GX1-conjugated poly(lactic acid) nanoparticles encapsulating Endostar for improved in vivo anticolorectal cancer treatment

Abstract

Tumor angiogenesis plays a key role in tumor growth and metastasis; thus, targeting tumor-associated angiogenesis is an important goal in cancer therapy. However, the efficient delivery of drugs to tumors remains a key issue in antiangiogenesis therapy. GX1, a peptide identified by phage-display technology, is a novel tumor vasculature endothelium-specific ligand and possesses great potential as a targeted vector and antiangiogenic agent in the diagnosis and treatment of human cancers. Endostar, a novel recombinant human endostatin, has been shown to inhibit tumor angiogenesis. In this study, we developed a theranostic agent composed of GX1-conjugated poly(lactic acid) nanoparticles encapsulating Endostar (GPENs) and labeled with the near-infrared dye IRDye 800CW to improve colorectal tumor targeting and treatment efficacy in vivo. The in vivo fluorescence molecular imaging data showed that GPENs (IRDye 800CW) more specifically targeted tumors than free IRDye 800CW in colorectal tumor-bearing mice. Moreover, the antitumor efficacy was evaluated by bioluminescence imaging and immunohistology, revealing that GPENs possessed improved antitumor efficacy on subcutaneous colorectal xenografts compared to other treatment groups. Thus, our study showed that GPENs, a novel GX1 peptide guided form of nanoscale Endostar, can be used as a theranostic agent to facilitate more efficient targeted therapy and enable real-time monitoring of therapeutic efficacy in vivo.

A Tumor-Specific Tissue-Penetrating Peptide Enhances the Efficacy of Chemotherapy Drugs in Gastric Cancer

“… 15 Recently, several tumor-specific CPPs have also been developed, such as Pep42 (CTVALPGGYVRVC) for melanomas, NRG (Asn-Gln-Arg) and cRGD [Arg-Gly-Asp-D-Phe-(NMeVal)] for angiogenic blood vessels, and iRGD (CRGDK/RGPD/EC) for various tumors (e.g., prostate cancer, breast cancer, and pancreatic adenocarcinomas). 4 16 17 18 19 20 21 Peptide iRGD could specifically bind to αv integrin in tumor tissue, and then cleaved by protease and exposed to a motif (R/K/XXR/K) for binding to NRP-1, which could mediate penetration into tissues and cells. 3 Conjugation to iRGD significantly improved the sensitivity of tumor-imaging agents and enhanced the activity of antitumor drugs.…”

“…Many researchers have attempted to conjugate anticancer drugs to some tumor-homing molecules [e.g., GX1-rmhTNFα, GX1-conjugated poly (lactic acid) nanoparticles], and these efforts have resulted in more effective antitumor activity than antitumor drugs alone in GC. 7 21 …”

A Novel DNA Aptamer for Dual Targeting of Polymorphonuclear Myeloid-derived Suppressor Cells and Tumor Cells

“…Animals were euthanized 4 h or 8 h post-injection, and major organs and bone samples were collected and visualized with the IVIS-200 imaging system. The signal-to-noise ratio (SNR) was obtained as previously described 41 using the following equation: SNR = η A / η B , where η A and η B are the total radiant efficiency of organs from aptamer-injected and control mice, respectively. Tumor samples were frozen and processed for confocal fluorescence microscopy to detect Cy5-labeled aptamers.…”

Mini-review: fluorescence imaging in cancer cells using dye-doped nanoparticles

“…It should also be noted that functionalized PLA nanoparticles accumulated better and resulted in a higher fluorescence signal than free fluorophore, IRdye 800CW, alone. 194 It was found that the BODIPY fluorophores synthesized by Kim and colleagues could be successfully encapsulated in silica (SiO 2 ) nanoparticles. Then the surface of the silica nanoparticles could be modified to have an arginineglycine-aspartic (RGD) peptide that would selectively target α v β 3 integrin, which lead to enhanced fluorescence imaging with higher signal to background ratios when compared to the free fluorophores alone.…”