Nano-Enabled Medical Applications

Lajos P. Balogh

• Publisher: Jenny Stanford Publishing
• Year: 2020
• ISBN:
  9780429677892
• Edition: 1
• Topic: Medicine
• Subtopic: Biotechnology in Medicine

This book is the second in a series presenting articles that received the most citations in recent years in nanomedicine. The series is edited by, a prominent nanotechnology researcher and editor-in-chief of Precision Nanomedicine. The theme of the second volume is about nano-enabled medical applications. The 19 articles collected here have already acquired more than 12, 500 citations highlighting the importance and professional recognition of the work of these scientists in nanomedicine. The content includes the general overview of the field and a wide variety of applications that have been impossible without nanoscience and nanotechnology.

Chapter 1
Intelligent Nanomaterials for Medicine: Carrier Platforms and Targeting Strategies—State of the Art

Georgette B. Salieb-Beugelaar,^{a, b} MarcWolf,^a Roman Lehner,^c Kegang Liu,^a Stephan Marsch,^d and Patrick Hunziker^{a, b, d}

^aNanomedicine Research Lab CLINAM, University of Basel, University Hospital Basel, Bernoullistrasse 20, CH-4056 Basel, Switzerland

^bThe European Foundation for Clinical Nanomedicine (CLINAM) Alemannengasse 12, CH-4016 Basel, Switzerland

^cAdolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, 1700 Fribourg, Switzerland

^dIntensive Care Clinic, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
[email protected]

Nanoscience and nanotechnology have been significant drivers of medical knowledge generation and medical diagnostics and are bringing new therapeutic options to many medical fields. Intelligent nanomaterials have evolved from simpler nanosized materials such as liposomes and inorganic nanoparticles; they add environmental or remote sensing, switching, and stimuli-triggered activities to the carrier functionality of basic nanomaterials. This review examines properties and requirements for such nanodelivery platforms to deploy intelligent functionality, in particular for targeting receptors, cells, and tissues, for control of their nanobio interaction, and for their utility for clinical applications. Emphasis is placed on specific carrier platforms and targeting strategies required for real-world application, extending an earlier review with up-to-date information. Advantages and challenges to intelligent nanomaterials in a clinical context, including the important notion of particle-associated toxicity, e.g., due to their PEG content are discussed.

1.1 Introduction

During the past decade, the application of nanomaterials in medicine has extended to many new directions spanning from fundamental research (e.g., crossing biological barriers in drug delivery) to (commercially available) diagnostic tests, and nanotherapeutics. These developments have a profound impact on preclinical and clinical progress and shape the scientific field of nanomedicine. Currently, some of these developments are on the market, while many are being tested in clinical trials. Multi-functional, composite nanocarriers, such as nanotheranostics are a platform that combines the use of composite nanosystems for diagnosis and therapy. Such nanosystems often consist of (i) a carrier platform, (ii) a payload for imaging, sensing, or therapy, and (iii) optional targeting ligands. Beyond such basic systems, the large freedom in design allows to compose nanosystems with complex functionality that pave the way to intelligent and responsive behavior, potentially applicable in medicine. A typical example of such platforms are nanoparticles (NPs, diameter 1–200 nm) that have already been tested for medical applications as drug delivery platforms, e.g., for cancer therapy, but also as reagent in (rapid) diagnostic tests. NPs can carry different payloads such as small molecular drugs, imaging agents, proteins, nucleic acids, and other contents [1–4]. Nanocarriers are designed to improve efficacy and safety for drug delivery in general and for target specific non-viral drug delivery in particular [5, 6]. The design of such nanomaterials requires the ability to control particle size and shape, to assure biocompatibility and stealth properties, to optimize specificity, and to achieve controlled release and functionality [7, 10]. As basic materials, liposomes, dendrimers, polymers, carbon nanotubes, metallic NPs, silica NPs, organic NPs, quantum dots, nanogels, and peptidic NPs have been applied as possible nanotechnological carrier platforms (Fig. 1.1). With an emphasis on medical therapy, this review aims to shed light on design principles suited to create complex nanosystems by combining carrier platforms, engineering nanomaterial–cell interactions and enabling such systems to show stimuli responsiveness by equipping them with elements from the toolbox of switches on the nanoscale, considering the critical factors of such systems for success in clinical application with regard to complement activation and hypersensitivity reactions in particular against polyethylene glycol (PEG). This chapter extends and updates an earlier review on this topic [11].

Figure 1.1 Schematic illustration, showing established therapeutic nano-carrier platforms (NPs) in (pre)clinical development.

