Polymeric Nanoparticles Amenable to Simultaneous Installation of Exterior Targeting and Interior Therapeutic Proteins

Abstract

Effective delivery of therapeutic proteins a formidable challenge. Herein, using a unique polymer family with a wide-ranging set of cationic and hydrophobic features, we developed a novel nanoparticle (NP) platform capable of installing protein ligands on the particle surface and simultaneously carrying therapeutic proteins inside by a self-assembly procedure. The loaded therapeutic proteins (e.g., insulin) within the NPs exhibited sustained and tunable release, while the surface-coated protein ligands (e.g., transferrin) were demonstrated to alter the NP cellular behaviors. In vivo results revealed that the transferrin-coated NPs can effectively be transported across the intestinal epithelium for oral insulin delivery, leading to a notable hypoglycemic response.

Cancer nanomedicine: progress, challenges and opportunities

“…2f). Moreover, active targeting is of importance when tissue accumulation does not depend on EPR (for example, vascular targeting) 148 or when the delivery of therapeutic agents requires active transcytosis of physiological barriers such as the intestinal mucosa or the blood–brain barrier 149–151 . Since the concept of active NP targeting was introduced more than 30 years ago 152,153 , a few examples have made their way into clinical trials 9 , including targeted liposomes (for example, HER2 (also known as ERBB2) single-chain variable fragment (scFv)-targeted liposome (MM-302) 154 ), the first targeted and controlled-release polymeric NP (BIND-014) 11 and the first targeted siRNA NP (CALAA-01) 30 .…”

Cellular uptake of nanoparticles: journey inside the cell

“…The microenvironment of the gastrointestinal (GI) tract, including extreme pH, enzymatic degradation, and poor permeability of the intestinal epithelium are critical in determining the NPs to be degraded or to cross the intestinal epithelium via transcytosis. 27 Therefore, when we design NPs for different applications, the microenvironment of the target cells should be carefully considered, since it greatly influences the performance of NPs, determining where they go and what kind of cells they interact with. 6, 24 …”

Polymeric nanoparticles for colon cancer therapy: overview and perspectives

“…7 To overcome these obstacles, polymers, dendrimers, lipids as well as organometallic and carbon-based materials have been used as carrier systems in colorectal cancer therapy. [8][9][10][11] Recent evidence suggests that the advent of nanotechnology marks an unparalleled opportunity to advance the treatment of CRC. 12,13 Although a small number of nanosized drug delivery carriers have been approved for human use, nanotechnologies will likely constitute a growing share of the oncologist's therapeutic arsenal for decades to come.…”