Bioengineering of Extracellular Vesicles: Exosome-Based Next-Generation Therapeutic Strategy in Cancer

Abstract

Extracellular nano vesicles and exosomes hold compelling evidence in intercellular communication. Exosomal intracellular signal transduction is mediated by the transfer of cargo proteins, lipids, micro (mi)RNAs, long noncoding (lnc)RNAs, small interfering (si)RNAs, DNA, and other functional molecules that play a pivotal role in regulating tumor growth and metastasis. However, emerging research trends indicate that exosomes may be used as a promising tool in anticancer treatment. This review features a majority of the bioengineering applications of fabricated exosomal cargoes. It also encompasses how the manipulation and delivery of specific cargoes—noncoding RNAs (ncRNAs), recombinant proteins, immune-modulators, chemotherapeutic drugs, and other small molecules—may serve as a precise therapeutic approach in cancer management.

Mesenchymal Stem Cell-Derived Exosomal microRNAs in Cardiac Regeneration

“…MSCs can be manipulated for intentional delivery of miRNAs of interest through exosomes. As described above, physiological conditions and cell type alter the composition of exosomes secreted [27,28,103]. This process of altering cellular conditions to change cellular gene expression, and therefore exosome compositions, is termed "preconditioning" [26].…”

“…Exosomes carry a wide expanse of miRNAs responsible for various processes, including signal transduction, self-antigen presentation on MHCIs, intercellular adhesion markers, and surface markers [54]. Other methods of interaction with receptor cells include receptor-ligand interaction; lipid-raft, caveolae, receptor, and clathrin-mediated endocytosis; micropinocytosis, and phagocytosis [103]. Manipulation of these sorting, signaling, and identification characteristics are potential opportunities for modification of exosomes function and reception by receptor cells [54].…”

“…Methods to manipulate exosome content can target the exosomes directly or the cell-secreting exosomes [112]. Direct methods of exosome loading include simple incubation with the target molecule, electroporation [44], and saponin permeabilization to increase membrane permeability and optimize target entry into exosome, and chemical conjugation of the target molecule (transfection) with agents such as lipofectamine to increase entry through the membrane [103]. Direct transfection of BM-MSC exosomes with miR19a/19b conferred increased cardiac recovery and decreased cardiac fibrosis compared to non-enriched BM-MSC exosomes in a mouse model [113].…”

Chimeric Oncolytic Adenovirus Armed Chemokine Rantes for Treatment of Breast Cancer

“…Tumor immunotherapy, such as PD-1/PD-L1, CTLA-4 antibody therapy and CAR-T/CAR-NK immune cell therapy, is based on the activation of immune cells, especially T cells, which can kill cancer cells [ 21 , 22 ]. For solid tumors, the number of formerly-owned and lately-migrated immune cells in the TME is very small, which is the difficulty of immunotherapy for solid tumors [ 23 ].…”