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 2 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.

Water soluble, multifunctional antibody-porphyrin gold nanoparticles for targeted photodynamic therapy

“…In addition, targeting of the T antigen on the surface of human colorectal adenocarcinoma cells has been achieved using the lectin Jacalin conjugated to phthalocyanine functionalised gold nanoparticles. 22,23 Amongst the photosensitisers reported as useful for PDT, 3 porphyrins have been widely studied, especially since the development of the hematoporphyrin derivative,…”

Jacalin Has Chemopreventive Effects on Colon Cancer Development

“…Jacalin, a noncytotoxic lectin extracted from jackfruit (Artocarpus heterophyllus) seeds, specifically recognizes the Thomsen-Friedenreich antigen (TF-Gal β 1-3GalNAc), which is expressed in more than 85% of human carcinomas, and has antiproliferative effects on human colon cancer cells, highlighting its potential antitumor activity [9]. Over the last few years, jacalin has emerged as a candidate carrier for delivery of cancer therapeutics [10, 11]. However, to date, its in vivo direct antitumor activity has not been investigated.…”

Photodynamic Therapy and the Biophysics of the Tumor Microenvironment

“…a). Targeting moieties used for this purpose include folic acid, peptides, antibodies and carbohydrates (Table ), and can be either conjugated to a nanoparticle or directly to a PS.…”

“…The latter strategy was investigated in a study by Obaid et al . that compared using lectin for carbohydrate‐targeted nanoparticles with using antibodies for protein receptor‐targeted nanoparticles. To study this, gold nanoparticles were functionalized with either the lectin, jacalin or a monoclonal antibody.…”