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Gemcitabine loaded autologous exosomes for effective and safe chemotherapy of pancreatic cancer.

Abstract

Pancreatic cancer remains one of the most highly lethal diseases with very poor prognosis. Gemcitabine (GEM) is the first-line chemotherapeutic drug for pancreatic cancer treatment but is associated with significant side effects when administered systemically. Exosomes have emerged as attractive candidates for drug delivery for their high delivery efficiency and biocompatibility. Here, GEM was loaded into autologous exosomes to formulate ExoGEM for targeted chemotherapy of pancreatic cancer. Autologous exosomes facilitate cellular uptake of GEM and contributed to significantly increased cytotoxic effect of GEM, while heterologous cellular uptake showed less efficiency. Autologous exosomes showed targeting ability to pancreatic cancer in biodistribution study, and GEM concentration in tumor site was increased via ExoGEM delivery. ExoGEM treatment, in tumor-bearing mice, significantly suppressed tumor growth, with prolonged survival in a dose-response manner, but caused minimal damage to normal tissues. More importantly, tumors in several mice treated with ExoGEM were disappeared without recurrence. Autologous exosomes are safe and effective vehicles for targeted delivery of GEM against pancreatic cancer. This delivery strategy may have implications for personalized chemotherapy of pancreatic cancer. STATEMENT OF

SIGNIFICANCE:

Exosomes are efficient delivery vehicles in intracellular communication. Moreover, potential tropism of autologous exosomes to the tumor microenvironment make them competitive delivery vehicles. The use of cancer-derived exosomes for drug delivery and superior targeting efficacy and enhanced anticancer efficacy of therapeutics have been evidenced. Gemcitabine is a mainstay for pancreatic treatment. However, poor cellular uptake and low targeting effects of gemcitabine often lead to severe systemic toxicity. Therefore, to overcome this limitation, we herein loaded gemcitabine into autologous pancreatic cancer-derived exosomes for the targeted chemotherapy of pancreatic cancer.

Authors+Show Affiliations

Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan, China; Hunan Provincial Engineering Research Center of Translational Medicine and Innovative Drug, Changsha, Hunan, China.Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan, China; Hunan Provincial Engineering Research Center of Translational Medicine and Innovative Drug, Changsha, Hunan, China.Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan, China; Hunan Provincial Engineering Research Center of Translational Medicine and Innovative Drug, Changsha, Hunan, China.Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan, China; Hunan Provincial Engineering Research Center of Translational Medicine and Innovative Drug, Changsha, Hunan, China.Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan, China; Hunan Provincial Engineering Research Center of Translational Medicine and Innovative Drug, Changsha, Hunan, China.Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan, China; Hunan Provincial Engineering Research Center of Translational Medicine and Innovative Drug, Changsha, Hunan, China. Electronic address: xiangdaxiong@csu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31629893

Citation

Li, Yong-Jiang, et al. "Gemcitabine Loaded Autologous Exosomes for Effective and Safe Chemotherapy of Pancreatic Cancer." Acta Biomaterialia, 2019.
Li YJ, Wu JY, Wang JM, et al. Gemcitabine loaded autologous exosomes for effective and safe chemotherapy of pancreatic cancer. Acta Biomater. 2019.
Li, Y. J., Wu, J. Y., Wang, J. M., Hu, X. B., Cai, J. X., & Xiang, D. X. (2019). Gemcitabine loaded autologous exosomes for effective and safe chemotherapy of pancreatic cancer. Acta Biomaterialia, doi:10.1016/j.actbio.2019.10.022.
Li YJ, et al. Gemcitabine Loaded Autologous Exosomes for Effective and Safe Chemotherapy of Pancreatic Cancer. Acta Biomater. 2019 Oct 18; PubMed PMID: 31629893.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gemcitabine loaded autologous exosomes for effective and safe chemotherapy of pancreatic cancer. AU - Li,Yong-Jiang, AU - Wu,Jun-Yong, AU - Wang,Jie-Min, AU - Hu,Xiong-Bin, AU - Cai,Jia-Xin, AU - Xiang,Da-Xiong, Y1 - 2019/10/18/ PY - 2019/06/06/received PY - 2019/09/19/revised PY - 2019/10/15/accepted PY - 2019/10/21/pubmed PY - 2019/10/21/medline PY - 2019/10/21/entrez KW - Biocompatibility KW - Chemotherapy KW - Drug delivery KW - Exosomes KW - Gemcitabine KW - Pancreatic cancer JF - Acta biomaterialia JO - Acta Biomater N2 - Pancreatic cancer remains one of the most highly lethal diseases with very poor prognosis. Gemcitabine (GEM) is the first-line chemotherapeutic drug for pancreatic cancer treatment but is associated with significant side effects when administered systemically. Exosomes have emerged as attractive candidates for drug delivery for their high delivery efficiency and biocompatibility. Here, GEM was loaded into autologous exosomes to formulate ExoGEM for targeted chemotherapy of pancreatic cancer. Autologous exosomes facilitate cellular uptake of GEM and contributed to significantly increased cytotoxic effect of GEM, while heterologous cellular uptake showed less efficiency. Autologous exosomes showed targeting ability to pancreatic cancer in biodistribution study, and GEM concentration in tumor site was increased via ExoGEM delivery. ExoGEM treatment, in tumor-bearing mice, significantly suppressed tumor growth, with prolonged survival in a dose-response manner, but caused minimal damage to normal tissues. More importantly, tumors in several mice treated with ExoGEM were disappeared without recurrence. Autologous exosomes are safe and effective vehicles for targeted delivery of GEM against pancreatic cancer. This delivery strategy may have implications for personalized chemotherapy of pancreatic cancer. STATEMENT OF SIGNIFICANCE: Exosomes are efficient delivery vehicles in intracellular communication. Moreover, potential tropism of autologous exosomes to the tumor microenvironment make them competitive delivery vehicles. The use of cancer-derived exosomes for drug delivery and superior targeting efficacy and enhanced anticancer efficacy of therapeutics have been evidenced. Gemcitabine is a mainstay for pancreatic treatment. However, poor cellular uptake and low targeting effects of gemcitabine often lead to severe systemic toxicity. Therefore, to overcome this limitation, we herein loaded gemcitabine into autologous pancreatic cancer-derived exosomes for the targeted chemotherapy of pancreatic cancer. SN - 1878-7568 UR - https://www.unboundmedicine.com/medline/citation/31629893/Gemcitabine_loaded_autologous_exosomes_for_effective_and_safe_chemotherapy_of_pancreatic_cancer L2 - https://linkinghub.elsevier.com/retrieve/pii/S1742-7061(19)30701-9 DB - PRIME DP - Unbound Medicine ER -