Synthesis, Tumor Specificity, and Photosensitizing Efficacy of Erlotinib-Conjugated Chlorins and Bacteriochlorins: Identification of a Highly Effective Candidate for Photodynamic Therapy of Cancer.
Ravindra R CherukuJoseph CacaccioFarukh A DurraniWalter A TabaczynskiRamona WatsonKevin SitersJoseph R MissertErin C TracyMykhaylo DukhKhurshid A GuruRichard C KoyaPawel KalinskiHeinz BaumannRavindra K PandeyPublished in: Journal of medicinal chemistry (2021)
Erlotinib was covalently linked to 3-(1'-hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH) and structurally related chlorins and bacteriochlorins at different positions of the tetrapyrrole ring. The functional consequence of each modification was determined by quantifying the uptake and subcellular deposition of the erlotinib conjugates, cellular response to therapeutic light treatment in tissue cultures, and in eliminating of corresponding tumors grown as a xenograft in SCID mice. The experimental human cancer models the established cell lines UMUC3 (bladder), FaDu (hypopharynx), and primary cultures of head and neck tumor cells. The effectiveness of the compounds was compared to that of HPPH. Furthermore, specific functional contribution of the carboxylic acid side group at position 172 and the chiral methyl group at 3(1') to the overall activity of the chimeric compounds was assessed. Among the conjugates investigated, the PS 10 was identified as the most effective candidate for achieving tumor cell-specific accumulation and yielding improved long-term tumor control.
Keyphrases
- photodynamic therapy
- papillary thyroid
- epidermal growth factor receptor
- advanced non small cell lung cancer
- cell therapy
- endothelial cells
- randomized controlled trial
- systematic review
- squamous cell
- ionic liquid
- spinal cord injury
- squamous cell carcinoma
- stem cells
- type diabetes
- mesenchymal stem cells
- insulin resistance
- cancer therapy
- high resolution
- induced pluripotent stem cells
- metabolic syndrome
- fluorescence imaging
- structural basis
- drug delivery
- adipose tissue
- atomic force microscopy