A Drug-Eluting Injectable NanoGel for Localized Delivery of Anticancer Drugs to Solid Tumors
Brent Godau,
Sadaf Samimi,
Amir Seyfoori,
Ehsan Samiei,
Tahereh Khani,
Parvaneh Naserzadeh,
Alireza Hassani Najafabadi,
Emal Lesha,
Keivan Majidzadeh-A,
Behnaz Ashtari,
Gabriel Charest,
Christophe Morin,
David Fortin,
Mohsen Akbari
Affiliations
Brent Godau
Laboratory for Innovations in MicroEngineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, Canada
Sadaf Samimi
Laboratory for Innovations in MicroEngineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, Canada
Amir Seyfoori
Laboratory for Innovations in MicroEngineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, Canada
Ehsan Samiei
Laboratory for Innovations in MicroEngineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, Canada
Tahereh Khani
Preclinical Lab., Core Facility, Tehran University of Medical Sciences, Tehran 1417755354, Iran
Parvaneh Naserzadeh
Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran 88945173, Iran
Alireza Hassani Najafabadi
Terasaki Institute for Biomedical Innovations, Los Angeles, CA 90050, USA
Emal Lesha
Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Keivan Majidzadeh-A
Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, No. 146, South Gandhi Ave., Vanak Sq., P.O. BOX 1517964311, Tehran 1684613114, Iran
Behnaz Ashtari
Department of Medical Nanotechnology, Faculty of Advance Technologies in Medicine, Iran University of Medical Sciences, Tehran 1449614535, Iran
Gabriel Charest
Department of Surgery, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada
Christophe Morin
Department of Surgery, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada
David Fortin
Department of Surgery, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada
Mohsen Akbari
Laboratory for Innovations in MicroEngineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, Canada
Systemically administered chemotherapy reduces the efficiency of the anticancer agent at the target tumor tissue and results in distributed drug to non-target organs, inducing negative side effects commonly associated with chemotherapy and necessitating repeated administration. Injectable hydrogels present themselves as a potential platform for non-invasive local delivery vehicles that can serve as a slow-releasing drug depot that fills tumor vasculature, tissue, or resection cavities. Herein, we have systematically formulated and tested an injectable shear-thinning hydrogel (STH) with a highly manipulable release profile for delivering doxorubicin, a common chemotherapeutic. By detailed characterization of the STH physical properties and degradation and release dynamics, we selected top candidates for testing in cancer models of increasing biomimicry. Two-dimensional cell culture, tumor-on-a-chip, and small animal models were used to demonstrate the high anticancer potential and reduced systemic toxicity of the STH that exhibits long-term (up to 80 days) doxorubicin release profiles for treatment of breast cancer and glioblastoma. The drug-loaded STH injected into tumor tissue was shown to increase overall survival in breast tumor- and glioblastoma-bearing animal models by 50% for 22 days and 25% for 52 days, respectively, showing high potential for localized, less frequent treatment of oncologic disease with reduced dosage requirements.
