title: Degradable Polyethylenimine-Based Gene Carriers for Cancer Therapy.
abstract: Gene therapy using recombinant DNA or gene silencing using siRNA have become a prominent area of research in cancer therapy. However, their use in clinical applications is limited due to overall safety concerns and suboptimal efficacy. Although non-viral vectors such as polycationic polymers do not offer the same level of transfection efficiency as their viral counterparts, they still demonstrate immense potential as alternatives to viral vectors, given their versatility, low immunogenicity, ease of large-scale production, and ability to accelerate gene transfer with well-designed delivery platforms. Among these polymers, polyethylenimine (PEI) is considered a state-of-the-art gene carrier, owing to its ability to improve gene transfer capacity and intracellular delivery. Nonetheless, PEI suffers from the critical shortcoming of non-degradability that can lead to severe cytotoxic effects, despite the fact that the level of this toxicity decreases with molecular weight (MW). As a result, a considerable amount of effort has been devoted to designing low-MW PEI derivatives with degradable linkages. This review will categorize the recent advances in these degradable PEI derivatives based on their degradable chemistries, including ester, disulfide, imine, carbamate, amide, and ketal linkages, and summarize their application in gene therapies against various major cancer malignancies.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Jiang
authors.affiliation: Center for Nanomedicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Mohammad Ariful
authors.initials: MA
authors.lastname: Islam
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xing
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Jannatul
authors.initials: J
authors.lastname: Firdous
authors.affiliation: Nanotechnology Engineering Program, University of Waterloo, Waterloo, Canada.
authors.forename: Wuji
authors.initials: W
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: He
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Plastic Surgery, Institute of Dermatology and Plastic Surgery, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA.
authors.forename: Ki-Hyun
authors.initials: KH
authors.lastname: Cho
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
authors.forename: Hui-Shan
authors.initials: HS
authors.lastname: Li
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea. chocs@snu.ac.kr.
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
mesh_terms: D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D009369:Neoplasms / Q000628:therapy*; D011094:Polyethyleneimine / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011094:Polyethyleneimine
keywords: Biodegradability; Cancer therapy; Gene delivery; PEI derivatives