1.2 Nanotechnology Carrier Platforms Suited for Switch Functionality

In recent years, major efforts have been devoted to develop suitable nanotechnological platforms to improve drug delivery to tumor tissue. For the development of such platforms, several challenges need to be mastered: (i) the control of the particle size, which can have influence on the NP distribution, clearance by kidney or liver and payload uptake; (ii) biocompatibility, to achieve an optimal benefit/risk relation; (iii) stealth properties, to escape immunological recognition and serum protein interactions; (iv) optimal blood circulation time for a specific application; (v) high target specificity for delivery of drugs or advanced functionality; (vi) controlled release mechanisms, e.g., endosomal escape; (vii) further functionality control through stimuli responsiveness. Multiple nanoscale platforms have been developed for this purpose, of which the most important will be discussed now.

1.2.1 Micelles and Liposomes

Lipid micelles are spherical nanosized structures characterized by a hydrophobic core and a hydrophilic coat (lipid bilayer) that may form spontaneously from amphiphilic molecules (phospholipids) in aqueous environments. They are suitable to encapsulate and transport hydrophobic molecules to (targeted) cells (e.g., hydrophobic drugs: taxanes [12, 13]). Liposomes can be prepared in various ways resulting in uni-laminar or multi-laminar liposomes. Uni-laminar liposomes range in size from approximately 50–250 nm have an aqueous core and are suitable for the loading of hydrophilic drugs, whereas multi-laminar liposomes usually have a diameter ranging 1–5 µm and are suitable for the loading of hydrophobic drugs due to the limited aqueous space [14, 15]. Under specific conditions, liposomes of 100 nm in diameter have been successfully used to deliver chemotherapeutic ∼ agents to tumors [16]. Drug delivery of poorly soluble molecules can be achieved through micelles using lipid moieties as hydrophobic blocks linked to hydrophilic polymers [17]. Different lipids have different fatty acid chain lengths and head groups which is resulting in a broad range of achievable physicochemical characteristics like minimal micellar concentration or melting temperature, allowing the creation of environment-sensitive (e.g., temperature-, pH-sensitive, mechano-sensitive) liposomes by choosing the specific setup. Several liposome-based cancer drugs have entered the clinical domain, e.g., carrying the anthracyclines doxorubicin (Doxil, Myocet, Caelyx) for the treatment of Kaposi’s sarcoma, treatment-refractory ovarian cancer, multiple myeloma, and metastatic breast cancer or daunorubicin (DaunoXome) for treatment of Kaposi’s sarcoma [18–21]. Beyond approved agents, liposomal chemotherapeutics are finding their way into clinical trials [22–24]. One important direction is the development of receptor-specific targeting for cell-specific delivery, which may render liposomes suited for purposes such as siRNA delivery, as reported by Zang et al. delivering siRNA by using pH-sensitive liposomes targeted to breast cancer using an anti-EphA10 antibody [25].

Liposomes are interesting carrier candidates for the delivery of intelligent switches at the nanoscale because the inner aqueous core offers a “nanocompartment” where processes may take place that require protection from the surrounding body fluids when injected into an ...

Table of contents

• Cover
• Half Title
• Series Page
• Title Page
• Copyright Page
• Contents
• Preface
• 1 Intelligent Nanomaterials for Medicine: Carrier Platforms and Targeting Strategies—State of the Art
• 2 Nanocarriers as an Emerging Platform for Cancer Therapy
• 3 Microfluidic Technologies for Accelerating the Clinical Translation of Nanoparticles
• 4 Theranostic Nanomedicine
• 5 The Emerging Field of RNA Nanotechnology
• 6 Drug Targeting to Tumors: Principles, Pitfalls and (Pre-) Clinical Progress
• 7 Biomolecular Coronas Provide the Biological Identity of Nanosized Materials
• 8 Protein–Nanoparticle Interactions
• 9 Rapid Formation of Plasma Protein Corona Critically Affects Nanoparticle Pathophysiology
• 10 Normalization of Tumour Blood Vessels Improves the Delivery of Nanomedicines in a Size-Dependent Manner
• 11 The Properties and Applications of Nanodiamonds
• 12 Nanotechnological Strategies for Engineering Complex Tissues
• 13 Promises, Facts and Challenges for Carbon Nanotubes in Imaging and Therapeutics
• 14 In vivo Biodistribution and Highly Efficient Tumour Targeting of Carbon Nanotubes in Mice
• 15 A Pilot Study in Non-Human Primates Shows No Adverse Response to Intravenous Injection of Quantum Dots
• 16 Nanomedicines for Ocular NSAIDs: State-of-the-Art Update of the Safety on Drug Delivery
• 17 Rare Earth Nanoparticles Prevent Retinal Degeneration Induced by Intracellular Peroxides
• 18 Nanomechanical Analysis of Cells from Cancer Patients
• 19 Multi-Electrode Array Technologies for Neuroscience and Cardiology
• Index