Developing a multifunctional nanocomposite using albumin-encapsulated rare-earth doped nanoparticles for tumor targeting

Optically guided imaging of diseases and surgical procedures is challenged by the lack of photoluminescent probes that can be sensitively detected within living tissues and tracked in real-time. The use of visible light for the detection of conventional probes suffers from poor tissue penetration and non-specific fluorescence. Emerging probes excited using near infrared light (NIR) reduce undesired tissue absorbance, however light scattering resulting from the complex heterogeneity of biological tissues limits the penetration depth of light propagation. Optical probes that emit over a new window of electromagnetic radiation in the short wavelength infrared (SWIR) region can significantly improve in vivo imaging sensitivity compared to NIR. However, current SWIR-detectable probes lack the optical tunability and biocompatibility requisite for biological implantation in vivo. This doctoral dissertation is focused on investigating albumin-derived, biologically interactive nanoparticles as a platform system that can be designed with distinct multifunctional properties, particularly, SWIR imaging and the delivery of therapeutic cargo. The bulk of the thesis is focused on conceptualizing and developing a new class of SWIR-detectable nanomaterials for targeted imaging of cancerous tissues. Conventionally fabricated rare-earth doped nanoprobes (REs) are weakly bioavailable, lack functional surface groups for tissue targeting and exhibit potential cytotoxicity. A major research effort of this thesis was to develop albumin nanoshells around rare-earth nanoprobes for establishing highly biocompatible and biologically targetable RE nanocomposites with controlled sizes and pharmacodynamic behaviors. This study also produced the first evidence reported to date of multi-spectral, real-time SWIR imaging at anatomical resolution in vivo and demonstrated the prospects of REs for targeted molecular imaging. The albumin-encapsulated, inorganic-organic nanocomposite of REs showed enhanced SWIR signal intensity in diseased tissue through accumulation of REs at tumor sites and extended the in vivo retention of REs. Further modifications were made to the albumin coating to create a multifunctional nanoparticle with tumor-penetrating and therapeutic delivery properties for both imaging and drug delivery applications. The cumulative findings of this thesis lay the groundwork for the design of new biomedical probes and imaging methods that have the potential to significantly advance surveillance of a range of diseases with complex molecular etiologies, from cancers to heart disease.Ph. D.Includes bibliographical referencesIncludes vitaby Dominik Jan Naczynsk