Advances in nanomedicine enables the development of multifunctional nanoparticle platforms with both diagnostic and therapeutic capabilities. Such platforms allow in vivo tracking of the therapeutic carriers and imaging of tumor response. In this study, we aimed to develop a novel multifunctional targeted nanoparticles for combined cancer imaging and chemoradiotherapy.
Advances in nanomedicine enables the development of multifunctional nanoparticle platforms with both diagnostic and therapeutic capabilities. Such platforms allow in vivo tracking of the therapeutic carriers and imaging of tumor response. In this study, we hypothesized that by adding a chelator/radioisotope component to existing nanoparticle platforms, we can formulate a novel multifunctional nanoparticle that combines nuclear imaging and therapy. Furthermore, nanoparticles that can deliver both chemotherapy and radiotherapy would be especially advantageous as concurrent chemoradiotherapy has emerged as the standard treatment for many cancers. Materials/Methods: A novel targeted polymer‐lipid nanoparticle platform was synthesized by nanoprecipitation method. The resulting nanoparticles have a hydrophobic polymeric core covered by a self‐assembled monolayer (SAM) of lipid and lipid‐PEG and lipid‐chelator. The PLGA core can encapsulate chemotherapeutics, and the DMPE‐DTPA can be used to chelate metal radioisotopes. The outer‐most layer of PEG gives the nanoparticles antibiofouling properties and the DSPE‐PEG‐aptamer provides the targeting function. Results: These polymer‐lipid nanoparticles have hydrodynamic diameter of 70+/‐5 nm, zeta potential of ‐40+/‐5 mV. The seven‐day release profile of docetaxel showed a first‐order release kinetic. Using 111In as the radioisotope, we showed the nanoparticles’ chelation efficiency was 99+/‐0.5%. The seven‐day chelate stability study showed no release of the chelate in the first 36 hours, and approximately a 50% release after 120 hours. As proof of principle, we used prostate cancer as a model and conjugated the A10 RNA aptamer that binds the prostate specific membrane antigen (PSMA) to the nanoparticles. We demonstrated the targeted uptake of these nanoparticles using LNCaP (PSMA+) and PC3 (PSMA‐) prostate cancer cells. Using 90Y, we also demonstrated the efficacy of concurrent chemoradiotherapy nanoparticles is superior than either chemotherapy nanoparticles or radiotherapy nanoparticles. Using 111In, We were able to study the biodistribution of the particles and track the particles using SPECT‐CT imaging in vivo. Conclusions: We have developed a novel targeted nanoparticle platform that can carry both chemotherapeutics and metal radioisotopes, making imaging as well as nanoparticle delivery of concurrent chemoradiotherapy possible.
Author Disclosure: A.Z. Wang, None; A. Guimaraes, None; L. Zhang, None; F. Gu, None; R. Langer, None; R. Weissleder, None; O.C. Farokhzad, None.