Recent advances in the development of genome editing technologies based on programmable nucleases have substantially improved our ability to make precise changes in the genomes of eukaryotic cells. Genome editing is already broadening our ability to elucidate the contribution of genetics to disease by facilitating the creation of more accurate cellular and animal models of pathological processes. A particularly tantalizing application of programmable nucleases is the potential to directly correct genetic mutations in affected tissues and cells to treat diseases that are refractory to traditional therapies. Here we discuss current progress toward developing programmable nuclease–based therapies as well as future prospects and challenges.

Therapeutic genome editing: prospects and challenges

Recent progress in drug delivery

Phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) employs phototherapeutic agents to generate heat or cytotoxic reactive oxygen species (ROS), and has therefore garnered particular interest for cancer therapy. However, the main challenges faced by conventional phototherapeutic agents include easy recognition by the immune system, rapid clearance from blood circulation, and low accumulation in target sites. Cell-membrane coating has emerged as a potential way to overcome these limitations, owing to the abundant proteins on the surface of cell membranes that can be inherited to the cell membrane-camouflaged nanoparticles. This review summarizes the recent advances in the development of biomimetic cell membrane-camouflaged nanoparticles for cancer phototherapy. Different sources of cell membranes can be used to coat nanoparticles uisng different coating approaches. After cell-membrane coating, the photophysical properties of the original phototherapeutic nanoparticles remain nearly unchanged; however, the coated nanoparticles are equipped with additional physiological features including immune escape, in vivo prolonged circulation time, or homologous targeting, depending on the cell sources. Moreover, the coated cell membrane can be ablated from phototherapeutic nanoparticles under laser irradiation, leading to drug release and thus synergetic therapy. By combining other supplementary agents to normalize tumor microenvironment, cell-membrane coating can further enhance the therapeutic efficacy against cancer.

Recent Advances in Cell Membrane-Camouflaged Nanoparticles for Cancer Phototherapy.

Nuclear delivery and accumulation are very important for many anticancer drugs that interact with DNA or its associated enzymes in the nucleus. However, it is very difficult for neutrally and negatively charged anticancer drugs such as 10-hydroxycamptothecine (HCPT). Here we report a simple strategy to construct supramolecular nanomedicines for nuclear delivery of dual synergistic anticancer drugs. Our strategy utilizes the coassembly of a negatively charged HCPT-peptide amphiphile and the positively charged cisplatin. The resulting nanomaterials behave as the “Trojan Horse” that transported soldiers (anticancer drugs) across the walls of the castle (cell and nucleus membranes). Therefore, they show improved inhibition capacity to cancer cells including the drug resistant cancer cell and promote the synergistic tumor suppression property in vivo. We envision that our strategy of constructing nanomaterials by metal chelation would offer new opportunities to develop nanomedicines for combination chemotherapy.

Supramolecular “Trojan Horse” for Nuclear Delivery of Dual Anticancer Drugs

Recently, diverse functional materials that take subcellular structures as therapeutic targets are playing increasingly important roles in cancer therapy Here, particular emphasis is placed on four kinds of therapies, including chemotherapy, gene therapy, photodynamic therapy (PDT), and hyperthermal therapy, which are the most widely used approaches for killing cancer cells by the specific destruction of subcellular organelles Moreover, some non-drug-loaded nanoformulations (ie, metal nanoparticles and molecular self-assemblies) with a fatal effect on cells by influencing the subcellular functions without the use of any drug molecules are also included According to the basic principles and unique performances of each treatment, appropriate strategies are developed to meet task-specific applications by integrating specific materials, ligands, as well as methods In addition, the combination of two or more therapies based on multifunctional nanostructures, which either directly target specific subcellular organelles or release organelle-targeted therapeutics, is also introduced with the intent of superadditive therapeutic effects Finally, the related challenges of critical re-evaluation of this emerging field are presented

Recent Advances in Subcellular Targeted Cancer Therapy Based on Functional Materials.

https://escholarship.org/content/qt55t519c0/qt55t519c0.pdf?t=o3dosu

"Combo" nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Molecular genetics and emerging therapies for retinitis pigmentosa: Basic research and clinical perspectives

Modern medicine has been waging a war on cancer for nearly a century with no tangible end in sight. Cancer treatments have significantly progressed, but the need to increase specificity and decrease systemic toxicities remains. Early diagnosis holds a key to improving prognostic outlook and patient quality of life, and diagnostic tools are on the cusp of a technological revolution. Nanotechnology has steadily expanded into the reaches of cancer chemotherapy, radiotherapy, diagnostics, and imaging, demonstrating the capacity to augment each and advance patient care. Nanomaterials provide an abundance of versatility, functionality, and applications to engineer specifically targeted cancer medicine, accurate early-detection devices, robust imaging modalities, and enhanced radiotherapy adjuvants. This review provides insights into the current clinical and pre-clinical nanotechnological applications for cancer drug therapy, diagnostics, imaging, and radiation therapy.

Jessica A. Kemp

Papers

"Combo" nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Molecular genetics and emerging therapies for retinitis pigmentosa: Basic research and clinical perspectives

Cancer nanotechnology: current status and perspectives.

Biocompatible Chemotherapy for Leukemia by Acid-Cleavable, PEGylated FTY720.

Nano-antibiotics: Nanotechnology in Fighting Against Infectious Diseases