Inflammation-Regulated Nanodrug Sensitizes Hepatocellular Carcinoma to Checkpoint Blockade Therapy by Reprogramming the Tumor Microenvironment.

Immune checkpoint blockade (ICB) utilizing programmed death ligand-1 (PD-L1) antibody is a promising treatment strategy in solid tumors. However, in fact, more than half of hepatocellular carcinoma (HCC) patients are unresponsive to PD-L1-based ICB treatment due to multiple immune evasion mechanisms such as the hyperactivation of inflammation pathway, excessive tumor-associated macrophages (TAMs) infiltration, and insufficient infiltration of T cells. Herein, an inflammation-regulated nanodrug was designed to codeliver NF-κB inhibitor curcumin and PD-L1 antibody to reprogram the tumor microenvironment (TME) and activate antitumor immunity.

Nanodrug regulates lactic acid metabolism to reprogram the immunosuppressive tumor microenvironment for enhanced cancer immunotherapy.

A majority of cancers fail to respond to immunotherapy due to the immunosuppressive tumor microenvironment (TME), and metabolic regulation of the TME has been a promising strategy to improve immunotherapy. Lactate is a key metabolic player in tumor immune response since its excess secretion aggravates tumor immune escape by favoring the polarization of tumor-associated macrophages (TAMs) to an immunosuppressive phenotype meanwhile impeding the tumor infiltration of the cytotoxic T lymphocyte. Here, we proposed a metabolic reprogramming mechanism to ameliorate tumor immunosuppression by using lonidamine and syrosingopine incorporated liposomes (L@S/L) to regulate lactate production and efflux.

Preliminary Study of MR and Fluorescence Dual-mode Imaging: Combined Macrophage-Targeted and Superparamagnetic Polymeric Micelles.

To establish small-sized superparamagnetic polymeric micelles for magnetic resonance and fluorescent dual-modal imaging, we investigated the feasibility of MR imaging (MRI) and macrophage-targeted in vitro. A new class of superparamagnetic iron oxide nanoparticles (SPIONs) and Nile red-co-loaded mPEG-Lys3-CA4-NR/SPION polymeric micelles was synthesized to label Raw264.7 cells.

Highly uniform and stable cerasomal microcapsule with good biocompatibility for drug delivery.

Efforts to improve the stability of liposomes have recently led to the development of organic-inorganic liposomal cerasomes. However, the uncontrollable size of cerasomes has greatly limited their biomedical applications. In this study, a novel strategy was introduced to fabricate hybrid liposomal cerasomes with high stability and uniform size.

Effect of PEG-PDLLA polymeric nanovesicles loaded with doxorubicin and hematoporphyrin monomethyl ether on human hepatocellular carcinoma HepG2 cells in vitro.

Objective: To evaluate the cytotoxicity of poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-PDLLA) nanovesicles loaded with doxorubicin (DOX) and the photosensitizer hematoporphyrin monomethyl ether (HMME) on human hepatocellular carcinoma HepG2 cells and to investigate potential apoptotic mechanisms.

Methods: PEG-PDLLA nanovesicles were simultaneously loaded with DOX and HMME (PEG-PDLLA-DOX-HMME), and PEG-PDLLA nanovesicles were loaded with DOX (PEG-PDLLA-DOX), HMME (PEG-PDLLA-HMME), or the PEG-PDLLA nanovesicle alone as controls. The cytotoxicity of PEG-PDLLA-DOX-HMME, PEG-PDLLA-DOX, PEG-PDLLA-HMME, and PEG-PDLLA against HepG2 cells was measured, and the cellular reactive oxygen species, percentage of cells with mitochondrial membrane potential depolarization, and apoptotic rate following treatment were determined.

Pigment epithelium-derived factor gene loaded in cRGD-PEG-PEI suppresses colorectal cancer growth by targeting endothelial cells.

Pigment epithelium-derived factor (PEDF) recombinant protein has been investigated in many kinds of solid tumors due to its potent antiangiogenic activity. However, the complexity of protein purification, instability of recombinant protein and requirement of repeated injections are obstacles for the recombinant PEDF therapy for solid tumors. We successfully synthesized polyethyleneglycol-polyetherimide (PEG-PEI) and cRGD-PEG-PEI which was coupled with a cyclic RGD peptide, a special ligand for integrin αvβ3 receptor, as the vehicle for PEDF gene therapy in this study.

Controllable labelling of stem cells with a novel superparamagnetic iron oxide-loaded cationic nanovesicle for MR imaging.

Objective: To investigate the feasibility of highly efficient and controllable stem cell labelling for cellular MRI.

Methods: A new class of cationic, superparamagnetic iron oxide nanoparticle (SPION)-loaded nanovesicles was synthesised to label rat bone marrow mesenchymal stem cells without secondary transfection agents. The optimal labelling conditions and controllability were assessed, and the effect of labelling on cell viability, proliferation activity and multilineage differentiation was determined.

Age-related decline in reendothelialization capacity of human endothelial progenitor cells is restored by shear stress.

