Changing Fate: Reprogramming Cells via Engineered Nanoscale Delivery Materials

Abstract

The incorporation of nanotechnology in regenerative medicine is at the nexus of fundamental innovations and early‐stage breakthroughs, enabling exciting biomedical advances. One of the most exciting recent developments is the use of nanoscale constructs to influence the fate of cells, which are the basic building blocks of healthy function. Appropriate cell types can be effectively manipulated by direct cell reprogramming; a robust technique to manipulate cellular function and fate, underpinning burgeoning advances in drug delivery systems, regenerative medicine, and disease remodeling. Individual transcription factors, or combinations thereof, can be introduced into cells using both viral and nonviral delivery systems. Existing approaches have inherent limitations. Viral‐based tools include issues of viral integration into the genome of the cells, the propensity for uncontrollable silencing, reduced copy potential and cell specificity, and neutralization via the immune response. Current nonviral cell reprogramming tools generally suffer from inferior expression efficiency. Nanomaterials are increasingly being explored to address these challenges and improve the efficacy of both viral and nonviral delivery because of their unique properties such as small size and high surface area. This review presents the state‐of‐the‐art research in cell reprogramming, focused on recent breakthroughs in the deployment of nanomaterials as cell reprogramming delivery tools.

Direct Reprogramming of Mouse Fibroblasts to Osteoblast-like Cells Using Runx2/Dlx5 Factors on Engineered Stiff Hydrogels

“…Moreover, nonviral methods have been developed as alternatives to induce the reprogramming process, 46 since the use of virus vectors poses safety challenges to clinical translation. It is encouraging to notice that, when the nonviral transfection was adopted in our case, the primary reprogramed cells and the subsequent cells after proliferation still demonstrated lasting osteogenic functions in vitro and in vivo, demonstrating the therapeutic potential of the reprogramming somatic cells into the osteogenic cells.…”

Simple Complexity: Incorporating Bioinspired Delivery Machinery within Self-Assembled Peptide Biogels

“…This presentation must ensure that the therapeutic payload is both protected from the biological environment that may degrade it, administered in a dose-dependent, safe manner [ 10 ] to minimize off-target effects, and be co-located to the site of therapeutic need [ 11 ]. Numerous strategies have been developed to achieve this, from simple injection [ 12 ], through to biologically stimulated release [ 13 ]. This typically entails loading drugs onto (nano)particles [ 14 ], encapsulating in vesicles [ 15 ], reversibly attaching to polymers [ 16 ], or using bulk hydrogels to immobilize the drug via steric hinderance [ 17 ].…”

“…Gene delivery is a targeted therapeutic strategy for renovation of diseased cells/tissues/organs or to impede disease progression [ 17 ]. Gene therapy has great potential to deal with the primary causes of incurable gene-related diseases, as well as help illustrate fundamental disease mechanisms in research [ 12 ]. During the processes of gene delivery, genes are introduced into host cells via vehicles.…”

Enhanced Intracellular Delivery and Cell Harvest Using a Candle Soot-Based Photothermal Platform with Dual-Stimulus Responsiveness

“…Intracellular delivery introduces exogenous cargoes, such as bioactive molecules and functional materials, into cells to regulate their behaviors and engineer their properties. , As most delivered “cargoes” are membrane-impermeable, different intracellular delivery strategies have been developed. − Among them, photothermal-induced membrane disruption delivery is attractive, which is based on photothermal thermal agents (PTAs) to convert light energy into heat to dissociate the phospholipid bilayer or generate smaller sized transient “holes” in the cell membrane of adjacent cells, providing a direct and rapid way to deliver cargo into cells. − Compared with other delivery methods, it has several advantageous features, such as ease of operation, simple equipment, and good control of delivery spatiotemporally. Photothermal surfaces with immobilized/embedded PTAs show high-efficiency delivery because of the enhanced interaction between cells and PTAs .…”