Surface-Modified Shortwave-Infrared-Emitting Nanophotonic Reporters for Gene-Therapy Applications

Abstract

Gene therapy is emerging as the next generation of therapeutic modality with United States Food and Drug Administration approved gene-engineered therapy for cancer and a rare eye-related disorder, but the challenge of real-time monitoring of on-target therapy response remains. In this study, we have designed a theranostic nanoparticle composed of shortwave-infrared-emitting rare-earth-doped nanoparticles (RENPs) capable of delivering genetic cargo and of real-time response monitoring. We showed that the cationic coating of RENPs with branched polyethylenimine (PEI) does not have a significant impact on cellular toxicity, which can be further reduced by selectively modifying the surface characteristics of the PEI coating using counter-ions and expanding their potential applications in photothermal therapy. We showed the tolerability and clearance of a bolus dose of RENPs@PEI in mice up to 7 days after particle injection in addition to the RENPs@PEI ability to distinctively discern lung tumor lesions in a breast cancer mouse model with an excellent signal-to-noise ratio. We also showed the availability of amine functional groups in the collapsed PEI chain conformation on RENPs, which facilitates the loading of genetic cargo that hybridizes with target gene in an in vitro cancer model. The real-time monitoring and delivery of gene therapy at on-target sites will enable the success of an increased number of gene- and cell-therapy products in clinical trials.

RETRACTED ARTICLE: Injectable hydrogel encapsulating Cu2MnS2 nanoplates for photothermal therapy against breast cancer

“…In the past few years, the world has witnessed many new methods in treating cancers [ 1 – 10 ], such as monoclonal antibodies, gene therapy [ 4 , 10 ], photodynamic therapy (PDT), sonodynamic therapy, photothermal therapy (PTT) [ 8 ]. However, cancer therapy is still a big challenge, with the mean survival length of cancer patients only several years.…”

Engineering the Infrared Luminescence and Photothermal Properties of Double-Shelled Rare-Earth-Doped Nanoparticles for Biomedical Applications

“…Based on a previous detailed study of the impregnation process, the functional PEI coating was estimated to be ∼1 nm. 24 The scanning electron microscope (SEM) images show that the as-prepared RENPs exhibited a mostly spherical morphology with the uniform size of approximately 25−26 nm (see Figure 1 and Figure S1). Since the organic shell thicknesses were identical, the particle sizes for the Er-OS and Yb-OS particles were similar, although different amounts of Er and Yb were impregnated within the PEI coating.…”

“…The poorer suspension stability was likely due to the reduced surface charges leading to reduction in particle repulsion and increased particle agglomeration. 24 Further examination of the results for the functional outermost shell enriched with the emitting Er ion (activator ion) revealed additional details regarding the Yb core −Er core , Er core −Er core , and Er shell −Er shell energy-transfer interactions within the Er-IOS and Er-OS particles. Given the presence of a ∼2 nm undoped NaYF 4 layer, energy transfer between the Ln core (Yb or Er) and Er shell are not likely, since the typical optimal interionic separation distance for energy transfer is ≤1.5 nm.…”

Engineering Tumor-Targeting Nanoparticles as Vehicles for Precision Nanomedicine

“…These offer superior detection sensitivity and the capability of multispectral in vivo SWIR imaging. ReANCs have been used to detect emerging and disseminated tumors in melanoma, breast and ovarian cancer mouse models [89–91,157–159].…”