Vehicle-Free Nanotheranostic Self-Assembled from Clinically Approved Dyes for Cancer Fluorescence Imaging and Photothermal/Photodynamic Combinational Therapy

Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted growing attention as a noninvasive option for cancer treatment. At present, researchers have developed various “all-in-one” nanoplatforms for cancer imaging and PTT/PDT combinational therapy. However, the complex structure, tedious preparation procedures, overuse of extra carriers and severe side effects hinder their biomedical applications. In this work, we reported a nanoplatform (designated as ICG-MB) self-assembly from two different FDA-approved dyes of indocyanine green (ICG) and methylene blue (MB) without any additional excipients for cancer fluorescence imaging and combinational PTT/PDT. ICG-MB was found to exhibit good dispersion in the aqueous phase and improve the photostability and cellular uptake of free ICG and MB, thus exhibiting enhanced photothermal conversion and singlet oxygen (1O2) generation abilities to robustly ablate cancer cells under 808 nm and 670 nm laser irradiation. After intravenous injection, ICG-MB effectively accumulated at tumor sites with a near-infrared (NIR) fluorescence signal, which helped to delineate the targeted area for NIR laser-triggered phototoxicity. As a consequence, ICG-MB displayed a combinational PTT/PDT effect to potently inhibit tumor growth without causing any system toxicities in vivo. In conclusion, this minimalist, effective and biocompatible nanotheranostic would provide a promising candidate for cancer phototherapy based on current available dyes in clinic

Natural killer cells modified with a Gpc3 aptamer enhance adoptive immunotherapy for hepatocellular carcinoma

Abstract Introduction Natural killer cells can attack cancer cells without prior sensitization, but their clinical benefit is limited owing to their poor selectivity that is caused by the lack of specific receptors to target tumor cells. In this study, we aimed to endow NK cells with the ability to specifically target glypican-3+ tumor cells without producing cell damage or genetic alterations, and further evaluated their therapeutic efficiency. Methods NK cells were modified with a Gpc3 DNA aptamer on the cell surface via metabolic glycoengineering to endow NK cells with specific targeting ability. Then, the G-NK cells were evaluated for their specific targeting properties, cytotoxicity and secretion of cytokines in vitro. Finally, we investigated the therapeutic efficiency of G-NK cells against glypican-3+ tumor cells in vivo. Results Compared with NK cells modified with a random aptamer mutation and unmodified NK cells, G-NK cells induced significant apoptosis/necrosis of GPC3+ tumor cells and secreted cytokines to preserve the intense cytotoxic activities. Moreover, G-NK cells significantly suppressed tumor growth in HepG2 tumor-bearing mice due to the enhanced enrichment of G-NK cells at the tumor site. Conclusions The proposed strategy endows NK cells with a tumor-specific targeting ability to enhance adoptive therapeutic efficiency in GPC3+ hepatocellular carcinoma

Nile Red Derivative-Modified Nanostructure for Upconversion Luminescence Sensing and Intracellular Detection of Fe³⁺ and MR Imaging

Iron ion (Fe³⁺) which is the physiologically most abundant and versatile transition metal in biological systems, has been closely related to many certain cancers, metabolism, and dysfunction of organs, such as the liver, heart, and pancreas. In this Research Article, a novel Nile red derivative (NRD) fluorescent probe was synthesized and, in conjunction with polymer-modified core–shell upconversion nanoparticles (UCNPs), demonstrated in the detection of Fe³⁺ ion with high sensitivity and selectivity. The core–shell UCNPs were surface modified using a synthesized PEGylated amphiphilic polymer (C₁₈PMH-mPEG), and the resulting mPEG modified core–shell UCNPs (mPEG-UCNPs) show good water solubility. The overall Fe³⁺-responsive upconversion luminescence nanostructure was fabricated by linking the NRD to the mPEG-UCNPs, denoted as mPEG-UCNPs-NRD. In the nanostructure, the core–shell UCNPs, NaYF₄:Yb,Er,Tm@NaGdF₄, serve as the energy donor while the Fe³⁺-responsive NRD as the energy acceptor, which leads to efficient luminescence resonance energy transfer (LRET). The mPEG-UCNPs-NRD nanostructure shows high selectivity and sensitivity for detecting Fe³⁺ in water. In addition, benefited from the good biocompatibility, the nanostructure was successfully applied for detecting Fe³⁺ in living cells based on upconversion luminescence (UCL) from the UCNPs. Furthermore, the doped Gd³⁺ ion in the UCNPs endows the mPEG-UCNPs-NRD nanostructure with effective <i>T</i>₁ signal enhancement, making it a potential magnetic resonance imaging (MRI) contrast agent. This work demonstrates a simple yet powerful strategy to combine metal ion sensing with multimodal bioimaging based on upconversion luminescence for biomedical applications