Aging is associated with dysfunction of endothelial progenitor cells (EPCs), and shear stress has a beneficial impact on EPC function; however, the effects of aging and shear stress on the endothelial repair capacity of EPCs after arterial injury have not been reported. Here we investigated the influence of aging and shear stress on the reendothelialization capacity of human EPCs and the related molecular mechanism. Compared with EPCs isolated from young subjects, EPCs from the elderly displayed an impaired migration and adhesion in vitro and demonstrated a significantly reduced reendothelialization capacity in vivo after transplantation into nude mice with carotid artery denudation injury.

Detection of Pb²⁺ at attomole levels by using dynamic light scattering and unmodified gold nanoparticles.

Lead ion (Pb²⁺) accumulation in nature can affect the environment and human health severely. Thus, rapid and sensitive detection is of great importance. One-step detection of Pb²⁺ at attomole levels was realized by using dynamic light scattering (DLS) technique coupled with unmodified gold nanoparticles (AuNPs).

Dynamic-light-scattering-based sequence-specific recognition of double-stranded DNA with oligonucleotide-functionalized gold nanoparticles.

An ultrasensitive and simple dynamic-light-scattering (DLS) assay for the sequence-specific recognition of double-stranded DNA (dsDNA) was developed based on detection of the average diameter change of Au nanoparticle (AuNP) probes modified with oligonucleotides 5'-TTTCTCTTCCTT- CTCTTC-(T)(12)-SH-3' (Oligo 1) and 5'-TTCTTTCTTTTCTTTTTC-(T)(12)- SH-3' (Oligo 2). The target dsDNA was composed of two complementary oligonucleotides: 5'-AAAGAGAAGGAAGAGAAGAAGAAAGAAAAGAAAAAG-3' (Oligo 3) and 3'-TTTCTCTTCCTTCTCTTCTTCTTTCTTTTCTTTTTC-5' (Oligo 4). Hybridization of the two AuNPs-Oligo probes with the target dsDNA induced aggregation of the target dsDNA by forming triplex DNA, which accordingly increased the average diameter.

Plasmid-encapsulated polyethylene glycol-grafted polyethylenimine nanoparticles for gene delivery into rat mesenchymal stem cells.

Background: Mesenchymal stem cell transplantation is a promising method in regenerative medicine. Gene-modified mesenchymal stem cells possess superior characteristics of specific tissue differentiation, resistance to apoptosis, and directional migration. Viral vectors have the disadvantages of potential immunogenicity, carcinogenicity, and complicated synthetic procedures.

[Pilot study on MRI of human colon adenocarcinoma cells labeled with superparamagnetic iron oxide in vitro].

Objective: To study the feasibility of MRI of human colon adenocarcinoma cell line (Lovo) labeled with superparamagnetic iron oxide(SPIO) nanoparticles in vitro.

Methods: Lovo cells (5 × 10(5) and 1 × 10(6)) were cultured in medium containing different SPIO nanoparticles (50 microl and 500 microl). Transmission electron microscopy was used to observe cellular ultrastructure and to determine the uptake and distribution of particles in Lovo cells at 1-, 3-, 6-hours.

The use of folate-PEG-grafted-hybranched-PEI nonviral vector for the inhibition of glioma growth in the rat.

Combined treatment using nonviral agent-mediated enzyme/prodrug therapy and immunotherapy had been proposed as a powerful alternative method of cancer therapy. The present study was aimed to evaluate the cytotoxicity in vitro and the therapeutic efficacy in vivo when the cytosine deaminase/5-fluorocytosine (CD/5-FC) and TNF-related apoptosis-inducing ligand (TRAIL) genes were jointly used against rat C6 glioma cells. The potency of the FA-PEG-PEI used as a nonviral vector was tested in the FR-expressed C6 glioma cells and Wistar rats.

[Investigation into the controlled release behavior of gemcitabine-loaded nanovesicles].

Objective: To prepare gemcitabine-loaded nanovesicles and to observe its morphology, structure, particle size, and drug-release performance in vitro.

Methods: Diemulsion technique was used to prepare nanovesicles as carrier from amphiphilic block copolymer of poly (ethylene glycol)-block-poly (D, L-lactide), and gemcitabine was used as the model drug. The morphology of vesicles was determined by scanning electron microscope (SEM) and transmission electron microscope (TEM), and its drug loading (DL), encapsulation ratio (ER), and drug-release curve in vitro were detected by UV-Vis-NIR Spectrophotometer.

Synthesis and characterization of folate-PEG-grafted-hyperbranched-PEI for tumor-targeted gene delivery.

A great challenge for gene therapy is to develop a high efficient gene delivery system with low toxicity. Nonviral vectors are still attractive although the current agents displayed some disadvantages (i.e.

FG020326-loaded nanoparticle with PEG and PDLLA improved pharmacodynamics of reversing multidrug resistance in vitro and in vivo.

Aim: FG020326, a novel imidazole derivative, is a potent multidrug-resistance (MDR) modulator in vitro and in vivo. However, FG020326 is insoluble. PEDLLA-FG020326 is a FG020326-loaded nanoparticle formed with diblock copolymers of poly (ethylene glycol)-block-poly (D,L-lactic acid) (PEG:PDLLA, PEDLLA) that can solubilize FG020326.