Plasmon-Enhanced Photodynamic Cancer Therapy by Upconversion Nanoparticles Conjugated with Au Nanorods

Photodynamic therapy (PDT) based on photosensitizers (PSs) constructed with nanomaterials has been widely applied to treat cancer. This therapy is characterized by an improved PS accumulation in tumor regions. However, challenges, such as short penetration depth of light and low extinction coefficient of PSs, limit PDT applications. In this study, a nanocomposite consisting of NaYF₄:Yb/Er upconversion nanoparticles (UCPs) conjugated with gold nanorods (Au NRs) was developed to improve the therapeutic efficiency of PDT. Methylene blue (MB) was embedded in a silica shell for plasmon-enhanced PDT. UCPs served as a light converter from near-infrared (NIR) to visible light to excite MB to generate reactive oxygen species (ROS). Au NRs could effectively enhance upconversion efficiency and ROS content through a localized surface plasmon resonance (SPR) effect. Silica shell thickness was adjusted to investigate the optimized MB loading amount, ROS production capability, and efficient distance for plasmon-enhanced ROS production. The mechanism of plasmon-enhanced PDT was verified by enhancing UC luminescence intensity through the plasmonic field and by increasing the light-harvesting capability and absorption cross section of the system. This process improved the ROS generation by comparing the exchange of Au NRs to Au nanoparticles with different SPR bands. NIR-triggered nanocomposites of UCP@SiO₂:MB-NRs were significantly confirmed by improving ROS generation and further modifying folic acid (FA) to develop an active component targeting OECM-1 oral cancer cells. Consequently, UCP@SiO₂:MB-NRs-FA could highly produce ROS and undergo efficient PDT in vitro and in vivo. The mechanism of PDT treatment by UCP@SiO₂:MB-NRs-FA was evaluated via the cell apoptosis pathway. The proposed process is a promising strategy to enhance ROS production through plasmonic field enhancement and thus achieve high PDT therapeutic efficacy

Near-Infrared-Activated Fluorescence Resonance Energy Transfer-Based Nanocomposite to Sense MMP2-Overexpressing Oral Cancer Cells

The matrix metalloproteinases (MMPs) are well-known mediators that are activated in tumor progression. MMP2 is a kind of gelatinase in extracellular matrix remodeling and cancer metastasis processes. MMP2 secretion increased in many types of cancer diseases, and its abnormal expression is associated with a poor prognosis. We fabricated a nanocomposite that sensed MMP2 expression by a red and blue light change. This nanocomposite consisted of an upconversion nanoparticle (UCNP), MMP2-sensitive peptide, and CuInS₂/ZnS quantum dot (CIS/ZnS QD). An UCNP is composed of NaYF₄:Tm/Yb@NaYF₄:Nd/Yb, which has multiple emissions at UV/blue-visible wavelengths under 808 nm laser excitation. The conjugated CIS/ZnS QD showed the red-visible fluorescence though the FRET process. The two fluorophores were connected by a MMP2-sensitive peptide to form a novel MMP2 biosensor, named UCNP@p-QD. UCNP@p-QD was highly biocompatible according to cell viability assay. The FRET-based biosensor was employed in the MMP2 determination <i>in vitro</i> and <i>in vivo</i>. Furthermore, it was administrated into the tumor-bearing mouse to check MMP2 expression. UCNP@p-QD could be a promising tool for biological study and biomedical application. In this study, we demonstrated that the CIS/ZnS QD improved the upconversion intensity through a near-infrared-induced FRET process. This nanocomposite has the advantage of light penetration, excellent biocompatibility, and high sensitivity to sense MMP2. The near-infrared-induced composites are a potential inspiration for use in biomedical applications

Evaluations of the Chemical Stability and Cytotoxicity of CuInS₂ and CuInS₂/ZnS Core/Shell Quantum Dots

