Naphthalocyanine-reconstituted LDL nanoparticles for in vivo cancer imaging and treatment.
Low density lipoproteins (LDLs) are naturally occurring nanoparticles that are biocompatible, biodegradable and non-immunogenic. Moreover, the size of LDL particle is precisely controlled (approximately 22 nm) by its apoB-100 component, setting them apart from liposomes and lipid micelles. LDL particles have long been proposed as a nanocarrier for targeted delivery of diagnostics and therapeutics to LDL receptor (LDLR)-positive cancers. Here, we report the design and synthesis of a novel naphthalocyanine (Nc)-based photodynamic therapy (PDT) agent, SiNcBOA, and describe its efficient reconstitution into LDL core (100:1 payload). Possessing a near-infrared (NIR) absorption wavelength (> 800 nm) and extremely high extinction coefficient (> 10(5) M(-1)cm(-1)), SiNcBOA holds the promise of treating deeply seated tumors. Reconstituted LDL particles (r-Nc-LDL) maintain the size and shape of native LDL as determined by transmission electron microscopy, and also retain their LDLR-mediated uptake by cancer cells as demonstrated by confocal microscopy. Its preferential uptake by tumor vs normal tissue was confirmed in vivo by noninvasive optical imaging technique, demonstrating the feasibility of using this nanoparticle for NIR imaging-guided PDT of cancer.
Song
Liping
L
Department of Chemistry, Shanghai University, China.
Li
Hui
H
Sunar
Ulas
U
Chen
Juan
J
Corbin
Ian
I
Yodh
Arjun G
AG
Zheng
Gang
G
D000818:Animals; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D018197:Hepatoblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D054833:Isoindoles; D008077:Lipoproteins, LDL / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
D004337:Drug Carriers; D007211:Indoles; D054833:Isoindoles; D008077:Lipoproteins, LDL; D017319:Photosensitizing Agents; C013647:phthalocyanine