Halloysite nanotubes (HNTs) are hollow clay nanotubes in the nanometer size range, made up of double-layered aluminum silicate mineral layers. HNTs represent an extremely versatile, safe, and biocompatible nanomaterial, used in a wide range of applications in biomedicine and nanomedicine. For example, they are used as transporters for the controlled release of drugs or genes, in tissue engineering, in the isolation of stem cells and cancer cells, and in bioimaging. Consequently, the assessment of the biocompatibility of HNTs has acquired considerable importance. In recent years, HNT composites have attracted attention due to their improved biocompatibility, compared to HNTs, suggesting potential for applications in tissue engineering or as vehicles for drugs or genes. In this review, recent advances in the application of HNTs and HNT composites in biomedicine are discussed to provide a valuable guide to scientists in the design and development of viable, functional bio-devices for biomedical applications.

This study aimed to investigate the ability of disulphide-less crotamine (dLCr) to complex DNA and to evaluate whether the DNA–dLCr complex is capable of improving transfection in bovine embryos. Three experiments were performed to: (i) evaluate the formation and stability of the DNA–dLCr complex; (ii) assess the dLCr embryotoxicity by exposure of bovine embryos to dLCr; and (iii) assess the efficiency of bovine embryo transfection after microinjection of the DNA–dLCr complex or green fluorescent protein (GFP) plasmid alone (control). DNA complexation by dLCr after 30 min of incubation at 1:100 and 1:50 proportions presented higher efficiency (P < 0.05) than the two controls: native crotamine (NCr) 1:10 and lipofectamine. There was no difference between DNA–dLCr 1:25 and the controls. The DNA–dLCr complexation was evaluated at different proportions and times. In all, at least half of maximum complexation was achieved within the initial 30 min. No embryotoxicity of dLCr was verified after exposure of in vitro fertilized embryos to different concentrations of the peptide. The effectiveness of dLCr to improve exogenous gene expression was evaluated by microinjection of the DNA–dLCr complex into in vitro fertilized zygotes, followed by verification of both embryo development and GFP expression. From embryos microinjected with DNA only, 4.6% and 2.8% expressed the GFP transgene at day 5 and day 7, respectively. The DNA–dLCr complex did not increase the number of GFP-positive embryos. In conclusion, dLCr forms a complex with DNA and its application in in vitro culture is possible. However, the dLCr peptide sequence should be redesigned to improve GFP expression.

In recent years, stimuli responsive polymer based gene delivery vehicle design for cancer treatment and treatment of other genetic disorders has received extensive attention. Early studies focusing on DNA delivery have been facilitated by functional polymers and this area has seen further growth spurred by recent gene silencing strategies developed for small RNA [i.e., small interfering RNA (siRNA) or micro RNA (miRNA)] delivery. DNA and small RNAs possess analogous properties; however, their explicit differences define the specific challenges associated with the delivery route and the design of functional materials to overcome distinct challenges. Apart from classical gene delivery, the recent advances in genome editing have revealed the necessity of new delivery devices for genome editing tools. A system involving CRISPR (clustered, regularly interspaced, short palindromic repeats) and an endonuclease CRISPR-associated protein 9 (Cas9) coupled with a short, single-guide RNA (sgRNA) has emerged as a promising tool for genome editing along with functional delivery systems. For all these nucleic acid based treatments, the internal or external physiochemical changes in the biological tissue/cells play a major role in the design of stimuli responsive delivery materials for both in vitro and in vivo applications. This review emphasizes the recent advances in the use of pH, temperature, and redox potential-responsive polymers overcoming hurdles for delivery of gene and gene editing tools for both in vitro and in vivo applications. Specifically the chapter focuses on recently proposed delivery strategies, types of delivery systems, and polymer synthesis/modification methods. The recent advances in CRISPR/Cas9-sgRNA technology and delivery are also described in a separate section. The review ends with current clinical trials, concluding remarks, and future perspectives.

Nonviral DNA delivery systems have great therapeutic and prophylactic potential, but their clinical utility has been limited by three major barriers: (1) inefficient uptake by the cell, (2) insufficient release of DNA within the cell, and (3) ineffective nuclear targeting and transport. Since the size of most cells is in the micrometer regime and the space inside a cell is extremely crowded, ideal DNA delivery systems must be in the nanometer range. Advancements in nanoscale science and nanotechnology have provided us with novel nanoparticles that may overcome all of these barriers, leading to higher-efficiency DNA delivery. This review article will focus on the recent developments in nanoscale DNA delivery systems that consist of chemical dendrimers, DNA dendrimers, nanospheres, nanolayers, nanorods, and nanotubes. The future of DNA delivery systems that interface with nanotechnology is also discussed.

The Human Genome Project continues to reveal the genetic basis for numerous acquired and inherited diseases ranging from cancer, HIV, and heart disease to muscular dystrophy and hemophilia. With this wealth of information, the ability to design patient-specific drugs that alter the cellular machinery at the genetic level in a way that controls or treats a specific disease will increasingly become a reality. Designing nucleic acid drugs as well as engineering novel delivery vehicles that encapsulate and effectively transport genetic materials into cells provides an opportunity to enhance the understanding of disease mechanisms and may help treat or cure these diseases. This issue of MRS Bulletin on “Designer Materials for Nucleic Acid Delivery” explores the diverse materials—polymers, lipids, nanoparticles, biocompatible scaffolds, and engineered peptides—that are being evaluated for the intracellular delivery of nucleic acids. These synthetic delivery systems are actively being investigated for many research purposes that range from gene-based therapy, genetic vaccine, and RNA interference to gene function and cellular signaling studies. This area is currently being pursued by a broad group of academic, clinical, and industrial researchers at both the fundamental and applied level, motivated by the widespread implications for human health. In this introductory article, we provide a general tutorial to gene-based therapies and a brief overview of the many areas of materials research that are currently making a tremendous impact on this interdisciplinary field.We conclude with a discussion of the future challenges that materials researchers face in developing viable nucleic acid delivery vehicles.

Gene therapy harbors great promise for the treatment of a variety of inherited and acquired diseases, but its potential can be realized only with safe and effective carriers. Although viruses can efficiently transfer foreign genes to cells, their long-term safety remains a concern. Polymers can serve as a carrier to facilitate gene transfer, either by condensing DNA to the size of nanoparticles that can be internalized by cells, or by entrapping DNA in matrices or micro/nanoparticles for sustained release. However, polymeric controlled gene delivery remains highly inefficient. This review covers the major barriers for nonviral gene transfer and briefly describes the different types of polymers developed to overcome these barriers. With the tremendous promise of genetic medicine, nonviral gene delivery is a worthy goal for biomaterials and nanotechnology research.

Delivery systems for tumour targeting fall into two basic categories: drug conjugate systems, in which individual drug molecules are chemically modified to target them directly to the tumour; and carrier-based systems, in which the drug or gene is first packaged non-covalently into a synthetic carrier that is then targeted to the tumour. In both cases, the objective is to maximise exposure of the target cells to the drug yet minimise side effects that result from nonspecific toxicity in normal tissues. The creation of such dose differentials is based on phenotypic differences between the tumour and the rest of the body. However, although a wide range of such changes have been linked to the transformation of normal cells to cancer cells, no single common feature exists to allow unambiguous targeting to the tumour. In addition, the tumour microenvironment creates physical barriers that significantly impair transport within the tumour. It is therefore important to match the delivery requirements of the drug to the capabilities of the delivery system. In this review, a brief overview is given of the underlying concepts and principles that help guide the development of such tumour-targeting strategies.