title: Cancer targeting with biomolecules: a comparative study of photodynamic therapy efficacy using antibody or lectin conjugated phthalocyanine-PEG gold nanoparticles.
abstract: The functionalisation of therapeutic nanoparticle constructs with cancer-specific biomolecules can enable selective tumour accumulation and targeted treatment. Water soluble gold nanoparticles (ca. 4 nm) stabilised by a mixed monolayer of a hydrophobic zinc phthalocyanine photosensitiser (C11Pc) and hydrophilic polyethylene glycol (PEG) have been prepared. The C11Pc-PEG gold nanoparticle constructs were further functionalised with jacalin, a lectin specific for the cancer-associated Thomsen-Friedenreich (T) carbohydrate antigen, or with monoclonal antibodies specific for the human epidermal growth factor receptor-2 (HER-2). The two biofunctionalised nanoparticle conjugates produced similar levels of singlet oxygen upon irradiation at 633 nm. Importantly, both nanoparticle conjugates demonstrated extensive, yet comparable, phototoxicity in HT-29 colorectal adenocarcinoma cells (80-90%) and in SK-BR-3 breast adenocarcinoma cells (>99%). Non-conjugated C11Pc-PEG gold nanoparticles were only minimally phototoxic. Lysosomal colocalisation studies performed with the HT-29 colon cancer cells and the SK-BR-3 breast cancer cells revealed that both nanoparticle conjugates were partially localised within acidic organelles, which is typical of receptor-mediated endocytosis. The similarity of the targeted PDT efficacy of the two biofunctionalised C11Pc-PEG gold nanoparticles is discussed with respect to targeting ligand binding affinity and cell surface antigen density as key determinants of targeting efficiency. This study highlights how targeting small cell-surface molecules, such as the T antigen, can mediate a selective photodynamic treatment response which is similar to that achieved when targeting overexpressed protein receptors, such as HER-2. The high prevalence of the T antigen present on the cellular surface of primary tumours emphasises the broad potential applications for lectin-targeted therapies.
authors.affiliation: School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, UK. d.russell@uea.ac.uk.
authors.forename: Girgis
authors.initials: G
authors.lastname: Obaid
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chambrier
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cook
authors.forename: David A
authors.initials: DA
authors.lastname: Russell
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000737:chemistry; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017612:Gold Compounds / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D054833:Isoindoles; D037102:Lectins / Q000737:chemistry / Q000627:therapeutic use; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy / Q000379:methods*; D009942:Organometallic Compounds / Q000737:chemistry / Q000627:therapeutic use*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D026082:Singlet Oxygen / Q000737:chemistry; D017967:Zinc Compounds
chemical_list: D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D000970:Antineoplastic Agents; D017612:Gold Compounds; D007211:Indoles; D054833:Isoindoles; D037102:Lectins; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; D026082:Singlet Oxygen; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; C013647:phthalocyanine