Lipid-, Inorganic-, Polymer-, and DNA-Based Nanocarriers for Delivery of the CRISPR/Cas9 system.

The clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (CRISPR/Cas9) system has been widely explored for the precise manipulation of target DNA and has enabled efficient genomic editing in cells. Recently, CRISPR/Cas9 has shown promising potential in biomedical applications, including disease treatment, transcriptional regulation and genome-wide screening. Despite these exciting achievements, efficient and controlled delivery of the CRISPR/Cas9 system has remained a critical obstacle to its further application. Herein, we elaborate on the three delivery forms of the CRISPR/Cas9 system, and discuss the composition, advantages and limitations of these forms. Then we provide a comprehensive overview of the carriers of the system, and focus on the nonviral nanocarriers in chemical methods that facilitate efficient and controlled delivery of the CRISPR/Cas9 system. Finally, we discuss the challenges and prospects of the delivery methods of the CRISPR/Cas9 system in depth, and propose strategies to address the intracellular and extracellular barriers to delivery in clinical applications.

Inorganic Nano-Targeted Drugs Delivery System and Its Application of Platinum-Based Anticancer Drugs.

As one of the most important anticancer drugs, cisplatin and its analogues have been widely used in chemotherapy regimens of various tumors. However, a series of side effects and resistance/cross-resistance have been becoming the main obstacles which limit their application and effectiveness. Recent researches suggest that inorganic nano-materials which act as targeted drug delivery carriers of platinum-based anticancer drugs not only enhance the antitumor activity of platinum-based drugs, but also reduce the side effects and resistance. The nano-targeted drugs delivery system provides a new strategy in clinical application of platinum-based anticancer drugs. This review will focus on recent advances in inorganic nano-carriers for platinum-based targeted drugs delivery system.

Nanostructures as Radionuclide Carriers in Auger Electron Therapy.

The concept of nanoparticle-mediated radionuclide delivery in the cancer treatment has been widely discussed in the past decade. In particular, the use of inorganic and organic nanostructures in the development of radiopharmaceuticals enables the delivery of medically important radioisotopes for radionuclide therapy. In this review, we present the development of nanostructures for cancer therapy with Auger electron radionuclides. Following that, different types of nanoconstructs that can be used as carriers for Auger electron emitters, design principles, nanoparticle materials, and target vectors that overcame the main difficulties are described. In addition, systems in which high-Z element nanoparticles are used as radionuclide carriers, causing the emission of photoelectrons from the nanoparticle surface, are presented. Finally, future research opportunities in the field are discussed as well as issues that must be addressed before nanoparticle-based Auger electron radionuclide therapy can be transferred to clinical use.

Nanocarriers in effective pulmonary delivery of siRNA: current approaches and challenges.

Research on siRNA is increasing due to its wide applicability as a therapeutic agent in irreversible medical conditions. siRNA inhibits expression of the specific gene after its delivery from formulation to cytosol region of a cell. RNAi (RNA interference) is a mechanism by which siRNA is silencing gene expression for a particular disease. Numerous studies revealed that naked siRNA delivery is not preferred due to instability and poor pharmacokinetic performance. Nanocarriers based delivery of siRNA has the advantage to overcome physiological barriers and protect the integrity of siRNA from degradation by RNAase. Various diseases like lung cancer, cystic fibrosis, asthma, etc can be treated effectively by local lung delivery. The selective targeted therapeutic action in diseased organ and least off targeted cytotoxicity are the key benefits of pulmonary delivery. The current review highlights recent developments in pulmonary delivery of siRNA with novel nanosized formulation approach with the proven in vitro/in vivo applications.

Neuronanomedicine: An Up-to-Date Overview.

The field of neuronanomedicine has recently emerged as the bridge between neurological sciences and nanotechnology. The possibilities of this novel perspective are promising for the diagnosis and treatment strategies of severe central nervous system disorders. Therefore, the development of nano-vehicles capable of permeating the blood⁻brain barrier (BBB) and reaching the brain parenchyma may lead to breakthrough therapies that could improve life expectancy and quality of the patients diagnosed with brain disorders. The aim of this review is to summarize the recently developed organic, inorganic, and biological nanocarriers that could be used for the delivery of imaging and therapeutic agents to the brain, as well as the latest studies on the use of nanomaterials in brain cancer, neurodegenerative diseases, and stroke. Additionally, the main challenges and limitations associated with the use of these nanocarriers are briefly presented.

Overview on Inhalable Nanocarriers for Respiratory Immunization.

Despite the value of vaccination, the control of re-emerging infectious and non-infectious diseases remains a challenge for researchers. In this topic, mucosal immunization, in particular at airway mucosa, is receiving increased investigational focus. Innovative vaccine platforms to deliver immunogens with or without adjuvants in a safe and stable manner have been explored to improve vaccine efficacy and induce long-term and protective immunity. This review provides an overview of the features of respiratory immunization and the fate of inhalable nanocarriers in the respiratory tract. The review also highlights the most representative delivery approaches based on inhalable nanocarriers, including polymeric, lipid and inorganic-based nanosystems, which can enhance vaccine uptake by antigen-presenting cells. The review takes into consideration the most relevant and recent in vivo studies to provide readers a realistic insight into the potential of these technologies in the advantages and potential hurdles to clinical and commercial success of these platforms for vaccination.