Extracellular vesicles: emerging anti-cancer drugs and advanced functionalization platforms for cancer therapy

Abstract

Increasing evidences show that unmodified extracellular vesicles (EVs) derived from various cells can effectively inhibit the malignant progression of different types of tumors by delivering the bioactive molecules. Therefore, EVs are expected to be developed as emerging anticancer drugs. Meanwhile, unmodified EVs as an advanced and promising nanocarrier that is frequently used in targeted delivery therapeutic cargos and personalized reagents for the treatment and diagnosis of cancer. To improve the efficacy of EV-based treatments, researchers are trying to engineering EVs as an emerging nanomedicine translational therapy platform through biological, physical and chemical approaches, which can be broaden and altered to enhance their therapeutic capability. EVs loaded with therapeutic components such as tumor suppressor drugs, siRNAs, proteins, peptides, and conjugates exhibit significantly enhanced anti-tumor effects. Moreover, the design and preparation of tumor-targeted modified EVs greatly enhance the specificity and effectiveness of tumor therapy, and these strategies are expected to become novel ideas for tumor precision medicine. This review will focus on reviewing the latest research progress of functionalized EVs, clarifying the superior biological functions and powerful therapeutic potential of EVs, for researchers to explore new design concepts based on EVs and build next-generation nanomedicine therapeutic platforms.

Keywords: Engineered EVs; bioinspiration; cancer therapy; drug delivery; functionalization strategy.

Figure 1.

The biogenesis, release and uptake of EVs and their interactions with target cells. The biosynthesis and regulatory mechanisms of different types of secreted EVs. Three major mechanisms have been suggested to mediate the uptake of EVs, including cell membrane fusion, receptor-ligand interactions and endocytosis.

Figure 2.

The overall compisition of EVs. The main components of EVs include nucleic acids, proteins, lipids and metabolites. Main classification of nucleic acids and proteins components enriched in EVs that mediates the intercellular communication between different cell types in the body, thus affecting the normal and pathological stateand their potential biological functions.

Figure 3.

MSCs derived EVs for cancer therapy. The EVs derived from MSCs carry a variety of bioactive molecules that play an effective anti-tumor efficacy in various cancer diseases. EVs derived from MSCs are also ideal candidates for engineered EVs.

Figure 4.

Other Mammalian cells derived EVs for cancer therapy. The EVs derived from tumor cells and main immune cells carry a variety of bioactive molecules that play an effective anti-tumor efficacy in various cancer diseases. EVs derived from tumor cells and DC cells mainly induce specific humoral and cellular immune responses in the body, enhance the anticancer ability of the body and prevent the growth of tumors. M1-type macrophages are derived from EVs polarized M2-type macrophages into anti-tumor M1-type macrophages and release inflammatory cytokines to play a role in tumor therapy. EVs from NK cells and T cells play a therapeutic role by releasing tumor-killing molecules and cytotoxic effects.

Figure 5.

Source of functionalized EVs. EVs can be produced by almost all prokaryotic and eukaryotic, and plant cells, and are widely present in body fluids such as blood, urine, ascites and milk, etc.

Figure 6.

Functionalized approchs of EVs. Traditional bio-techniques and advanced nanotechnologies have been generalized in the engineering modification of EVs. These methods are divided into two main categories: membrane modification and content loading.

Figure 7.

Functionalized EVs for cancer therapy. Currently, the application of Functionalized EVs in cancer therapy has five main directions, including chemotherapy, gene therapy, immunotherapy, phototherapy, and vaccine development.