title: pH-Triggered Surface Charge Reversed Nanoparticle with Active Targeting To Enhance the Antitumor Activity of Doxorubicin.
abstract: PLGA nanoparticles are widely used in tumor targeting drug delivery systems. However, the naked PLGA nanoparticles (NNPs) not only have low drug loading but also can be rapidly removed from blood circulation by the immune system. The aim of this study was to prepare pH-triggered surface charge reversed lipid hybrid PLGA nanoparticles (LNPs) to enhance drug loading and drug delivery efficiency. CHO-Arg-His-OMe and FA-PEG-DSPE were synthesized to modify PLGA nanoparticles to prepare LNPs. The drug loading and encapsulation rate of LNPs were greatly improved as compared with NNPs. In pH 7.4 medium, doxorubicin (DOX)-loaded LNPs showed negative charge and released DOX slowly. In pH 5.0 medium, DOX-loaded LNPs exhibited positive charge and released DOX quickly. DOX-loaded LNPs delivered more DOX to the nucleus of KB cells and MBA-MD-231/ADR cells than did free DOX. In addition, DOX-loaded LNPs significantly inhibited the proliferation of KB cells and MBA-MD-231/ADR cells. Compared with free DOX, the same dose of the DOX-loaded LNPs delivered more DOX to tumor tissue. Thus, DOX-loaded LNPs significantly inhibited the growth of tumor in tumor-bearing nude mice and obviously reduced the systemic toxicity of DOX. In conclusion, pH-triggered surface charge reversed DOX-loaded LNPs significantly enhanced the antitumor activity of DOX in vitro and in vivo. DOX-loaded LNPs had great potential in tumor targeted chemotherapy.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University , Xi'an, 710032, China.
authors.forename: Jiang-Bo
authors.initials: JB
authors.lastname: Du
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University , Xi'an, 710032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University , Xi'an, 710032, China.
authors.forename: Zeng-Hui
authors.initials: ZH
authors.lastname: Teng
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University , Xi'an, 710032, China.
authors.forename: Meng-Lei
authors.initials: ML
authors.lastname: Huan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University , Xi'an, 710032, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University , Xi'an, 710032, China.
authors.forename: Han
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University , Xi'an, 710032, China.
authors.forename: Bang-le
authors.initials: BL
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University , Xi'an, 710032, China.
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Zhou
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005492:Folic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007624:KB Cells; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010713:Phosphatidylcholines; C000594835:folic acid-poly(ethyleneglycol)-2-distearoylglycero-3-phosphoethanolamine; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin; D005492:Folic Acid
keywords: PLGA; doxorubicin; folate; lipid hybrid nanoparticles