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<p>The discovery, formulation, and characterization of novel compositions of matter
for aid in the diagnosis and treatment of disease has ever been a compelling force
behind nanomaterials development. In instances of disease originating from oncogenic
mutation, proliferation, and metathesis; cancer has long been a most difficult dysfunction
to diagnosis and treat in virtue of its innate alteration and disregulation of otherwise
well-managed and healthful cellular processes. To date, cancer therapies have relied
largely on highly toxic chemotherapy or radiation treatments, addressing the overarching
problem of individual cellular mutations in a global sense, often deleterious to the
overall health of the patient. Ever-progressing work on nanomaterial-based applications
to either promote cancer diagnosis or implement novel therapeutic means of drug delivery,
activation, or the precisely-targeted destruction of cancer cell lines has been afforded
much attention in the integrated biological and materials science fields. Recent developments
in nanosized laser materials incorporating lanthanide-doped sensitizer and activator
pairs and the development of numerous crystallographic, co-dopant, morphological,
and/or surface-appended optimizations to these materials have given rise to a novel
class of nanomaterials, with unique photophysical properties that have direct import
into light-based activation of chemical processes, triggered non-invasively through
biological tissues, and merging intra-cellularly targetable nanocrystalline compositions
and ex vivo light activation. Upconverting nanocrystals (UCNCs) are one such class
of nanomaterial wherein near-infrared (NIR) light, at the nadir of tissue absorption,
can serve to sequentially or cooperatively excite long-lived lanthanide (Ln3+) 4f
excited states and, through various energy transfer processes coupled between both
the UCNC material composition and its integral Ln3+ dopants, are capable of building
an excited state population capable of emitting in higher frequencies than its incident
NIR excitation.</p><p>In the study of these UCNCs, the prospect of activating intra-cellular
photodynamic processes or drugs of low cellular toxicity, until light activated in
a precisely localized regime (e.g. the nucleus of a cell), has motivated extensive
research into the generation of novel UCNC materials, in multiple compositions and
on multiple size scales to direct the mechanisms of upconversion (UC) to produce high
fluence ultraviolet (UV) photons upon NIR (972 nm) excitation. Continuing optimizations
have yielded a high ytterbium (Yb) sensitizer, cubic α-NaYbF4 UCNC composition,
codoped with a thulium activator, to generate excited state saturated UV transitions,
1I6 → 3F4 (349 nm) and 1D2 → 3H6 (362 nm), and their refinement to afford
dominant UV emissive spectral signatures at low NIR laser excitation. Their photophysical
dynamics are sparsely described in the literature, breaking from both fields of laser
photonics and conventional inorganic nanoscience, and require renewed emphasis to
be afforded in exacting crystallographic, photophysical, and size dependent effect
characterization, heavily directing the structure-function relationships of luminescent
Ln3+ dopants and their host crystal matrices. Requisite in this study is a call for
the optimization of uniform, monodisperse, and reproducible preparations of unique
UCNCs and precise characterization of the properties they display and the origins
thereof.</p><p>Offered herein are the enveloping efforts to more fully understand
the mechanistic processes of UC of both poorly characterized, literature standard
materials, novel UCNCs tuned for enhancement of UC emission in the UV, and the adaptations
to each that ultimately affect their photophysical dynamics. A tandem course of this
research follows from inorganic shelling, passivation methodologies to ameliorate
crystallographic surface defects and UC luminescence quenching sites to overall enhance
the dominant UV emissivity of novel co-doped UCNC. These state-of-the-art UC materials
are: 1) α-NaYbF4: Tm3+, interlaced with gallium, chromium, yttrium, and other
trivalent metal ions, serving to finely modulate UC mechanistic processes and enhance
luminescent properties and 2) sodium co-doped LaF3 and BaLaF4 (0.5%Tm, 20%Yb), displaying
3 and 2 orders of magnitude enhancement of UV emissions due to controlled perturbation
of the local crystal field environment. The Core @ Shell architectural derivatives
of these materials exhibit an eminent departure from classical luminescent fluorophores,
phosphors, or quantum confined luminescent nanomaterials, in both degree of luminescent
flux generation and the complicated mechanistic processes they are derived from.</p><p>To
a great extent, this work attempts to establish testable grounds for comparison of
UCNCs; extending from interrogation of photophysical lifetime measurements, excitation
versus emissive flux power dependence studies, high resolution X-ray photoelectron
spectroscopy (HR-XPS) and power diffraction (HR-XRD) assessments of crystallographic
defects and perturbations on the atomic scale, and the establishment of new metrics
of radiant flux versus absolute quantum yield for use in comparison of UCNCs towards
their applicability in areas of variable or limited excitation flux and the ultimate
utility of discerning hit-to-lead UCNC materials for medical nanodevice compositions.
A salient component affecting these metrics is the direct surface interactions with
respect to solvents, coordinating ligands, and appended functional moieties for enhancement
of UCNCs towards specific applications; largely directed towards cancer biology and
medical study. In a confluence of inquisition of UCNCs and their high energy, UV luminescent
properties, interfacing with the surface presenting effects of solublization and bio-targeting
molecular functionalization; literature standard, β-NaYF4 (2%Er, 20%Yb) UCNCs
have been generated in highly uniform compositions to assess the size-dependent effects
with respect to luminescent quenching surrounding a UCNC surface and functionalization
methodologies have been offered as a proof of concept towards the construction of
an optimized biomolecular targeting nanodevice, with known limits and predictable
interactions, both to NIR excitation light and potential intra-cellular biological
environments.</p><p>The ultimate goal of these explorations is the innovative fusion
of the above concepts into a nanotherapeutic device involving: 1) the generation of
a well-studied and predictable NIR-absorbing and dominant UV-emissive UCNC, with defined
co-dopant optimizations and employing an optimal Core @ Shell architecture, 2) the
requisite surface functionalization needed to afford aqueous solubility and a means
of covalently conjugating targeting molecules of interest, and 3) the ultimate and
equal assessment of such a composite system with respect to possible alternate materials
in the literature and novel UCNCs currently under development. To date, no such convergent
study has been conducted to any degree of reproducibility or certainty of desired
and defined functionality. In this work is described in detail each optimized component
for such a device or potentially one marked by differing, but assessable conditions
for alternate applications. The optimization of a sub-10 nm, dominant UV-emissive
UCNC, the crystallographic and photophysical origins of its UC mechanism under varied
conditions, and the optimal means of their employment (both in terms of establishing
equivalent metrics and utility in cancer nanotherapeutics), assessment, and readdressing
of, as yet undiscovered limits to these materials are presented.</p>
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