Cancer Cell-Derived, Drug-Loaded Nanovesicles Induced by Sulfhydryl-Blocking for Effective and Safe Cancer Therapy.
Dominique IngatoJulius A EdsonMichael ZakharianYoung Jik KwonPublished in: ACS nano (2018)
Extracellular vesicles (EVs) pose great promise as therapeutic carriers due to their ideal size range and intrinsic biocompatibility. Limited scalability, poor quality control during production, and cumbersome isolation and purification processes have caused major setbacks in the progression of EV therapeutics to the clinic. Here, we overcome these setbacks by preparing cell-derived nanovesicles induced by sulfhydryl-blocking (NIbS), in the desirable size range for therapeutic delivery, that can be further loaded with the chemotherapeutic drug, doxorubicin (DOX), resulting in NIbS/DOX. Applicable to most cell types, this chemical blebbing approach enables efficient, quick, and simple harvest and purification as well as easily scalable production. Cellular uptake and intracellular release of DOX was improved using NIbS/DOX compared to a liposomal formulation. We also confirmed that in tumor-challenged C57BL/6 mice NIbS/DOX significantly slowed tumor growth and led to improved survival compared to treatment with free drug or liposomal drug. NIbS are a promising therapeutic carrier for improving cancer treatment outcomes since they are easy to prepare at a large scale, good candidates for drug loading, and capable of efficient administration of therapeutic agents with avoided nonspecific major distribution in vital organs. In addition, the utility of NIbS can be easily expanded to immunotherapy, gene therapy, and cell therapy when they are derived from applicable cell types.
Keyphrases
- cell therapy
- cancer therapy
- drug delivery
- gene therapy
- quality control
- papillary thyroid
- adverse drug
- single cell
- primary care
- stem cells
- squamous cell carcinoma
- drug induced
- type diabetes
- squamous cell
- metabolic syndrome
- skeletal muscle
- machine learning
- young adults
- big data
- bone marrow
- wound healing
- electronic health record
- wild type