role of geometry and mechanical properties in nanomedicine rational design; the second articulates on the interaction of nanomedicines with cells of the immune system; and the third deals with exploiting endogenous molecules, such as albumin, to carry therapeutic agents. The second group of articles highlights the successful application of nanomedicines in the treatment of cancer with the optimal delivery of nucleic acids, diabetes with the sustained and controlled release of insulin, stroke by using thrombolytic particles, and atherosclerosis with the development of targeted nanoparticles. Finally, the last contribution comments on how nanomedicine and theranostics could play a pivotal role in the development of personalized medicines. As this roadmap cannot cover the massive extent of development of nanomedicine over the past 15 years, only a few major achievements are highlighted as the field progressively matures from the initial hype to the consolidation phase.

Figure 1. Discoidal Polymeric Nanoconstructs in Cancer.

(A) Representative intravital microscopy images of 1 μm soft and rigid DPNs (red dots) in the liver of Tie2 mice (green fluorescence – endothelium; blue fluorescence – immune cells). (B) Quantification for the soft and rigid DPN accumulation in the liver vasculature and in Kupffer cells. (C) Representative intravital microscopy images of 1 μm soft and rigid DPNs (red dots) in the tumor vasculature of Tie2 mice (green fluorescence – endothelium; blue fluorescence – immune cells). Scale bars: 20 μm. (D) Quantification for the soft and rigid DPN accumulation in the tumor vasculature. (Reprinted (adapted) with permission from Key, J., et al., Soft Discoidal Polymeric Nanoconstructs Resist Macrophage Uptake and Enhance Vascular Targeting in Tumors. ACS Nano, 2015. 9(12): p. 11628-11641. Copyright (2015) American Chemical Society).

Figure 1. An explorative complement roadmap to guide future nanomedicine research and development.

Figure 1. Schematic representation of multifunctional biomolecular drug designs composed of albumin (red) and functional molecule (blue, red and green spheres) bearing oligonucleotide modules based on double stranded (A) or nanoscaffold (B) assemblies.

Figure 1. Schematic illustration of EPR based delivery of NCs. NCs can deliver drugs and imaging agents (represented by a green star bound to the monoclonal antibodies that decorate the NCs) to tumors.

Figure 1. Major challenges and corresponding advances to meet these challenges in insulin delivery.

Figure 1

A clot or an embolus blocks the flow of blood in the brain leading to an ischemic stroke (left). Treatment via a thrombolytic nanomedicine can localize a clot busting drug at the occlusion site allowing efficient on target restoration of blood flow (right) while minimizing off-target side effects, such as: brain haemorrhage.

Figure 1

Search on Medline performed on August 2019 with “Nanomedicine” as keyword gives more than 25,000 references. We found 1336 references for “Nanomedicine & Cardiovascular”, and only 211 for “Nanomedicine & Atherosclerosis”. Results obtained each year in each category are presented from 2005.

Figure 2

The evolution of blood vessels to the atheroma will lead to coronary artery diseases (CAD) or cerebrovascular diseases in the brain (stroke). 85% of CVD deaths are due to heart attack and stroke. New nanodiagnostics/therapies are required to improve the management of these cardiovascular diseases.

Figure 1. Patient stratification in cancer nanomedicine.

Various tools and technologies can be conceived to enable patient stratification in cancer nanomedicine clinical trials. These include liquid biomarkers (e.g. circulating tumor cells and cytokines), tissue biomarkers (e.g. vessel and macrophage density) and imaging biomarkers. The latter can encompass standard imaging probes and protocols to noninvasively and quantitatively assess tumor blood vessel perfusion and permeability, as well as companion nanodiagnostics (e.g. iron oxide nanoparticles) and nanotheranostics (e.g. radionuclide and drug co-loaded liposomes). The overall goal of including such probes and protocols for patient stratification is to differentiate between individuals who are likely to respond to such targeted therapies and individuals who are unlikely to respond, thereby contributing to nanomedicine performance, translation and product development.