Recently, CuInS₂ quantum dots (CIS QDs) are extensively applied in biological applications because of their distinctive optical property. These novel ternary semiconductor CIS QDs can be developed into good biomarkers or trackers because they do not contain cadmium, unlike CdTe and CdSe QDs with high risk for cytotoxicity. However, reports on toxicity and effective factors affecting CIS QDs are seldom developed, and in vivo chemical stability has not been clearly investigated. In this study, we focused on the fate, degradation, and exposure time of CIS QDs in Caenorhabditis elegans (C. elegans), which is used as a model organism in biology. Moreover, X-ray absorption near-edge structure (XANES) is used to identify the oxidation state of CIS and CIS/ZnS QDs in various exposure times. The purpose was to use different oxidation states of copper and zinc ions of QDs to achieve chemical stability in C. elegans. CIS and CIS/ZnS QDs were synthesized by hydrothermal method, and QDs were transferred to aqueous solution by coating with <i>O</i>-carboxymethylchitosan (OCMCS). Moreover, intracellular uptake and cell viability tests were estimated as preliminary experiments for in vitro cytotoxicity testing. Our results showed that the supported QD materials can be applied in biological systems. Consequently, we further considered the function of QD materials in C. elegans. The QD materials of coating OCMCS could be successfully delivered to the interior of the C. elegans through the alimentary system in a manner dependent on the exposure time. Most importantly, XANES results revealed that the oxidative state of CIS QDs did not change without an outer layer after treatment for 96 h in C. elegans. Therefore, the extreme chemical stability of CIS QDs may explain the low cytotoxicity in the organism and thus has potential biomedical applications

Near-Infrared Light-Mediated Photodynamic Therapy Nanoplatform by the Electrostatic Assembly of Upconversion Nanoparticles with Graphitic Carbon Nitride Quantum Dots

Photodynamic therapy (PDT) is a promising antitumor treatment that is based on photosensitizers. This therapy kills cancer cells by generating reactive oxygen species (ROS) after irradiation with specific laser wavelengths. Being a potential photosensitizer, graphitic carbon nitride (g-C₃N₄) quantum dots (QDs) are noncytotoxic. Although the use of g-C₃N₄ QDs is challenged by the limited tissue penetration of UV light, g-C₃N₄ QDs display excellent ultraviolet (UV) light-triggered cytotoxicity. The g-C₃N₄ QDs were synthesized using a solid-phase hydrothermal method. The well-distributed hydrophilic g-C₃N₄ can be combined with NaYF₄:Yb³⁺/Tm³⁺ upconversion nanoparticles via the positive ligand poly­(l-lysine) to produce the final nanocomposite, NaYF₄:Yb/Tm-PLL@g-C₃N₄. Upconversion nanoparticles can transfer IR light into UV light and promote g-C₃N₄ to release blue-to-green visible light to generate different images. Moreover, g-C₃N₄ is a promising photosensitizer in PDT because g-C₃N₄ can transfer oxygen into toxic ROS. The singlet oxygen formed by g-C₃N₄ displays great potential for use in the treatment of cancer

Single 808 nm Laser Treatment Comprising Photothermal and Photodynamic Therapies by Using Gold Nanorods Hybrid Upconversion Particles

Light therapy has become the subject of research on cancer treatment because of its selectivity, low invasive damage, and side effects. Photothermal therapy (PTT) and photodynamic therapy (PDT) are prevalent treatments used to induce cancer cell apoptosis by generating heat and reactive oxygen species (ROS). In this study, mesoporous silica shell-coated gold nanorods (AuNR@mS) are synthesized by seed crystal growth method. AuNR@mS are assembled into nanocomposites through electrostatic adsorption with lanthanide-doped upconversion nanoparticles (UCNP). When controlling the aspect ratio of gold nanorods (AuNRs), the surface plasmon resonance peaks of the short-axis and the long-axis match the maximum absorption cross section at 520 and 660 nm of the fluorescence light released by the UCNPs. The converted fluorescence stimulates AuNRs to generate heat through energy transfer. ROS production is induced by loading the photosensitizer Merocyanine 540 (MC540) in the mesoporous silica layer and is further enhanced through the surface plasma resonance effect of the AuNRs. This novel nanoplatform combines PTT and PDT in a single 808 nm near-infrared synergistic light therapy