Structure–function relationships in polymeric multilayer capsules designed for cancer drug delivery

Abstract

Targeted delivery of cancer drugs to tumor-specific molecular targets represents a major challenge in modern personalized cancer medicine. Engineering of micron and submicron polymeric multilayer capsules allows obtaining multifunctional theranostic...

A decade of developing applications exploiting the properties of polyelectrolyte multilayer capsules

“…307 Microcapsule-based drug delivery systems have attracted broad interests for cancer treatment in recent years due to their distinct characteristics, including the capability of enhancing permeability and retention (EPR) effect with reduced size and the possibility to refine the surface for precisely recognizing the attributes of the healthy cells and cancer cells in the clinical contexts. 308,309 Co-delivery of dual drugs, doxorubicin (DOX) and mitoxantrone (MTX), has been developed based on liposomal nanoparticle capsules which significantly reduce the clearance rate of the two drugs and prolong their circulation time in vivo. 310 Microcapsules not only provide cells containment at implantation site but also protect them from adverse environment such as host immunoresponse, degradation and shear stress.…”

Impact of Macrophages on the Interaction of Cetuximab-Functionalized Polyelectrolyte Capsules with EGFR-Expressing Cancer Cells

“…Effective uptake and internalization of spherical particles from 30 nm to 3–5 μm in size by cancer cells and tumor-derived macrophages were observed. , Large (5.1 ± 1.4 μm) hybrid QD-encoded functionalized PCs were earlier demonstrated to effectively interact with both cancer cells and macrophages. , However, reducing the size and increasing the homogeneity of the PCs enhance their internalization , and the efficiency of targeted delivery.…”

“…This approach yielded a highly dense layer of cetuximab molecules conjugated to the PC surface, their number (∼10 6 ) being comparable to the number of EGFR molecules expressed by a cancer cell (≥10 6 ) . In this case, randomly oriented immobilization ensured that the active sites of at least 50% of the bound Ab molecules (Figure S4, Supporting Information) be accessible for selective interaction with the molecular targets . The Ab molecules oriented otherwise can serve as a “spatial filler” between the Ab molecules whose active sites face outward, which facilitates the binding to the target cells by decreasing the steric hindrance effect …”

“…The morphology and rigidity of the PC surface have also been shown to affect their interaction with the target cancer cells . Therefore, the PCs were analyzed by means of AFM for a detailed characterization of their surface morphology.…”

“…The unmodified PCs had a rough, granular surface due to the domain/globular structure of the assembled polyelectrolyte layers (Figure B, upper panel). Quenching and additional treatment of the surface with an inert protein (BSA), also known as surface back-coating, were found to minimize the roughness of the PCs surface (Figure B, bottom panel), blocking the surface and probably reducing nonspecific interaction of the PCs with cells …”