Cold-Responsive Hyaluronated Upconversion Nanoplatform for Transdermal Cryo-Photodynamic Cancer Therapy.

Cryotherapy leverages controlled freezing temperature interventions to engender a cascade of tumor-suppressing effects. However, its bottleneck lies in the standalone ineffectiveness. A promising strategy is using nanoparticle therapeutics to augment the efficacy of cryotherapy. Here, a cold-responsive nanoplatform composed of upconversion nanoparticles coated with silica - chlorin e6 - hyaluronic acid (UCNPs@SiO2-Ce6-HA) is designed. This nanoplatform is employed to integrate cryotherapy with photodynamic therapy (PDT) in order to improve skin cancer treatment efficacy in a synergistic manner. The cryotherapy appeared to enhance the upconversion brightness by suppressing the thermal quenching. The low-temperature treatment afforded a 2.45-fold enhancement in the luminescence of UCNPs and a 3.15-fold increase in the photodynamic efficacy of UCNPs@SiO2-Ce6-HA nanoplatforms. Ex vivo tests with porcine skins and the subsequent validation in mouse tumor tissues revealed the effective HA-mediated transdermal delivery of designed nanoplatforms to deep tumor tissues. After transdermal delivery, in vivo photodynamic therapy using the UCNPs@SiO2-Ce6-HA nanoplatforms resulted in the optimized efficacy of 79% in combination with cryotherapy. These findings underscore the Cryo-PDT as a truly promising integrated treatment paradigm and warrant further exploring the synergistic interplay between cryotherapy and PDT with bright upconversion to unlock their full potential in cancer therapy.

Hyaluronate-Black Phosphorus-Upconversion Nanoparticle Complex for Non-invasive Theranosis of Skin Cancer.

Despite the wide investigation on black phosphorus (BP) for biophotonic applications, the finite depth of light penetration has limited further development of BP-based photomedicines. Here, we developed a hyaluronate-BP-upconversion nanoparticle (HA-BP-UCNP) complex for near-infrared (NIR) light-mediated multimodal theranosis of skin cancer with photoacoustic (PA) bioimaging, photodynamic therapy (PDT), and photothermal therapy (PTT). In contrast to the conventional BP-based skin cancer theranosis, the HA-BP-UCNP complex could be non-invasively delivered into the tumor tissue to induce the cancer cell apoptosis upon NIR light irradiation. The PA imaging of BP successfully visualized the non-invasive transdermal delivery of the HA-BP-UCNP complex into the mice skin. HA in the complex facilitated the transdermal delivery of BP into the tumor tissue under the skin. Upon 980 nm NIR light irradiation, the UCNP converted the light to UV-blue light to generate reactive oxygen species by sensitizing BP in the HA-BP-UCNP complex for PDT. Remarkably, 808 nm NIR irradiation with PTT triggered the apoptosis of tumor cells. Taken together, we could confirm the feasibility of the HA-BP-UCNP complex for NIR light-mediated multimodal theranosis of skin cancers.

Upconversion nanomaterials and delivery systems for smart photonic medicines and healthcare devices.

In the past decade, upconversion (UC) nanomaterials have been extensively investigated for the applications to photomedicines with their unique features including biocompatibility, near-infrared (NIR) to visible conversion, photostability, controllable emission bands, and facile multi-functionality. These characteristics of UC nanomaterials enable versatile light delivery for deep tissue biophotonic applications. Among various stimuli-responsive delivery systems, the light-responsive delivery process has been greatly advantageous to develop spatiotemporally controllable on-demand "smart" photonic medicines. UC nanomaterials are classified largely to two groups depending on the photon UC pathway and compositions: inorganic lanthanide-doped UC nanoparticles and organic triplet-triplet annihilation UC (TTA-UC) nanomaterials. Here, we review the current-state-of-art inorganic and organic UC nanomaterials for photo-medicinal applications including photothermal therapy (PTT), photodynamic therapy (PDT), photo-triggered chemo and gene therapy, multimodal immunotherapy, NIR mediated neuromodulations, and photochemical tissue bonding (PTB). We also discuss the future research direction of this field and the challenges for further clinical development.

Multispectral upconversion nanoparticles for near infrared encoding of wearable devices.

Individual recognition technology such as iris recognition and bar coding has been extensively investigated for non-face-to-face authorization. However, there are still strong unmet needs for facile, rapid, and robust individual recognition. Here, we developed multispectral transparent films of upconversion nanoparticles (UCNPs) for near-infrared (NIR) encoding of wearable devices including contact lenses and patch devices. A multispectral UCNP film in a contact lens showed various luminescence colors of patterns under 980 nm NIR light irradiation and each color could be assigned to a specific code by RGB value analysis. The encoded film of UCNPs in the contact lens was successfully decoded by the RGB value analysis with a charge coupled digital (CCD) camera. Furthermore, the UCNP barcode film could be applied in the form of attachable barcode patches onto various substrates like porcine skin and paper currency. Taken together, we could confirm the feasibility of multispectral UCNP transparent films as a facile individual recognition platform for non-face-to-face authorization.

Biocompatible Magnesium Implant Double-Coated with Dexamethasone-Loaded Black Phosphorus and Poly(lactide-co-glycolide).

Magnesium (Mg) and its alloys have presented a paradigm for biodegradability in the field of biomedical devices. However, biodegradation of Mg and its alloys cause the formation of hydrogen gas and basic molecules in the body. Here we developed a surface modification method for Mg implants by double-coating with osteogenic dexamethasone (Dex)-loaded black phosphorus (BP) and poly(lactide-co-glycolide) (PLGA). According to electrochemical and biodegradation tests, the prepared Mg-Dex/BP/PLGA showed remarkably enhanced resistance against corrosion possibly by the neutralization of basic molecules from Mg implants with acidic molecules from BP and PLGA with increasing biodegradation. Scanning electron microscopy, cell proliferation tests, Alizarin Red staining, and alkaline phosphatase activity tests confirmed that MC3T3-E1 cells significantly proliferated and were differentiated on the Mg-Dex/BP/PLGA surface. Taken together, the facile surface modification of Mg implants could be effectively harnessed for protecting the Mg surface from corrosion and inducing the osseointegration of preosteoblasts onto the Mg implant.