A tissue factor-cascade-targeted strategy to tumor vasculature: a combination of EGFP-EGF1 conjugation nanoparticles with photodynamic therapy

Abstract

Tumor requires tumor vasculature to supply oxygen and nutrients so as to support its continued growth, as well as provide a main route for metastatic spread. In this study, a TF-cascade-targeted strategy aiming to disrupt tumor blood vessels was developed by combination of TF-targeted HMME-loaded drug delivery system and PDT. PDT is a promising new modality in the treatment of cancers, which employs the interaction between a tumor-localizing photosensitizer and light of an appropriate wavelength to bring about ROS-induced cell death. In vitro results showed that protein EGFP-EGF1modification could significantly contribute to the uptake of nanoparticles by TF over-expressed BCECs. In vivo multispectral fluorescent imaging, the EGFP-EGF1 conjugated nanoparticles showed significantly higher accumulation in tumor tissues than non-conjugated ones. Tumor tissue slides further presented that EGFP-EGF1 conjugated nanoparticles showed significantly higher accumulation in tumor vasculature than non-conjugated ones. In vitro study demonstrated that PDT increased TF expression of BCECs. In vivo imaging, ex vivo imaging and tumor tissue slides showed that PDT further contribute EGFP-EGF1-NP accumulation in tumor. These promising results indicated that PDT enhanced EGFP-EGF1modified PEG-PLGA nanoparticle accumulation in tumor vaculature. Considering that EGFP-EGF1 conjugation enhanced nanoparticles uptake by TF over-expressed endothelium and PDT increased endothelium TF expression. We conclude that PDT triggered a TF cascade targeted effect. A combination of both EGFP-EGF1 modification and PDT provided a positive feed-back target effect to tumor vessels and might have a great potential for tumor therapy.

Tissue Factor-Targeted “O2-Evolving” Nanoparticles for Photodynamic Therapy in Malignant Lymphoma

“…Furthermore, nanoparticles exhibited excellent stabilities in PBS, RPMI-1640, and 10% FBS without significant aggregation (data not shown). The favorable stability of nanoparticles was demonstrated similar as previously reported (12). Concentrations of HMME, coumarin-6, or Dir in nanoparticles were determined based on their respective absorbance spectra in acetonitrile.…”

“…In previous studies, we prepared a TF-targeted drug delivery system successfully: EGFP-EGF1-NPs-loaded HMME. The system, composed of a factor VII-derived EGFP-EGF1 fusion protein and PEG-PLGA nanoparticle-loaded hematoporphyrin monomethyl ether (HMME), combined with PDT to exhibit efficient TF-cascade-targeting ability in vitro and in vivo (12).…”

Possible importance of Cannabis sativa L. in regulation of insulin and IL-6R/MAO-A in cancer cell progression and migration of breast cancer patients with diabetes

“…12 The growth of breast cancer cells is under the direct regulation of hormones, growth factors, chemokines and their receptors. 13 Both hyperinsulinemia and cancer are extremely prevalent pathophysiological conditions associated with major morbidity and mortality worldwide.…”

Strategies for optimizing the delivery to tumors of macrocyclic photosensitizers used in photodynamic therapy (PDT)

“…PLGA-based nanosystems loaded with 5-aminolevulinic acid (5-ALA) or Protoporphyrin IX have been extensively studied for dermatological applications of PDT [114,115] while the PEGylated version of PLGA NPs have been proposed for the delivery of different PSs to non-dermatological cancers [116][117][118]. Double coated polymeric NPs (dcNPs) having a PLGA core entrapping the lipophilic chemotherapeutic docetaxel (DTX) and decorated with a positively charged layer of polyethyleneimine (PEI) entrapping via electrostatic interaction the negatively charged tetrasodium-mesotetra(4-sulfonatophenyl)porphyrin (TPPS 4 ) and hyaluronic acid (HA), were proposed for chemo/photo-therapy of cancer [119].…”