title: Comparative study of photosensitizer loaded and conjugated glycol chitosan nanoparticles for cancer therapy.
abstract: This study reports that tumor-targeting glycol chitosan nanoparticles with physically loaded and chemically conjugated photosensitizers can be used in photodynamic therapy (PDT). First, the hydrophobic photosensitizer, chlorin e6 (Ce6), was physically loaded onto the hydrophobically-modified glycol chitosan nanoparticles (HGC), which were prepared by self-assembling amphiphilic glycol chitosan-5β-cholanic acid conjugates under aqueous conditions. Second, the Ce6s were chemically conjugated to the glycol chitosan polymers, resulting in amphiphilic glycol chitosan-Ce6 conjugates that formed self-assembled nanoparticles in aqueous condition. Both Ce6-loaded glycol chitosan nanoparticles (HGC-Ce6) and Ce6-conjugated chitosan nanoparticles (GC-Ce6) had similar average diameters of 300 to 350 nm, a similar in vitro singlet oxygen generation efficacy under buffer conditions, and a rapid cellular uptake profile in the cell culture system. However, compared to GC-Ce6, HGC-Ce6 showed a burst of drug release in vitro, whereby 65% of physically loaded drugs were rapidly released from the particles within 6.5h in the buffer condition. When injected through the tail vein into tumor bearing mice, HGC-Ce6 did not accumulate efficiently in tumor tissue, reflecting the burst in the release of the physically loaded drug, while GC-Ce6 showed a prolonged circulation profile and a more efficient tumor accumulation, which resulted in high therapeutic efficacy. These comparative studies with drug-loaded and drug-conjugated nanoparticles showed that the photosensitizer-conjugated glycol chitosan nanoparticles with excellent tumor targeting properties have potential for PDT in cancer treatment.
authors: Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Haweolgog-Dong, Sungbook-Gu, Seoul 136-791, South Korea.
authors: So Jin
authors: SJ
authors: Lee
authors: Heebeom
authors: H
authors: Koo
authors: Hayoung
authors: H
authors: Jeong
authors: Myung Sook
authors: MS
authors: Huh
authors: Yongseok
authors: Y
authors: Choi
authors: Seo Young
authors: SY
authors: Jeong
authors: Youngro
authors: Y
authors: Byun
authors: Kuiwon
authors: K
authors: Choi
authors: Kwangmeyung
authors: K
authors: Kim
authors: Ick Chan
authors: IC
authors: Kwon
mesh_terms: D000818:Animals; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002735:Chlorophyllides; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D011166:Porphyrins / Q000008:administration & dosage*; D026082:Singlet Oxygen / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; C118638:glycol-chitosan; D026082:Singlet Oxygen; C062985:phytochlorin; D048271:Chitosan