Effects of poly(ethylene glycol) grafting density on the tumor targeting efficacy of nanoparticles with ligand modification.
To evaluate the effects of poly(ethylene glycol) (PEG) grafting density on the tumor targeting efficacy of nanoparticles (NPs) with ligand modification, various amounts of PEG were conjugated to linoleic acid and poly(β-malic acid) double grafted chitosan (LMC) NPs bearing similar substitution degree of folate (FA). Increased particle size, decreased surface charge, reduced contact angle, retarded drug release and suppressed protein adsorption of LMC NPs were detected after surface modification. Compared to LMC NPs, FA-modified LMC NPs (FA-LMC NPs) remarkably enhanced tumor specificity. For PEG-modified FA-LMC NPs, increased drug accumulation in tumor tissues and reduced cellular uptake were observed with the increase of PEG grafting density. In regard to in vivo antitumor efficacy, FA-LMC NPs with moderate PEG grafting density (8.9%) significantly outperformed FA-LMC NP. Therefore, PEG modification with moderate grafting density could be a promising approach to coordinating with the tumor targeting efficacy of ligand-modified NPs.
State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University , Shanghai , China.
Shidong
S
Zhang
Cui
C
Tang
Chunhua
C
Yin
D000818:Animals; D021461:Animals, Outbred Strains; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D001692:Biological Transport; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D019787:Linoleic Acid / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D008293:Malates / Q000737:chemistry; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011897:Random Allocation; D013499:Surface Properties; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008024:Ligands; D008293:Malates; D011108:Polymers; C121060:poly(malic acid); D011092:Polyethylene Glycols; D048271:Chitosan; D005492:Folic Acid; D019787:Linoleic Acid; D017239:Paclitaxel
Grafting density; hydrophilic polymers; nanoparticles; surface modification; targeted delivery