Exosomes as a Drug Delivery System in Cancer Therapy: Potential and Challenges

Abstract

Exosomes play a pivotal role in mediating intercellular communications and package delivery. They have recently been discovered to serve as diagnostic biomarkers as well as a possible drug delivery vehicle based on their nanometer size range and capability to transfer biological materials to recipient cells. Their unique biocompatibility, high stability, preferred tumor homing, and adjustable targeting efficiency can make exosomes an attractive and potentially effective tool of drug delivery in cancer therapy. While exosomes possess properties that make them uniquely suitable for delivery of bioactive molecules, there remains a to-be-filled gap between the current understanding about exosome biology and the ideal application scenarios. In this review, we summarize the characteristics enabling the potential of exosomes for drug delivery as well as the outstanding questions related to exosome composition and function, production and purification, bioengineering and targeting, uptake and biodistribution, efficacy and immune regulation, etc. Advanced technologies are demanded to visualize, characterize, and sort heterogeneous exosome populations. We are positive that the deeper and more comprehensive understanding of exosome biology as well as advanced nanotechnology will certainly accelerate its therapeutic applications.

Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer

“…[49,50] Recently, extracellular vesicles (EVs) or exosomes have attracted considerable attention due their ability to target many cancers. [51][52][53] There are several advantages to using macrophages as a delivery vehicle in comparison to exosomes. Exosomes can be loaded relatively well with proteins, [54][55][56] but loading with nucleic acids is considerably more difficult due to aggregation and charge.…”

Microfluidic On-demand Engineering of Exosomes towards Cancer Immunotherapy

“…Current immunotherapy treatments can only benefit less than 15 % of patients, due to the poorly understood immunity modulation mechanism, and the lack of well-targeted delivery and clinical study designs that are optimized to determine maximum efficacy [61][62][63][64] . Immune cell-derived exosomes can be powerful vaccine templates for transferring stimulating factors, antigens, and drugs, which is highly promising by utilizing patientderived exosomes for developing personalized precision cancer vaccination 40,[65][66][67][68][69] . Our developed microfluidic platform could serve as the powerful technology platform for facilitating this discovery in personalized cancer vaccines.…”

<p>Extracellular Vesicles As Nanomedicine: Hopes And Hurdles In Clinical Translation</p>

“…78,79 Drug-loaded EVs physiologically decorated with functionally reactive membrane markers are expected to exert preferential tumor-homing capacities and thus to outperform synthetic nanocarriers with limited mean capacities (<1%) 80 as delivery packages to solid tumors. 5,81 An essential question is the selection of parent cells best suited for clinical-grade EV generation and drug loading. So far, experimental, preclinical, and clinical evaluations involve diverse cellular sources, including dendritic cells, autologous tumor cells, cancer cell lines, ascites, macrophages, and plants.…”

“…So far, experimental, preclinical, and clinical evaluations involve diverse cellular sources, including dendritic cells, autologous tumor cells, cancer cell lines, ascites, macrophages, and plants. 5,76,81 Loaded drugs have included doxorubicin, paclitaxel, curcumin, cisplatin, and methotrexate. 76 Various options exist for drug loading in EVs, as recently reviewed.…”