Targeted photodynamic therapy of breast cancer cells using lactose-phthalocyanine functionalized gold nanoparticles

Abstract

Gold nanoparticles (AuNPs), which have been widely used for the delivery of photosensitizers for photodynamic therapy (PDT) of cancer, can be dispersed in aqueous solutions improving the delivery of the hydrophobic photosensitizer into the body. Furthermore, the large surface of AuNPs can be functionalized with a variety of ligands, including proteins, nucleic acids and carbohydrates, that allow selective targeting to cancer tissue. In this study, gold nanoparticles were functionalized with a mixed monolayer of a zinc phthalocyanine and a lactose derivative. For the first time, a carbohydrate was used with a dual purpose, as the stabilizing agent of the gold nanoparticles in aqueous solutions and as the targeting agent for breast cancer cells. The functionalization of the phthalocyanine-AuNPs with lactose led to the production of water-dispersible nanoparticles that are able to generate singlet oxygen and effect cell death upon irradiation. The targeting ability of lactose of the lactose-phthalocyanine functionalized AuNPs was studied in vitro towards the galectin-1 receptor on the surface of breast cancer cells. The targeting studies showed the exciting potential of lactose as a specific targeting agent for galactose-binding receptors overexpressed on breast cancer cells.

Flow-induced Shear Stress Confers Resistance to Carboplatin in an Adherent Three-Dimensional Model for Ovarian Cancer: A Role for EGFR-Targeted Photoimmunotherapy Informed by Physical Stress

“…PDT can help decrease solid stress and, thereby, modulate microenvironmental factors that influence tumor growth and treatment response, such as hypoxia and interstitial fluid pressure [139][140][141][142][143][144]. To improve selective delivery, the PS can be attached to a variety of targeting moieties, such as carbohydrates, peptides, folic acid and antibodies, or nanocarriers that target markers that are overexpressed on cancer cells [48,97,136,[145][146][147][148][149]. PIT involves the use of an antibody-based PIC to enhance PS selectivity and has been shown to be effective in a variety of cancer types, including ovarian cancer [49,60,61,[67][68][69][70][94][95][96][97].…”

Photodynamic Therapy and the Biophysics of the Tumor Microenvironment

“…However, in vivo studies showed that M-chlorin PDT led to significantly more tumor suppression than G-chlorin PDT, which was attributed to the affinity of M-chlorin for CD-206 expressing TAMs in addition to cancer cells. These results suggest exciting opportunities for future studies that target multiple (327)(328)(329)(330) cell types with a single targeting moiety to achieve enhanced antitumor effect. Such constructs could potentially achieve synergistic cytotoxicity by killing cancer cells as well as the nonmalignant cells that contribute to tumor maintenance, thereby providing an inherent mechanism for managing the cancer cells that survive initial treatment.…”

“…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.…”

“…8a). Targeting moieties used for this purpose include folic acid, peptides, antibodies and carbohydrates (325)(326)(327)(328)(329)(330)(331)(332)(333)(334)(335)(336)(337)(338) (Table 3), and can be either conjugated to a nanoparticle or directly to a PS. Most PDT treatments that incorporate such targeting moieties are designed to directly target cancer cells.…”

Towards optimisation of surface enhanced photodynamic therapy of breast cancer cells using gold nanoparticle-photosensitiser conjugates

“…One ZnPc is connected via three carbon atoms (C3Pc), whereas the other is connected via eleven (C11Pc) (Fig 1). 23 In solution, the C11Pc photosensitiser exhibited significantly greater fluorescence than the C3Pc. Intriguingly, despite the shorter anchor chain and the expectant quenching of the fluorescence of the C3Pc photosensitiser, the C3Pc was found to be more fluorescent when attached to the surface of the AuNPs than the C11Pc with the longer chain.…”