Practical methods to deliver proteins systemically in animals have been hampered by poor tissue penetration and inefficient cytoplasmic localization of internalized proteins. We therefore pursued the development of improved macromolecule transduction domains (MTDs) and tested their ability to deliver therapeutically active p18(INK4c). MTD103 was identified from a screen of 1,500 signal peptides; tested for the ability to promote protein uptake by cells and tissues; and analyzed with regard to the mechanism of protein uptake and the delivery of biologically active p18(INK4c) into cancer cells. The therapeutic potential of cell-permeable MTD103p18(INK4c) (CP-p18(INK4c)) was tested in the HCT116 tumor xenograft model. MTD103p18(INK4c) appeared to traverse plasma membranes directly, was transferred from cell-to-cell and was therapeutically effective against cancer xenografts, inhibiting tumor growth by 86-98% after 5 weeks (P < 0.05). The therapeutic responses to CP-p18(INK4c) were accompanied by high levels of apoptosis in tumor cells. In addition to enhancing systemic delivery of CP-p18(INK4c) to normal tissues and cancer xenografts, the MTD103 sequence delayed protein clearance from the blood, liver and spleen. These results demonstrate that macromolecule intracellular transduction technology (MITT), enabled by MTDs, may provide novel protein therapies against cancer and other diseases.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412482 | PMC |
| http://dx.doi.org/10.1038/mt.2012.102 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Optical sectioning methods in three-dimensional bioimaging.
Light Sci Appl
January 2025
Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China.
In recent advancements in life sciences, optical microscopy has played a crucial role in acquiring high-quality three-dimensional structural and functional information. However, the quality of 3D images is often compromised due to the intense scattering effect in biological tissues, compounded by several issues such as limited spatiotemporal resolution, low signal-to-noise ratio, inadequate depth of penetration, and high phototoxicity. Although various optical sectioning techniques have been developed to address these challenges, each method adheres to distinct imaging principles for specific applications.
View Article and Find Full Text PDFMapping axillary sensory cutaneous nerves for enhanced analgesic approaches in axillary surgery: a cadaveric study.
Reg Anesth Pain Med
December 2024
Department of Anesthesia and Perioperative Medicine, University of Western Ontario, London, Ontario, Canada
Background: Innervation of the breast includes branches of thoracic intercostal nerves, the superficial cervical plexus, the brachial plexus, and the intercostobrachial nerve (ICBN). Commonly used blocks for breast surgery provide incomplete analgesia of the axillary region. This cadaveric study aims to identify and map the axillary sensory cutaneous nerves.
View Article and Find Full Text PDFSurface enzyme-polymerization endows Janus hydrogel tough adhesion and regenerative repair in penetrating orocutaneous fistulas.
Nat Commun
December 2024
Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Penetrating orocutaneous or oropharyngeal fistulas (POFs), severe complications following unsuccessful oral or oropharyngeal reconstruction, remain complex clinical challenges due to lack of supportive tissue, contamination with saliva and chewed food, and dynamic oral environment. Here, we present a Janus hydrogel adhesive (JHA) with asymmetric functions on opposite sides fabricated via a facile surface enzyme-initiated polymerization (SEIP) approach, which self-entraps surface water and blood within an in-situ formed hydrogel layer (RL) to effectively bridge biological tissues with a supporting hydrogel (SL), achieving superior wet-adhesion and seamless wound plugging. The tough SL hydrogel interlocked with RL dissipates energy to withstand external mechanical stimuli from continuous oral motions like chewing and swallowing, thus reducing stress-induced damage.
View Article and Find Full Text PDFINSIHGT: an accessible multi-scale, multi-modal 3D spatial biology platform.
Nat Commun
December 2024
Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Biological systems are complex, encompassing intertwined spatial, molecular and functional features. However, methodological constraints limit the completeness of information that can be extracted. Here, we report the development of INSIHGT, a non-destructive, accessible three-dimensional (3D) spatial biology method utilizing superchaotropes and host-guest chemistry to achieve homogeneous, deep penetration of macromolecular probes up to centimeter scales, providing reliable semi-quantitative signals throughout the tissue volume.
View Article and Find Full Text PDFDescription of tissue profiles, thalamic location, and recommended penetrating captive bolt placement in cadaver heads from domesticated 24- to 48-mo-old male yaks ().
Transl Anim Sci
December 2024
Department of Animal and Food Science, University of Wisconsin - River Falls, River Falls, WI 54022, USA.
Yaks are a domesticated species utilized for meat, fiber, and transportation in many countries. In the United States, yak meat is growing in popularity due to its classification as a "healthy" meat. Penetrating captive bolt (PCB) is an approved method of preslaughter stunning and euthanasia for cattle.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!