title: Multifunctional drug delivery system for targeting tumor and its acidic microenvironment.
abstract: Effective targeting drug delivery for cancer therapy still remains a formidable challenge due to the complication and heterogeneity of malignant tumors. Herein, a multifunctional targeting strategy was proposed, in which a novel pH-sensitive polymethacrylates (PMA)-grafted poly(amidoamine) (PAMAM) nano delivery system was designed to be responsive to the acidic tumor microenvironment, and thereby trigger drug release in the intra-tumoral space. In addition, folate-PEGylation was applied to modify the surface of PMA-PAMAM nanoparticles in order to enhance tumor selectivity via both active and passive targeting mechanisms: folate receptor targeting, long circulation and EPR effect. The utility and efficacy of such system was demonstrated both in vitro and in vivo. Tumor drug accumulation was significantly enhanced by folate-PEGylated PMA-PAMAM nanoparticles, and such observation corresponded to their strong inhibition of tumor growth in tumor-bearing mice, demonstrating the success of the multifunctional targeting delivery. This multifunctional targeting strategy provides a promising solution to improve targeting drug delivery for combating the complex cancer diseases.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University; Key Lab of Smart Drug Delivery, Ministry of Education & PLA, Shanghai 201203, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shen
authors.forename: Yongzhuo
authors.initials: Y
authors.lastname: Huang
authors.forename: Limei
authors.initials: L
authors.lastname: Han
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Fang
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wang
authors.forename: Victor C
authors.initials: VC
authors.lastname: Yang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002460:Cell Line; D016503:Drug Delivery Systems; D005492:Folic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011073:Polyamines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011109:Polymethacrylic Acids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C531249:Poly(amidoamine); D011073:Polyamines; D011109:Polymethacrylic Acids; C030613:polymethacrylic acid; D011092:Polyethylene Glycols; D005492:Folic Acid; D017239:Paclitaxel