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The aim of this study was to develop multifunctional poly lactide-co-glycolide (PLGA) nanoparticles with the ability to simultaneously deliver indocyanine green (ICG) and docetaxel (DTX) to the brain by surface decoration with the brain-targeting peptide angiopep-2 to achieve combined chemo-phototherapy for glioma under near-infrared (NIR) imaging. ICG was selected as a near-infrared imaging and phototherapy agent and DTX was employed as a chemotherapeutic agent. ICG and DTX were simultaneously incorporated into PLGA nanoparticles with higher stability. These nanoparticles were further decorated with angiopep-2 via the outer maleimide group of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000]-maleinimide incorporated in the nanoparticles. The NIR image-guided chemo-phototherapy of the angiopep-2 modified PLGA/DTX/ICG nanoparticles (ANG/PLGA/DTX/ICG NPs) not only highly induced U87MG cell death in vitro, but also efficiently prolonged the life span of the brain orthotopic U87MG glioma xenograft-bearing mice in vivo. Thus, this study suggests that ANG/PLGA/DTX/ICG NPs have the potential for combinatorial chemotherapy and phototherapy for glioma.

It is highly desirable to develop smart nanocarriers with stimuli-responsive drug-releasing and diagnostic-imaging functions for cancer theranostics. Herein, we develop a reduction and pH dual-responsive tumor theranostic platform based on degradable manganese dioxide (MnO2) nanosheets. The MnO2 nanosheets with a size of 20-60 nm were first synthesized and modified with (3-Aminopropyl) trimethoxysilane (APTMS) to get amine-functionalized MnO2, and then functionalized by NH2-PEG2000-COOH (PEG). The tumor-targeting group, folic acid (FA), was finally conjugated with the PEGylated MnO2 nanosheets. Then, doxorubicin (DOX), a chemotherapeutic agent, was loaded onto the modified nanosheets through a physical adsorption, which was designated as MnO2-PEG-FA/DOX. The prepared MnO2-PEG-FA/DOX nanosheets with good biocompatibility can not only efficiently deliver DOX to tumor cells in vitro and in vivo, leading to enhanced anti-tumor efficiency, but can also respond to a slightly acidic environment and high concentration of reduced glutathione (GSH), which caused degradation of MnO2 into manganese ions enabling magnetic resonance imaging (MRI). The longitudinal relaxation rate r1 was 2.26 mM(-1) s(-1) at pH 5.0 containing 2 mM GSH. These reduction and pH dual-responsive biodegradable nanosheets combining efficient MRI and chemotherapy provide a novel and promising platform for tumor-targeting theranostic application.

Chimeric antigen receptor (CAR) T therapy represents a form of immune cellular therapy with clinical efficacy and a specific target. A typical chimeric antigen receptor (CAR) construct consists of an antigen binding domain, a transmembrane domain, and a cytoplasmic domain. Nanobodies have been widely applied as the antigen binding domain of CAR-T due to their small size, optimal stability, high affinity, and manufacturing feasibility. The nanobody-based CAR structure has shown a proven function in more than ten different tumor-specific targets. After being transduced in Jurkat cells, natural killer cells, or primary T cells, the resulting nanobody-based CAR-T or CAR-NK cells demonstrate anti-tumor effects both in vitro and in vivo. Interestingly, anti-BCMA CAR-T modulated by a single nanobody or bi-valent nanobody displays comparable clinical effects with that of single-chain variable fragment (scFv)-modulated CAR-T. The application of nanobodies in CAR-T therapy has been well demonstrated from bench to bedside and displays great potential in forming advanced CAR-T for more challenging tasks.

Gold nanomaterials possess unique physical and chemical properties, which attracted much attention in recent years. As a new type of gold nanomaterials, gold nanostars (GNSTs) have been prepared and characterized in this study. GNSTs under near-infrared (NIR) light irradiation can exert not only cancer photothermal therapy via heat production but also photodynamic therapy via generation of reactive oxygen species. GNSTs were able to enter the cytoplasm as well as nuclei of human breast michigan cancer foundation-7 (MCF-7) cells. Under NIR light irradiation, GNSTs caused more severe DNA damage, arrest the cell cycle in G0/G1 phase, and reduce more cellular glutathione level, causing more severe apoptosis and cell death in vitro. Intratumoral injection of GNSTs with NIR light irradiation significantly inhibited tumor growth in vivo. In addition, GNSTs were demonstrated to be a contrast agent for X-ray imaging. All the in vitro and in vivo results showed that GNSTs can be used for the potential diagnosis and medical treatment of cancer.