A novel strategy for targeting photodynamic therapy. Molecular combo of photodynamic agent zinc(ii) phthalocyanine and small molecule target-based anticancer drug erlotinib

Abstract

In this study, two phthalocyanine-erlotinib conjugates linked by an oligoethylene glycol chain have been synthesised and fully characterised. Having erlotinib as the targeting moiety, the two conjugates exhibited high specific affinity to HepG2 cancer cells and tumour tissues, therefore leading to high photodynamic activity.

Molecular‐Target‐Based Anticancer Photosensitizer: Synthesis and in vitro Photodynamic Activity of Erlotinib–Zinc(II) Phthalocyanine Conjugates

“…[4] The development of specifically targeted photosensitizers could greatly decrease the side effects of PDT. [22] For the latter, the complex structure and low stability of biomacromolecules consistently imposes difficulties in the preparation process, as well as changes-even losses-in biological activities during the modification process. [20,21] Although these two strategies have yielded promising results, they still face challenges.…”

“…Various approaches have been explored, including the use of nanoparticles modified with target moieties as delivery vehicles for photosensitizers, or conjugating photosensitizers to bio-macromolecules with targeting functions (antibodies, [5][6][7][8][9][10] peptides, [11][12][13] proteins, [14][15][16] and aptamers, [17][18][19] etc.). [22] For these reasons, a small molecular-target-based anticancer agent with a simple molecular structure and high stability would be a more suitable moiety for conjugation with a photosensitizer to achieve targeted PDT. For the former, the complex level of control required for nanoparticles in terms of their size, shape, stability, drug loading and release capacity renders the accuracy-a basic demand for drug administration-much lower than that of the photosensitizer-conjugated targeting biomolecule approach.…”

“…[20,21] Although these two strategies have yielded promising results, they still face challenges. [22] Small molecular-target-based anticancer therapies with specific affinities toward cancer cells, achieved by modulating the aberrant molecular pathways that underlie tumor growth and progression, have shown tremendous success in recent decades. [22] For the latter, the complex structure and low stability of biomacromolecules consistently imposes difficulties in the preparation process, as well as changes-even losses-in biological activities during the modification process.…”

In vitro photodynamic activities of zinc(II) phthalocyanines substituted with pyridine moieties

“…However, tetra-β-substituted phthalocyanine TP2 almost does not show any photocytotoxicity up to 5 µM. The aggregation behavior of photosensitisers has an important effect on their photodynamic activities [3]. Usually, aggregation provides an efficient non-radiative relaxation pathway thereby greatly shortening the excited-state lifetime, and reducing the singlet oxygen quantum yield, as a consequence, the photodynamic activity will greatly reduce, even disappear.…”

pH-responsive metallo-supramolecular nanogel for synergistic chemo-photodynamic therapy

“…Zhang and co-workers synthesized two kinds of zinc(II) phthalocyanine-erlotinib conjugates. In vitro photodynamic activities and selective affinity of these conjugates toward HepG2 cancer cells and A431 tumor tissues were evaluated [21]. Recently, our group had fabricated a kind of dual pH-responsive mesoporous silica nanoparticle (MSN)-based drug delivery system for synergistic chemo-photodynamic therapy, which could respond to the cancer extracellular and intercellular pH stimuli.…”