Chemically robust fluoroalkyl phthalocyanine–oligonucleotide bioconjugates and their GRP78 oncogene photocleavage activity

Abstract

The first representative of functionalized fluoroalkyl phthalocyanines, F48H7(COOH)PcZn, is reported. The complex generates (1)O2 affording long-lasting photooxidation of an external substrate without self-decomposition. The carboxylic group couples with an antisense oligonucleotide targeting GRP78 oncogenes, resulting in the F48H7PcZn-cancer targeting oligonucleotide (CTO). The bioconjugated fluorophthalocyanine effectively hybridizes complementary GRP78 DNA and mRNA sequences. Piperidine cleavage assays reveal desired photochemical oligonucleotide oxidative degradation for both F48H7PcZn-CTO:DNA and F48H7PcZn-CTO:mRNA hybrids. This new materials strategy could be extended to other functional fluorinated phthalocyanines-antisense oligonucleotide combinations for long-lasting oncogene-targeting photodynamic therapy.

Synthesis, characterization, and biological activity of poly(arginine)-derived cancer-targeting peptides in HepG2 liver cancer cells

“…A trypan blue cell exclusion staining assay confirmed modest levels of cell death at 0.15 mM of peptides. In a dose‐response assay, Pep42‐R 9 ( 10 ) was also found to exhibit 5–10% cancer cell death from 0 to 1.5 mM indicating that the peptides may have utility in the safe and selective administration of oncogene therapeutics .…”

“…The GRP78 receptor is a 78 kDa member of the heat shock family of proteins which functions as an intracellular chaperone by regulating protein folding events in the endoplasmic reticulum [15][16][17]. In cancer, GRP78 is overexpressed and cell surface localized, where it exhibits a variety of signaling pathways that induce cancer initiation, proliferation, and metastatic spread [18][19][20][21]. Moreover, GRP78 has been found on the plasma membrane of a variety of cancer cell types but not in normal tissues, making it a valuable biomarker for cancer-targeted therapy [14][15][16][17][18][19][20][21].…”

“…In cancer, GRP78 is overexpressed and cell surface localized, where it exhibits a variety of signaling pathways that induce cancer initiation, proliferation, and metastatic spread [18][19][20][21]. Moreover, GRP78 has been found on the plasma membrane of a variety of cancer cell types but not in normal tissues, making it a valuable biomarker for cancer-targeted therapy [14][15][16][17][18][19][20][21]. Toward this goal, Pep42 has been effectively conjugated with Taxol, and the pro-apoptotic D-(KLAKLAK) 2 sequence triggering programmed cell death specifically in human melanoma cancer cell lines and in xenograft mouse models [22].…”

Nucleic Acid Bioconjugates in Cancer Detection and Therapy

“…The bioconjugate 40 was shown to effectively hybridize complementary GRP78 DNA and mRNA sequences. In a photo‐oxidation and cleavage assay, the fluorophthalocyanine–AON was found to sensitize degradation of the GRP78 oncogenes at oxidized sites, underscoring its potential in GRP78‐targeting PDT applications …”

Synthesis and Photophysical and Photocatalytic Properties of a Highly Fluorinated and Durable Phthalocyanine–Peptide Bioconjugate for Potential Theranostic Applications

“…Supplementing van der Waals interactions with potential covalent binding capabilities may allow the coupling of fluorophthalocyanines with a biovector that could impart tumor-homing abilities to the resulting bioconjugate. Bioconjugation of MPc’s to tumor-homing ligands, such as oligonucleotides, peptides, and antibodies, can improve the PDT performance. − ZnPc’s, Sonogashira-coupled to RGD and bombesin (Tyr-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH 2 ) peptides, have been reported to exhibit cell uptake and photocytotoxicity by targeting integrin- and gastrin-releasing peptide receptors, respectively, in several tumor cell lines . Trisulfonated ZnPc-bombesin produces phototoxic LD 50 values of <5 J cm –2 in PC3, A549, MDA-MB-23, and EMT-6 cell lines.…”