Nanotechnology has the potential to revolutionize cancer diagnosis and therapy. Advances in protein engineering and materials science have contributed to novel nanoscale targeting approaches that may bring new hope to cancer patients. Several therapeutic nanocarriers have been approved for clinical use. However, to date, there are only a few clinically approved nanocarriers that incorporate molecules to selectively bind and target cancer cells. This review examines some of the approved formulations and discusses the challenges in translating basic research to the clinic. We detail the arsenal of nanocarriers and molecules available for selective tumour targeting, and emphasize the challenges in cancer treatment.

Nanocarriers as an emerging platform for cancer therapy

Nanocrystals are fundamental to modern science and technology. Mastery over the shape of a nanocrystal enables control of its properties and enhancement of its usefulness for a given application. Our aim is to present a comprehensive review of current research activities that center on the shape-controlled synthesis of metal nanocrystals. We begin with a brief introduction to nucleation and growth within the context of metal nanocrystal synthesis, followed by a discussion of the possible shapes that a metal nanocrystal might take under different conditions. We then focus on a variety of experimental parameters that have been explored to manipulate the nucleation and growth of metal nanocrystals in solution-phase syntheses in an effort to generate specific shapes. We then elaborate on these approaches by selecting examples in which there is already reasonable understanding for the observed shape control or at least the protocols have proven to be reproducible and controllable. Finally, we highlight a number of applications that have been enabled and/or enhanced by the shape-controlled synthesis of metal nanocrystals. We conclude this article with personal perspectives on the directions toward which future research in this field might take.

Shape‐Controlled Synthesis of Metal Nanocrystals: Simple Chemistry Meets Complex Physics?

Hollow micro-/nanostructures are of great interest in many current and emerging areas of technology. Perhaps the best-known example of the former is the use of fly-ash hollow particles generated from coal power plants as partial replacement for Portland cement, to produce concrete with enhanced strength and durability. This review is devoted to the progress made in the last decade in synthesis and applications of hollow micro-/nanostructures. We present a comprehensive overview of synthetic strategies for hollow structures. These strategies are broadly categorized into four themes, which include well-established approaches, such as conventional hard-templating and soft-templating methods, as well as newly emerging methods based on sacrificial templating and template-free synthesis. Success in each has inspired multiple variations that continue to drive the rapid evolution of the field. The Review therefore focuses on the fundamentals of each process, pointing out advantages and disadvantages where appropriate. Strategies for generating more complex hollow structures, such as rattle-type and nonspherical hollow structures, are also discussed. Applications of hollow structures in lithium batteries, catalysis and sensing, and biomedical applications are reviewed.

Hollow Micro-/Nanostructures: Synthesis and Applications**

Gold nanoparticles have been used in biomedical applications since their first colloidal syntheses more than three centuries ago. However, over the past two decades, their beautiful colors and unique electronic properties have also attracted tremendous attention due to their historical applications in art and ancient medicine and current applications in enhanced optoelectronics and photovoltaics. In spite of their modest alchemical beginnings, gold nanoparticles exhibit physical properties that are truly different from both small molecules and bulk materials, as well as from other nanoscale particles. Their unique combination of properties is just beginning to be fully realized in range of medical diagnostic and therapeutic applications. This critical review will provide insights into the design, synthesis, functionalization, and applications of these artificial molecules in biomedicine and discuss their tailored interactions with biological systems to achieve improved patient health. Further, we provide a survey of the rapidly expanding body of literature on this topic and argue that gold nanotechnology-enabled biomedicine is not simply an act of ‘gilding the (nanomedicinal) lily’, but that a new ‘Golden Age’ of biomedical nanotechnology is truly upon us. Moving forward, the most challenging nanoscience ahead of us will be to find new chemical and physical methods of functionalizing gold nanoparticles with compounds that can promote efficient binding, clearance, and biocompatibility and to assess their safety to other biological systems and their long-term term effects on human health and reproduction (472 references).

The golden age: gold nanoparticles for biomedicine

Colloidal metal nanoparticles are emerging as key materials for catalysis, plasmonics, sensing, and spectroscopy. Within these applications, control of nanoparticle shape lends increasing functionality and selectivity. Shape-controlled nanocrystals possess well-defined surfaces and morphologies because their nucleation and growth are controlled at the atomic level. An overall picture of shaped metal particles is presented, with a particular focus on solution-based syntheses for the noble metals. General strategies for synthetic control are discussed, emphasizing key factors that result in anisotropic, nonspherical growth such as crystallographically selective adsorbates and seeding processes.

/pdf/shape-control-of-colloidal-metal-nanocrystals-33lclmees7.pdf

Shape Control of Colloidal Metal Nanocrystals

Gold nanocages of <40 nm in dimension have been synthesized using the galvanic replacement reaction between Ag nanocubes and HAuCl4 in an aqueous solution. By controlling the molar ratio between Ag and HAuCl4, the gold nanocages could be tuned to display surface plasmon resonance peaks around 800 nm, a wavelength commonly used in optical coherence tomography (OCT) imaging. OCT measurements on phantom samples indicate that these gold nanocages have a moderate scattering cross-section of ∼8.10 × 10-16 m2 but a very large absorption cross-section of ∼7.26 × 10-15 m2, suggesting their potential use as a new class of contrast agents for optical imaging. When bioconjugated with antibodies, the gold nanocages have also been demonstrated for specific targeting of breast cancer cells.

Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents.

This paper reports on our recent development of two-types of all-fiber-optic scanning endomicroscopy technologies for high-resolution optical imaging of internal organs. The first one is an OCT balloon catheter technology that permits systematic imaging of fine architectural morphologies of internal luminal organs over a large area. The second is a two-photon fluorescence endomicroscopy technology that enables assessment of tissue biochemical/metabolic information with a superb spatial resolution. Both endomicroscopes have a small diameter (1.2–2.4 mm) and can be readily integrated with a standard clinical gastroscope, providing complementary information about tissue structure and function and helping improve diagnostic yield. We will discuss the basic design principles, major engineering challenges, solutions, and some preliminary results. In addition, we will also present our approach in developing near infrared (NIR) fluorescent nanocomplexes (ICG-micelles), which can be functionalized for active molecular targeting to improve molecular specificity and imaging contrast. These nanocomplexes, made of FDA approved building blocks, are biocompatible and very promising for clinical translation. Ultimately the NIR nanocomplexes can be used in conjunction with endomicroscopy technologies for performing high-resolution optical molecular imaging in vivo and in real time.

Michael J. Cobb

Papers

Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents.

Endomicroscopy and biocompatible fluorescent nanocomplexes for clinical translation of high-resolution optical molecular imaging