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
3336 - Survival outcome of non-small cell lung cancer (NSCLC) patients: Comparing results between the database of the Comprehensive Cancer Center Zürich (CCCZ) and the Epidemiological Cancer Registry Zurich and Zug (KKR)
Presenter: Rolf A. Stahel
Session: Poster Display session 1
Resources:
Abstract
2204 - NORA trial (GECP 15/02): Updated results of the Spanish Lung Cancer Group (SLCG) phase II trial of concurrent chemo-radiotherapy (CT-RT) with cisplatin (P) plus metronomic oral vinorelbine (mOV) for unresectable locally advanced non-small cell lung cancer (LA-NSCLC)
Presenter: María Guirado
Session: Poster Display session 1
Resources:
Abstract
1446 - A nomogram to predict outcomes of lung cancer patients after pneumonectomy based on 47 indicators set by principle component analysis
Presenter: Bo Cheng
Session: Poster Display session 1
Resources:
Abstract
1788 - Prognostic and predictive value of 18F-PET/CT on the response to treatment in locally advanced non-small cell lung cancer (NSCLC)
Presenter: Cristina Alfaro Autor
Session: Poster Display session 1
Resources:
Abstract
2299 - Comparison of three different chemotherapy regimens for concomitant chemoradiotherapy in locally advanced non small cell lung cancer
Presenter: Abdurrahman Işıkdoğan
Session: Poster Display session 1
Resources:
Abstract
4211 - Predicting the first failure pattern in patients with inoperable local advanced non-small cell lung cancer (LA-NSCLC) receiving definitive chemoradiotherapy: Establishment and internal validation of a nomogram based on the clinicopathological factors
Presenter: Xueru Zhu
Session: Poster Display session 1
Resources:
Abstract
1550 - Prognostic impact of neutrophil-to-lymphocyte ratio (NLR) pre and post chemoradiotherapy (CRT) in stage III non-small cell lung cancer (NSCLC)
Presenter: Vicente Palomar Abril
Session: Poster Display session 1
Resources:
Abstract
2345 - Meta-analysis evaluating neutropenia incidence with EGFR inhibitors and chemotherapy in patients with NSCLC
Presenter: Bernardo Rapoport
Session: Poster Display session 1
Resources:
Abstract
3747 - Effector CD4+ T-cell induction by thoracic radiotherapy for patients with NSCLC
Presenter: Yu Miura
Session: Poster Display session 1
Resources:
Abstract
3317 - Circulating tumor DNA (ctDNA) analysis in patients (pts) with non-small cell lung cancer (NSCLC) treated with telisotuzumab vedotin (teliso-v), an antibody-drug conjugate targeting c-Met
Presenter: Rebecca Heist
Session: Poster Display session 1
Resources:
Abstract