title: Heparin-folate-retinoic acid bioconjugates for targeted delivery of hydrophobic photosensitizers.
abstract: Amphiphilic heparin-retinoic acid (HR) and heparin-folate-retinoic acid bioconjugates (HFR) were synthesized by chemical conjugation of a hydrophobic anticancer agent all-trans-retinoic acid (RA) and a targeting ligand, folic acid (FA), to the high molecular weight heparin backbone. The HR and HFR bioconjugates had a high RA content (22%, w/w) and could self-assemble into nanoparticles with efficient encapsulation of a hydrophobic photosensitizer, pheophorbide a (PhA). The HFR bioconjugate demonstrated higher PhA loading content and loading efficiency compared to HR bioconjugate. The PhA-loaded HR and HFR nanoparticles had an average diameter of about 70 nm, a negatively charged surface, a sustained release pattern and self-quenching effect in a buffered solution. Furthermore, the cellular uptake of PhA-loaded HFR nanoparticles in folate receptor-positive HeLa cells was higher than that of PhA-loaded HR nanoparticles. Upon irradiation, HFR nanoparticles selectively enhanced the phototoxicity of PhA in HeLa cells while the dark-toxicity of the nanoparticles was minimal without light treatment. HFR nanoparticles also demonstrated targeted anti-cancer effect, improving the cytotoxicity of RA in HeLa cells compared to HR nanoparticles at RA concentration ≥50 μg/mL. The targeting effect of HFR and PhA-loaded HFR nanoparticles was not observed in folate receptor-negative HT-29 cells. The results indicated that HFR nanoparticles may be useful for targeted delivery of hydrophobic PDT agents and as a potential nanocarrier for dual chemo-and photodynamic therapies.
authors: Department of Polymer Science & Engineering, Chungnam National University, 220, Gung-dong, Yuseng-gu, Daejeon 305-764, Republic of Korea.
authors: Thanh Huyen
authors: TH
authors: Tran
authors: Byoung-chan
authors: BC
authors: Bae
authors: Yong-kyu
authors: YK
authors: Lee
authors: Kun
authors: K
authors: Na
authors: Kang Moo
authors: KM
authors: Huh
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001692:Biological Transport; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry*; D019073:HT29 Cells; D006367:HeLa Cells; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000737:chemistry; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D026082:Singlet Oxygen / Q000737:chemistry; D014212:Tretinoin / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D017319:Photosensitizing Agents; D002734:Chlorophyll; D026082:Singlet Oxygen; D014212:Tretinoin; D006493:Heparin; D005492:Folic Acid; C032623:pheophorbide a