Biomaterials for in situ cell therapy

Abstract

Cell therapy has revolutionized the treatment of various diseases, such as cancers, genetic disorders, and autoimmune diseases. Currently, most cell therapy products rely on ex vivo cell engineering, which requires sophisticated manufacturing processes and poses safety concerns. The implementation of in situ cell therapy holds the potential to overcome the current limitations of cell therapy and provides a broad range of applications and clinical feasibility in the future. A variety of biomaterials have been developed to improve the function and target delivery to specific cell types due to their excellent biocompatibility, tunable properties, and other functionalities, which provide a reliable method to achieve in vivo modulation of cell reprogramming. In this article, we summarize recent advances in biomaterials for in situ cell therapy including T cells, macrophages, dendritic cells, and stem cells reprogramming leveraging lipid nanoparticles, polymers, inorganic materials, and other biomaterials. Finally, we discuss the current challenges and future perspectives of biomaterials for in situ cell therapy.

Keywords: biomaterial; cell therapy; drug delivery; in situ.

FIGURE 1

Schematic diagram illustrating the reprogramming of T cells, macrophages, dendritic cells, and stem cells in situ using agents carried by biomaterials. Biomaterials with certain physicochemical properties allow them to target specific cells. Also, they can be modified with diverse ligands for improved cell specificity. Upon the administration of the biomaterials into the patient, their targeting ability facilitates binding to the specific cells, resulting in the subsequent release of encapsulated cargo such as small molecules, nucleic acids, or other components. This release induces in situ cell reprogramming, leading to the formation of multifunctional cells, and ultimately enabling effective in vivo therapy.

FIGURE 2

(a) Construction of the T-cell-targeted DNA-carrying polymer nanoparticles. (b) Reprogramming of T cells in situ to express tumor-specific CARs using DNA-carrying polymer nanoparticles. (Reproduced with permission from ref , .^[15,45] Copyright © 2021 by Annual Reviews. Distributed under a Creative Commons Attribution License 4.0 (CC BY) https://creativecommons.org/licenses/by/4.0/).

FIGURE 3

(a) Illustration of the CD133-specific CAR-Ms by hydrogel-nanoporter, (b) M2-like macrophages and (c) M1-like macrophages in tumor sites, (d) Survival rate of mice after treatments (Reproduced with permission from ref .^[75] Copyright © 2022, The American Association for the Advancement of Science).

FIGURE 4

(a) Preparation of all-in-one nanomedicine, (b) Illustration of restoring specific immune tolerance (Reproduced with permission from ref .^[102] Copyright 2020 American Chemical Society).

FIGURE 5

(a) Synthesis of lipid-polymer hybrid materials and nanoparticle formulation by microfluidic mixing, (b) After injecting NicheEC-15 with AF647-siRNA, colocalization was observed in the skull bone marrow within 2 h, (c) Masson’s trichrome staining of the left ventricle after NicheEC-15-siMcp1 treatment (Reproduced with permission from ref .^[130] Copyright 2020 Spinger-Nature).