The insufficient blood flow and oxygen supply in solid tumor cause hypoxia, which leads to low sensitivity of tumorous cells and thus causing poor treatment outcome. Here, mesoporous manganese dioxide (mMnO 2 ) with ultrasensitive biodegradability in a tumor microenvironment (TME) is grown on upconversion photodynamic nanoparticles for not only TME-enhanced bioimaging and drug release, but also for relieving tumor hypoxia, thereby markedly improving photodynamic therapy (PDT). In this nanoplatform, mesoporous silica coated upconversion nanoparticles (UCNPs@mSiO 2 ) with covalently loaded chlorin e6 are obtained as near-infrared light mediated PDT agents, and then a mMnO 2 shell is grown via a facile ultrasonic way. Because of its unique mesoporous structure, the obtained nanoplatform postmodified with polyethylene glycol can load the chemotherapeutic drug of doxorubicin (DOX). When used for antitumor application, the mMnO 2 degrades rapidly within the TME, releasing Mn 2+ ions, which couple with trimodal (upconversion luminescence, computed tomography (CT), and magnetic resonance imaging) imaging of UCNPs to perform a selfenhanced imaging. Significantly, the degradation of mMnO 2 shell brings an efficient DOX release, and relieve tumor hypoxia by simultaneously inducing decomposition of tumor endogenous H 2 O 2 and reduction of glutathione, thus achieving a highly potent chemo-photodynamic therapy.

No abstract

NIR light-induced imaging-guided cancer therapy is an encouraging route in the cancer theranostic field. Herein, we describe a novel nanoscale proposal, which is established by covalently implanting core-shell structured upconversion nanoparticles (UCNPs) with nanographene oxide (NGO) by a process utilizing polyethylene glycol (PEG), and consequently loading Chlorin e6 (Ce6) onto the surface of NGO. The acquired NGO-UCNP-Ce6 (NUC) nanocomposites can not only be employed as upconversion luminescence (UCL) imaging probes of cells and whole-body animals with high contrast for diagnosis, but also can generate reactive oxygen species (ROS) under 808 nm light excitation for photodynamic therapy (PDT); over and above, they can swiftly and proficiently translate the 808 nm photon into thermal energy for photothermal therapy (PTT). An extraordinarily enhanced and synchronized therapeutic effect paralleled to the individual PTT or PDT is achieved, rendering extraordinary therapeutic effectiveness for cancer treatment. Consequently, profiting from this inimitable multifunctional nanohybrid, the NUCs synthesized here are encouraging as a cohesive theranostic probe for impending UCL imaging-guided combinatorial PDT/PTT.

Near infrared (NIR) light triggered phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) affords superior outcome in cancer treatment. However, the reactive oxygen species (ROS) generated by NIR-excited upconversion nanostructure is limited by the feeble upconverted light which cannot activate PDT agents efficiently. Here, an IR-808 dye sensitized upconversion nanoparticle (UCNP) with a chlorin e6 (Ce6)-functionalized silica layer is developed for PDT agent. The two booster effectors (dye-sensitization and core-shell enhancement) synergistically amplify the upconversion efficiency, therefore achieving superbright visible emission under low 808 nm light excitation. The markedly amplified red light subsequently triggers the photosensitizer (Ce6) to produce large amount of ROS for efficient PDT. After the silica is endowed with positive surface, these PDT nanoparticles can be easily grafted on MoS nanosheet. As the optimal laser wavelength of UCNPs is consistent with that of MoS nanosheet for PTT, the invented nanoplatform generates both abundant ROS and local hyperthermia upon a single 808 nm laser irradiation. Both the in vitro and in vivo assays validate that the innovated nanostructure presents excellent cancer cell inhibition effectiveness by taking advantages of the synergistic PTT and PDT, simultaneously, posing trimodal (upconversion luminescence/computed tomography (CT)/magnetic resonance imaging (MRI) imaging capability.

Lanthanide-doped photon upconverting nanomaterials are evolving as a new class of imaging contrast agents, offering highly promising prospects in the area of biomedical applications. Owing to their ability to convert long-wavelength near-infrared excitation radiation into shorter-wavelength emissions, these nanomaterials are well suited to yield properties of low imaging background, large anti-Stokes shift, along with high optical penetration depth of NIR light for deep tissue optical imaging or light-activated drug release and therapy. Such materials have potential for significant advantages in analytical applications compared to molecular fluorophores and quantum dots. The use of IR radiation as an excitation source diminishes autofluorescence and scattering of excitation radiation, which leads to a reduction of background in optical experiments. The upconverting nanocrystals show exceptional photostability and are constituted of materials that are not significantly toxic to biological organisms. Excitation at long wavelengths also minimizes damage to biological materials. In this detailed review, various mechanisms operating for the upconversion process, and methods that are utilized to synthesize and decorate upconverting nanoparticles are investigated to elucidate by what means absorption and emission can be tuned. Up-to-date reports concerning cellular internalization, biodistribution, excretion, cytotoxicity and in vivo toxic effects of UCNPs are discussed. Specifically, studies which assessed the relationship between the chemical and physical properties of UCNPs and their biodistribution, excretion, and toxic effects are reviewed in detail. Finally, we also deliberate the challenges of guaranteeing the biosafety of UCNPs in vivo.

No abstract

No abstract

Silica related nanovehicles are being widely studied for bioapplication, while the use in vivo has been restricted due to the biodegradation reluctance. Herein, a facile Mn-doping method was used to endow the upconversion nanoparticles (UCNPs) with a biodegradable shell, simply by transforming mesoporous silica coated UCNPs (UCNPs@mSiO2) to Mn-doped upconversion nanocapsules (Mn-UCNCs). The yolk-structured Mn-UCNCs have huge internal space, which is greatly beneficial for DOX (a chemotherapeutic agent) storage. Furthermore, the Mn-doped nanoshell is responsive to mild reductive and acidic tumor condition, which enables the biodegradation of the silica shell in tumor sites and further accelerates the breakup of Si–O–Si bonds within the silica framework. This tumor-sensitive degradation of the shell not only facilitates DOX release in the tumor location but also allows faster nanoparticle diffusion and deeper tumor penetration, thus realizing efficient particle distribution and improved chemotherapy. Moreover, the biodegradability-enhanced DOX release brings a rapid recovery to the total emission intensity and a drastic decline to the red/green (R/G) ratio, which can be used to sense the drug release extent. The MRI effect caused by Mn release coupled with the inherent MRI/CT/UCL imaging derived from the UCNPs (NaGdF4:Yb,Er@NaGdF4:Yb) under NIR irradiation endow the nanocarrier with superior multiple imaging functions. The high biocompatibility of PEGylated Mn-UCNCs was validated, and the excellent anticancer effectiveness of the DOX loaded nanosystem was also achieved.