Progress in the field of precision medicine has changed the landscape of cancer therapy. Precision medicine is propelled by technologies that enable molecular profiling, genomic analysis and optimized drug design to tailor treatments for individual patients. Although precision medicines have resulted in some clinical successes, the use of many potential therapeutics has been hindered by pharmacological issues, including toxicities and drug resistance. Drug delivery materials and approaches have now advanced to a point where they can enable the modulation of a drug’s pharmacological parameters, without compromising the desired effect on molecular targets. Specifically, they can modulate a drug’s pharmacokinetics, stability, absorption and exposure to tumours and healthy tissues, and facilitate the administration of synergistic drug combinations. This Review highlights recent progress in precision therapeutics and drug delivery, and identifies opportunities for strategies to improve the therapeutic index of cancer drugs and, consequently, clinical outcomes. Precision medicine identifies the optimal treatment strategy for an individual patient. Such personalized therapies can be greatly improved by targeted drug delivery approaches. This Review investigates the integration of targeted drugs, in particular, kinase inhibitors, with targeted drug delivery systems.

Targeted drug delivery strategies for precision medicines

Kidneys are a major organ for blood filtration and waste elimination and thus play a key role in the transport and clearance of nanoparticles in vivo. The interactions of nanoparticles with different kidney compartments can be precisely regulated by modulating their size, shape and surface chemistry. The quantitative understanding of nanoparticle–kidney interactions at the molecular level is important for improving disease targeting, precisely controlling nanoparticle transport and clearance, and minimizing the potential health hazards of nanomedicines. In this Review, we summarize the glomerular filtration of macromolecules and nanoparticles in the kidney and survey kidney imaging techniques for the study of nanoparticle–kidney interactions ex vivo and in vivo. We investigate the different transport mechanisms of nanoparticles in the kidneys and discuss size, charge and shape dependencies in renal clearance. Nanoparticles are then investigated for the preclinical and clinical detection and treatment of diseases such as kidney dysfunction and cancer. Finally, challenges and opportunities for renal-clearable nanoparticles are highlighted. Interactions of nanoparticles with the kidneys affect their transport, clearance, targeting, therapeutic efficacy and biosafety in the body. This Review discusses nano–bio interactions of nanoparticles in the kidneys and highlights their potential for the detection and treatment of disease.

Transport and interactions of nanoparticles in the kidneys

What to measure? is a key question in nanoscience, and it is not straightforward to address as different physicochemical properties define a nanoparticle sample. Most prominent among these properties are size, shape, surface charge, and porosity. Today researchers have an unprecedented variety of measurement techniques at their disposal to assign precise numerical values to those parameters. However, methods based on different physical principles probe different aspects, not only of the particles themselves, but also of their preparation history and their environment at the time of measurement. Understanding these connections can be of great value for interpreting characterization results and ultimately controlling the nanoparticle structure-function relationship. Here, the current techniques that enable the precise measurement of these fundamental nanoparticle properties are presented and their practical advantages and disadvantages are discussed. Some recommendations of how the physicochemical parameters of nanoparticles should be investigated and how to fully characterize these properties in different environments according to the intended nanoparticle use are proposed. The intention is to improve comparability of nanoparticle properties and performance to ensure the successful transfer of scientific knowledge to industrial real-world applications.

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Nanoparticle Characterization: What to Measure?

Effect of physicochemical and surface properties on in vivo fate of drug nanocarriers.

There is growing need for a safe, efficient, specific and non-pathogenic means for delivery of gene therapy materials. Nanomaterials for nucleic acid delivery offer an unprecedented opportunity to overcome these drawbacks; owing to their tunability with diverse physico-chemical properties, they can readily be functionalized with any type of biomolecules/moieties for selective targeting. Nucleic acid therapeutics such as antisense DNA, mRNA, small interfering RNA (siRNA) or microRNA (miRNA) have been widely explored to modulate DNA or RNA expression Strikingly, gene therapies combined with nanoscale delivery systems have broadened the therapeutic and biomedical applications of these molecules, such as bioanalysis, gene silencing, protein replacement and vaccines. Here, we overview how to design smart nucleic acid delivery methods, which provide functionality and efficacy in the layout of molecular diagnostics and therapeutic systems. It is crucial to outline some of the general design considerations of nucleic acid delivery nanoparticles, their extraordinary properties and the structure–function relationships of these nanomaterials with biological systems and diseased cells and tissues. In this Primer, Conde and colleagues explain how to design smart nucleic acid delivery methods, which provide functionality and efficacy in the layout of molecular diagnostics and therapeutic systems. 

/pdf/nanodelivery-of-nucleic-acids-2d1fqs6w.pdf

Nanodelivery of nucleic acids

Surface chemistry plays a deciding role in nanoparticle biodistribution, yet very little is known about how surface chemistry influences the suborgan distributions of nanomaterials. Here, using quantitative imaging based on laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), we demonstrate that surface charge dictates the suborgan distributions of nanoparticles in the kidney, liver, and spleen of mice intravenously injected with functionalized gold nanoparticles. Images of the kidney show that positively charged nanoparticles accumulate extensively in the glomeruli, the initial stage in filtering for the nephron, suggesting that these nanoparticles may be filtered by the kidney at a different rate than the neutral or negatively charged nanoparticles. We find that positively and negatively charged nanoparticles accumulate extensively in the red pulp of the spleen. In contrast, uncharged nanoparticles accumulate in the white pulp and marginal zone of the spleen to a greater extent than ...

Surface Charge Controls the Suborgan Biodistributions of Gold Nanoparticles

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Surface Charge Controls the Suborgan Biodistributions of Gold Nanoparticles