Gadolinium-doped hollow CeO2-ZrO2 nanoplatform as multifunctional MRI/CT dual-modal imaging agent and drug delivery vehicle

Developing multifunctional nanoparticle-based theranostic platform for cancer diagnosis and treatment is highly desirable, however, most of the present theranostic platforms are fabricated via complicated structure/composition design and time-consuming synthesis procedures. Herein, the multifunctional Gd/CeO2-ZrO2/DOX-PEG nanoplatform with single nano-structure was fabricated through a facile route, which possessed MR/CT dual-model imaging and chemotherapy ability. The nanoplatform not only exhibited well-defined shapes, tunable compositions and narrow size distributions, but also presented a well anti-cancer effect and MR/CT imaging ability. Therefore, the Gd/CeO2-ZrO2/DOX-PEG nanoplatform could be applied for chemotherapy as well as dual-model MR/CT imaging

Luminescent and Transparent Nanopaper Based on Rare-Earth Up-Converting Nanoparticle Grafted Nanofibrillated Cellulose Derived from Garlic Skin

Highly flexible, transparent, and luminescent nanofibrillated cellulose (NFC) nanopaper with heterogeneous network, functionalized by rare-earth up-converting luminescent nanoparticles (UCNPs), was rapidly synthesized by using a moderate pressure extrusion paper–making process. NFC was successfully prepared from garlic skin using an efficient extraction approach combined with high frequency ultrasonication and high pressure homogenization after removing the noncellulosic components. An efficient epoxidation treatment was carried out to enhance the activity of the UCNPs (NaYF₄:Yb,Er) with oleic acid ligand capped on the surface. The UCNPs after epoxidation then reacted with NFC in aqueous medium to form UCNP-grafted NFC nanocomposite (NFC–UCNP) suspensions at ambient temperature. Through the paper-making process, the assembled fluorescent NFC–UCNP hybrid nanopaper exhibits excellent properties, including high transparency, strong up−conversion luminescence, and good flexibility. The obtained hybrid nanopaper was characterized by transmission electron microscopy (TEM), atomic force microscope (AFM), Fourier transform infrared spectroscopy (FTIR), field emission-scanning electron microscope (FE-SEM), up−conversion luminescence (UCL) spectrum, and ultraviolet and visible (UV–vis) spectrophotometer. The experimental results demonstrate that the UCNPs have been successfully grafted to the NFC matrix with heterogeneous network. And the superiorly optical transparent and luminescent properties of the nanopaper mainly depend on the ratio of UCNPs to NFC. Of importance here is that, NFC and UCNPs afford the nanopaper a prospective candidate for multimodal anti-counterfeiting, sensors, and ion probes applications

Gadolinium-doped hollow CeO₂-ZrO₂ nanoplatform as multifunctional MRI/CT dual-modal imaging agent and drug delivery vehicle

<p>Developing multifunctional nanoparticle-based theranostic platform for cancer diagnosis and treatment is highly desirable, however, most of the present theranostic platforms are fabricated via complicated structure/composition design and time-consuming synthesis procedures. Herein, the multifunctional Gd/CeO₂-ZrO₂/DOX-PEG nanoplatform with single nano-structure was fabricated through a facile route, which possessed MR/CT dual-model imaging and chemotherapy ability. The nanoplatform not only exhibited well-defined shapes, tunable compositions and narrow size distributions, but also presented a well anti-cancer effect and MR/CT imaging ability. Therefore, the Gd/CeO₂-ZrO₂/DOX-PEG nanoplatform could be applied for chemotherapy as well as dual-model MR/CT imaging.</p