Cell-penetrating peptides meditated encapsulation of protein therapeutics into intact red blood cells and its application

Abstract

Red blood cells (RBCs) based drug carrier appears to be the most appealing for protein drugs due to their unmatched biocompatability, biodegradability, and long lifespan in the circulation. Numerous methods for encapsulating protein drugs into RBCs were developed, however, most of them induce partial disruption of the cell membrane, resulting in irreversible alterations in both physical and chemical properties of RBCs. Herein, we introduce a novel method for encapsulating proteins into intact RBCs, which was meditated by a cell penetrating peptide (CPP) developed in our lab—low molecular weight protamine (LMWP). L-asparaginase, one of the primary drugs used in treatment of acute lymphoblastic leukemia (ALL), was chosen as a model protein to illustrate the encapsulation into erythrocytes mediated by CPPs. In addition current treatment of ALL using different L-asparaginase delivery and encapsulation methods as well as their associated problems were also reviewed.

Exploiting macrophages as targeted carrier to guide nanoparticles into glioma

“…In recent decades, cell based drug delivery systems take advantage of circulatory cell (red blood cell, T cell, macrophage, antigen presenting cell, etc.) to improve the therapeutic effect of anti-cancer drugs [15, 26, 27]. Using cells as carriers for drug delivery offers several advantages over free drug, including improved drug efficacy, extended half-lives, sustained drug release, and limited immunogenicity and cytotoxicity.…”

PTD-Modified ATTEMPTS for Enhanced Toxin-based Cancer Therapy: An In Vivo Proof-of-Concept Study

“…The fluorescence intensities of the organs were measured immediately by using the IVIS® spectrum imaging system (Xenogen, Alameda, CA). Ex/Em wavelength of 745 nm/800 nm, binning (8), exposure time (2 s), f/ stop (1) and fields of view (25 cm × 25 cm) were used identically for imaging all the organs. The fluorescence images were analyzed using Living Image 2.5 software (Xenogen, Alameda, CA) and mean fluorescence intensities (M.F.I.s) of the organs were calculated by subtracting the mean fluorescence intensity of the corresponding tissue from a blank mouse.…”

“…Due to the ability to deliver attached cargos (e.g. proteins, peptides and genes) into almost any type of cells (including brain and red blood cells) with an efficiency unmatched by other ligands (6-8), PTDs shed light to finally overcoming the cell membrane barrier, a major hindrance for many macromolecular drugs to exert their therapeutic efficacy (9-15). However, despite achieving certain successes in various research fields, clinical applications of PTDs has yet so far not been fully accomplished.…”

Next generation drug delivery: circulatory cells-mediated nanotherapeutic approaches

“…Moreover, combining the cell-mediated delivery with a stimuli-responsive mechanism is a promising area to explore and may have a significant impact on next-generation delivery applications to ensure safe and beneficial therapeutic effects [4]. Very few studies have used this concept in cell-based delivery; for example, intracellular glutathione level is applied as a stimulus for L-asparaginase release in RBCs [15]. Thus, the development of smart biomaterials are important in fabrication of effective cell-based delivery systems.…”