Abstract 4051
Background
Pyropheophorbide-a (Pyro) is a highly promising photosensitizer for tumor photodynamic therapy (PDT), while its very limited tumor-accumulation ability seriously restricts its clinically applications. Higher accumulation of photosensitizers are very important for the treatment of deeply seated and larger tumors. Conjugation of Pyro with tumor homing peptide ligands could be a very useful strategy to optimize the physical properties of Pyro. Herein, we reported our studies on the conjugation of Pyro with a cyclic cRGDfK (cRGD) peptide, an integrin binding sequence, with the aim to development a highly tumor specific photosensitizers for PDT application.
Methods
In order to further reduce the non-specific uptake and thus reduce the background distribution of the conjugates in the normal tissues, we opted to add a highly hydrophilic polyethylene glycol (PEG) chain and an extra strongly hydrophilic carboxylic acid group as the linker to avoid the direct connection of strong hydrophobic Pyro macrocycle and cRGD ligand. While hydrophilic modification may affect the PDT activity of photosensitizers via reduction of the membrane attachment. We reported here the synthesis and characterization of these conjugates. Their tumor accumulation ability and photodynamic induced cell killing ability were evaluated through both in vitro cell-base experiment and in vivo distribution and tumor therapy experiments with tumor-bearing mice.
Results
As a result, the synthesized conjugate significantly improved the tumor enrichment and tumor selectivity of Pyro, and abolished the xenograft tumors in the murine model through one time of PDT treatment.
Conclusions
In view of the simple synthesis process and excellent tumor treatment ability, this compound has good clinical application potential.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Tianjin Union Medical Center.
Funding
Nankai University.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5189 - Association between serum HGF levels and neutrophil counts in small cell lung cancer and their impact on survival
Presenter: Laura Moliner
Session: Poster Display session 1
Resources:
Abstract
3539 - Prognostic role of RLF/MYCL1 and circPVT1 in SCLC.
Presenter: Clelia Tiziana Storlazzi
Session: Poster Display session 1
Resources:
Abstract
3438 - High-biologically effective dose radiotherapy improve the survival of small cell lung cancer patients with brain metastases: a propensity-matching analysis
Presenter: Qingyang Zhuang
Session: Poster Display session 1
Resources:
Abstract
3232 - Phase 1 open-label study evaluating the safety, pharmacokinetics, and preliminary efficacy of ABBV-181 and rovalpituzumab tesirine (ROVA-T) in patients with small cell lung cancer
Presenter: Emiliano Calvo
Session: Poster Display session 1
Resources:
Abstract
3633 - Activity of the novel Aurora kinase B inhibitor AZD2811 in biomarker-defined models of small cell lung cancer
Presenter: Carminia Maria Della Corte
Session: Poster Display session 1
Resources:
Abstract
3745 - Multi-level proteomics identifies FABP5 as a primary chemoresistance mediator in extensive-stage small cell lung cancer
Presenter: Yamei Chen
Session: Poster Display session 1
Resources:
Abstract
5049 - CLEPSIDRA trial: a pilot, biomarker-guided study to assess safety, tolerability, dose finding and efficacy of iadademstat in combination with platinum-etoposide in patients with relapsed, extensive-stage small cell lung cancer
Presenter: Alejandro Navarro Mendivil
Session: Poster Display session 1
Resources:
Abstract
5997 - Phased Avelumab combined with chemotherapy as first-line treatment for patients with advanced small-cell lung cancer (SCLC): The PAVE study, a Hellenic Cooperative Oncology Group Study
Presenter: Helena Linardou
Session: Poster Display session 1
Resources:
Abstract
4502 - Tobacco use in lung cáncer (LC) patients (p) in Spain
Presenter: Enric Carcereny Costa
Session: Poster Display session 1
Resources:
Abstract
4369 - Biomarker testing of lung cancer in Spain
Presenter: Delvys Rodriguez Abreu
Session: Poster Display session 1
Resources:
Abstract