Nano-Sized Albumin-Copolymer Micelles for Efficient Doxorubicin Delivery

Abstract

We present the discovery of a nano-sized protein-derived micellar drug delivery system based on the polycationic albumin precursor protein cBSA-147. The anticancer drug doxorubicin (DOX) was efficiently encapsulated into nanosized micelles based on hydrophobic interactions with the polypeptide scaffold. These micelles revealed attractive stabilities in various physiological buffers and a wide pH range as well as very efficient uptake into A549 cells after 1 h incubation time only. In vitro cytotoxicity was five-times increased compared to free DOX also indicating efficient intracellular drug release. In addition, multiple functional groups are available for further chemical modifications. Based on the hydrophobic loading mechanism, various classical anti-cancer drugs, in principle, could be delivered even synergistically in a single micelle. Considering these aspects, this denatured albumin-based drug delivery system represents a highly attractive platform for nanomedicine approaches towards cancer therapy.

Organ-on-a-chip platforms for studying drug delivery systems

“…Aerosol nanocomplexes for gene therapy have proven to diffuse through the alveoli-capillary barrier in an efficient manner compared to other particles due to their small size [105]. Other drug delivery systems like zinc oxide nanoparticles (ZnONP) [106], silver nanoparticles (AgNP) [107] and doxorubicin micelles [108] have been used with 2D culture platforms to study the effect on cell function and apoptotic response. Multi-well plate cultures of MCF-7 and A549 lung cancer cell lines have been used to evaluate nanoparticles [109].…”

Drug Delivery Vehicles Based on Albumin–Polymer Conjugates

“…Polymer nanoparticles with albumin building blocks prepared by a) surface modification of albumin nanoparticle with polymers; b) self‐assembly of albumin–polymer conjugates c) unfolding of albumin and subsequent functionalization. [36a],…”

Precision Biopolymers from Protein Precursors for Biomedical Applications

“…HSA‐ and BSA‐derived PcPs, in particular those functionalized with additional lipophilic groups such as ethynyl or thiotic acid groups, can accommodate lipophilic guest molecules 33, 38. The incorporation of these additional lipophilic groups most likely leads to a collapse of the polypeptide architecture indicated by a decrease in R H and the formation of very small micelles with similar diameters as proteins (Figure 6, Figure 7b) 33.…”

“…dcBSA‐PEO(5000) 27 ‐alkyne has been investigated as a carrier for hydrophobic drugs due to the formation of lipophilic cavities that allow the encapsulation of hydrophobic drug molecules as well as the presence of multiple positive charges to facilitate cell uptake by endocytosis 38. Doxorubicin (DOX), a hydrophobic anticancer drug, has been encapsulated into dcBSA‐PEO(5000) 27 ‐alkyne with a high loading of 14 DOX per carrier to form very stable, nanoscopic micelles of around 30 nm dimensions with narrow size distributions (Figure 8).…”

“…Doxorubicin (DOX), a hydrophobic anticancer drug, has been encapsulated into dcBSA‐PEO(5000) 27 ‐alkyne with a high loading of 14 DOX per carrier to form very stable, nanoscopic micelles of around 30 nm dimensions with narrow size distributions (Figure 8). 38 The PcP‐drug assembly exhibits a fivefold increased cell uptake and significant cytotoxicity toward HeLa cell lines compared with the free drug. This PcP nanocarrier addresses some limitations of existing albumin‐based drug delivery systems such as their drug loading capacity as well as noticeable drug leakage 53…”