Theranostic Designed Near-Infrared Fluorescent Poly (Lactic-co-Glycolic Acid) Nanoparticles and Preliminary Studies with Functionalized VEGF-Nanoparticles

Abstract

Poly-lactic-co-glycolic acid nanoparticles (PLGA-NPs) were approved by the Food and Drug Administration (FDA) for drug delivery in cancer. The enhanced permeability and retention (EPR) effect drives their accumulation minimizing the side effects of chemotherapeutics. Our aim was to develop a new theranostic tool for cancer diagnosis and therapy based on PLGA-NPs and to evaluate the added value of vascular endothelial growth factor (VEGF) for enhanced tumor targeting. In vitro and in vivo properties of PLGA-NPs were tested and compared with VEGF-PLGA-NPs. Dynamic light scattering (DLS) was performed to evaluate the particle size, polydispersity index (PDI), and zeta potential of both preparations. Spectroscopy was used to confirm the absorption spectra in the near-infrared (NIR). In vivo, in BALB/c mice bearing a syngeneic tumor in the right thigh, intravenously injected PLGA-NPs showed a high target-to-muscle ratio (4.2 T/M at 24 h post-injection) that increased over time, with a maximum uptake at 72 h and a retention of the NPs up to 240 h. VEGF-PLGA-NPs accumulated in tumors 1.75 times more than PLGA-NPs with a tumor-to-muscle ratio of 7.90 ± 1.61 (versus 4.49 ± 0.54 of PLGA-NPs). Our study highlights the tumor-targeting potential of PLGA-NPs for diagnostic and therapeutic applications. Such NPs can be conjugated with proteins such as VEGF to increase accumulation in tumor lesions.

Synthesis and Biodistribution of 99mTc-Labeled PLGA Nanoparticles by Microfluidic Technique

“…Despite the wide use of PLGA-NPs as delivery drug system, the knowledge of a reproducible incorporation of imaging agents into PLGA-NPs is yet to be explored. In our previous study, we demonstrated how fluorescent PLGA-NPs were able to passively accumulate in a syngeneic tumor model of sarcoma, with maximum uptake at 72 h [22]. Then, the possibility to combine diagnostic agents with therapeutics molecules in NPs, makes them a promising theranostic tool.…”

Localized Therapeutic Approaches Based on Micro/Nanofibers for Cancer Treatment

“…In the study by Varani et al, specific PLGA-NPs were chosen and modified with a NIR fluorochrome, enabling fluorescence to penetrate deeper into tissues. It is possible to observe in Figure 13 how the particles acted as both a drug carrier and an imaging agent [ 96 ]. A similar approach was taken by Park et al, where PCL fibers were loaded with surface openings containing biocompatible photothermal agent.…”

“…On the other hand, the limited light penetration can be overcome through the use of radioactive isotopes, including Copper-64 for positron emission tomography (PET) or Technetium-99m for gamma-camera imaging. Functionalizing with targeting molecules, such as VEGF, may mitigate the serious problem of liver and kidney radiotoxicity posed by the use of radioisotopes, particularly alpha or beta emitters [ 96 ].…”

“… The mouse with a subcutaneous syngeneic tumor was imaged using whole-body optical imaging at various time points (2, 24, 48, 72, 96, 168, and 240 h) after the local administration of 500 µg of fluorescent PLGA-NPs subcutaneously. Reprinted/adapted with permission from Ref [ 96 ]. 2020, Journal of Clinical Medicine.…”

PLGA-Based Nanomedicine: History of Advancement and Development in Clinical Applications of Multiple Diseases

“…In another study, the PLGA-NPs were loaded with a recombinant human VEGF-A165 (the vascular endothelial growth factor, rhVEGF) analog via the 1-Ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) covalent coupling method as a new theranostic technology for tumor diagnosis and therapy by Varani et al as shown in Figure 8. Mice that were injected with VEGF-PLGA-NPs represented elevated tumor uptake and higher target-to-muscle (T/M) ratio in comparison with PLGA-NPs, where the tumor uptake and T/M ratio of VEGF-PLGA-NPs were 39.83 ± 7.17 and 7.90 1.61, while for PLGA-NPs they were 29.95 ± 1.92 and 4.49 0.54, respectively [101]. Figure (A-C) is reproduced from [101] and Figure (D,E) are adapted from [96] with copyright permission.…”