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Theranostics 2022; 12(3):1030-1060. doi:10.7150/thno.64805 This issue Cite

Review

Nanocarriers for pancreatic cancer imaging, treatments, and immunotherapies

Luman Liu^1#, Prakash G. Kshirsagar^2#, Shailendra K. Gautam^2#, Mansi Gulati^2#, Emad I. Wafa³, John C. Christiansen⁴, Brianna M. White¹, Surya K. Mallapragada^1,5, Michael J. Wannemuehler^4,5, Sushil Kumar², Joyce C. Solheim^2,5,6,7, Surinder K. Batra^2,5,6,7, Aliasger K. Salem^3,5✉, Balaji Narasimhan^1,5✉, Maneesh Jain^2,5,7✉

1. Department of Chemical and Biological Engineering, Iowa State University, Ames, IA.
2. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha NE.
3. Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA.
4. Department of Veterinary Microbiology & Preventive Medicine, Iowa State University, Ames, IA.
5. Nanovaccine Institute, Iowa State University, Ames, IA.
6. Eppley Institute, University of Nebraska Medical Center, Omaha, NE.
7. Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha NE.
#These authors contributed equally to this work.

✉ Corresponding authors: Maneesh Jain, Ph.D., E-mail: mjainedu, Phone: 402-559-7667; Balaji Narasimhan, Ph.D., E-mail: nbalajiedu, Phone: 515-294-8019; Aliasger K. Salem, Ph. D., E-mail: aliasger-salemedu, Phone: 319-335-8796.

Abstract

Pancreatic tumors are highly desmoplastic and immunosuppressive. Delivery and distribution of drugs within pancreatic tumors are compromised due to intrinsic physical and biochemical stresses that lead to increased interstitial fluid pressure, vascular compression, and hypoxia. Immunotherapy-based approaches, including therapeutic vaccines, immune checkpoint inhibition, CAR-T cell therapy, and adoptive T cell therapies, are challenged by an immunosuppressive tumor microenvironment. Together, extensive fibrosis and immunosuppression present major challenges to developing treatments for pancreatic cancer. In this context, nanoparticles have been extensively studied as delivery platforms and adjuvants for cancer and other disease therapies. Recent advances in nanotechnology have led to the development of multiple nanocarrier-based formulations that not only improve drug delivery but also enhance immunotherapy-based approaches for pancreatic cancer. This review discusses and critically analyzes the novel nanoscale strategies that have been used for drug delivery and immunomodulation to improve treatment efficacy, including newly emerging immunotherapy-based approaches. This review also presents important perspectives on future research directions that will guide the rational design of novel and robust nanoscale platforms to treat pancreatic tumors, particularly with respect to targeted therapies and immunotherapies. These insights will inform the next generation of clinical treatments to help patients manage this debilitating disease and enhance survival rates.

Keywords: Pancreatic ductal adenocarcinoma, solid tumors, nanoparticles, drug delivery, immunotherapy, tumor microenvironment

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