title: A novel multifunctional poly(amidoamine) dendrimeric delivery system with superior encapsulation capacity for targeted delivery of the chemotherapy drug 10-hydroxycamptothecin.
abstract: With the aim of developing an efficient targeted delivery system for cancer therapy that overcomes drug leakage during circulation, we prepared a novel multifunctional dendrimeric carrier by integrating long hydrophobic C₁₂ alkyl chains, poly(ethylene glycol) chains and c(RGDfK) ligands presented on the surface. This dendrimer was able to tightly encapsulate the hydrophobic anticancer drug 10-hydroxycamptothecin (10-HCPT) through simple complexation and selectively target the drug to cancer cells overexpressing integrin αvβ₃ through high affinity interactions. The complex has a high loading efficiency, with each molecule encapsulating approximately 20 drug molecules; high stability, without any detectable drug release during dialysis for three days; and high water solubility, achieving an approximately 600-fold increase over the water solubility of free 10-HCPT. This complex exhibited notably high cytotoxicity against 22RV1 cells overexpressing integrin αvβ₃ and a far lower cytotoxicity against MCF-7 cells, which express low levels of integrin αvβ₃. We expected encapsulated 10-HCPT to regain its anti-cancer activity following selective internalization of the complex into carcinoma cells via integrin receptor mediated endocytosis. As the drug remains inactive before internalization, this carrier has the ability to overcome problems associated with drug leakage in the circulation and off-target effects on normal tissues.
authors: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors: Xiuqi
authors: X
authors: Kong
authors: College of Material Science and Chemical Engineering, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors: Kui
authors: K
authors: Yu
authors: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors: Min
authors: M
authors: Yu
authors: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors: Yupeng
authors: Y
authors: Feng
authors: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors: Jin
authors: J
authors: Wang
authors: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors: Mingjie
authors: M
authors: Li
authors: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors: Zeming
authors: Z
authors: Chen
authors: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors: Minghao
authors: M
authors: He
authors: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors: Rui
authors: R
authors: Guo
authors: College of Material Science and Chemical Engineering, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors: Ruisong
authors: R
authors: Tian
authors: College of Material Science and Chemical Engineering, Tianjin University of Science and Technology, Tianjin 300457, PR China.
authors: Yuxi
authors: Y
authors: Li
authors: College of Material Science and Chemical Engineering, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address: wwjie@tust.edu.cn.
authors: Wenjie
authors: W
authors: Wu
authors: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, PR China. Electronic address: hongzy@nankai.edu.cn.
authors: Zhangyong
authors: Z
authors: Hong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D050091:Dendrimers / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D004705:Endocytosis; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007700:Kinetics; D061986:MCF-7 Cells; D008297:Male; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism; D011073:Polyamines / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050091:Dendrimers; D004337:Drug Carriers; D039302:Integrin alphaVbeta3; C104700:PAMAM Starburst; D010456:Peptides, Cyclic; C531249:Poly(amidoamine); D011073:Polyamines; C099250:cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl); C028098:10-hydroxycamptothecin; D002166:Camptothecin
keywords: 10-Hydroxycamptothecin; 10-Hydroxycamptothecin (PubChem CID: 97226); Encapsulation; Integrin; Multifunctional dendrimers; Targeted cancer therapy