Research advances on antitumor mechanism of NK cells and its application in cancer targeted therapy / 药学学报

Natural killer (NK) cells, as an essential part of innate immunity, can directly identify and kill tumor cells after being activated by the synergistic action of surface inhibitory receptors and activated receptors. It can secrete cytokines to recruit dendritic cells (DCs), induce DCs maturation and enhance adaptive immune response. It can target cancer stem cells (CSCs) and circulating tumor cells (CTCs) to inhibit cancer metastasis. NK cells have a unique inflammatory tendency, which can respond to cytokines and chemokines released from tumor sites and migrate to tumor sites, making them occupy an important advantage in cancer targeted therapy. The research on cancer targeted therapy of NK cells as drug delivery carriers, NK cell membrane-coated biomimetic nanoparticles, and NK cell extracellular vesicles (NKEVs) has attracted more and more attention. The article will focus on the mechanism of NK cells inhibiting cancer, and summarize the research progress of cancer targeted therapy of NK cells.

Research progress on the role and intervention strategies of NRP1 in colorectal cancer / 药学学报

Colorectal cancer (CRC) is one of the most common malignant tumors in the world, and its incidence and mortality are among the top three of all malignant tumors. In recent years, CRC is becoming more common in younger patients. Currently, surgery is the main or first treatment of early stage CRC, however, up to 50% patients have recurrence and metastasis post-surgery. While chemotherapy and radiotherapy are often used as adjuvant treatment after surgery or as main treatment options for late stage CRC, they usually induce severe adverse effects. Safe and effective treatments for CRC are still lacking. Therefore, it is essential to discover new therapies for CRC. Neuropilin 1 (NRP1), as a transmembrane glycoprotein, is reported to highly express in CRC, and its overexpression is demonstrated to be closely related to the occurrence and development of CRC. NRP1 is involved in angiogenesis, tumor growth, autophagy, and lipid metabolism, which is expected to be a potential new target for the treatment of CRC. This paper reviews the role of NRP1 in CRC, including its molecular structure, expression in CRC, as well as its connection with autophagy and metabolism. The regulatory factors of NRP1 in CRC were introduced, including vascular endothelial growth factor (VEGF), semaphorin 3A (SEMA3A), transforming growth factor-β (TGF-β), etc. The potential intervention strategies of CRC targeting NRP1 were summarized in order to provide reference for the diagnosis and prevention of CRC.

Cell membrane-based nanoparticles: a new biomimetic platform for tumor diagnosis and treatment

Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems (fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles (CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.

Radio-graphene in Theranostic Perspectives / 대한핵의학회잡지

Owing to its unique physicochemical properties such as high surface area, notable biocompatibility, robust mechanical strength, high thermal conductivity, and ease of functionalization, 2D-layered graphene has received tremendous attention as a futuristic nanomaterial and its-associated research has been rapidly evolving in a variety of fields.With the remarkable advances of graphene especially in the biomedical realm, in vivo evaluation techniques to examine in vivo behavior of graphene are largely demanded under the hope of clinical translation. Many different types of drugs such as the antisense oligomer and chemotherapeutics require optimal delivery conveyor and graphene is now recognized as a suitable candidate due to its simple and high drug loading property. Termed as ‘ radio-graphene’, radioisotope-labeled graphene approach was recently harnessed in the realm of biomedicine including cancer diagnosis and therapy, contributing to the acquisition of in vivo information for targeted drug delivery. In this review, we highlight current examples for bioapplication of radiolabeled graphene with brief perspectives on future strategies in its extensive bio- or clinical applications.

Functional investigation of a new targeting gene delivery system of miRNA-34a nano-complexes into prostate cancer cell lines / 药学实践杂志

Objective To construct a gene delivery carrier with aptamer-polyethylene glycol-dendrimer-polyamidoamine (APT-PEG-PAMAM) ,forming nanoparticles to specifically target prostate cancer cell lines ,carrying prostate cancer cell pro-liferative suppressor microRNA :miRNA-34a .We investigated the transfection efficiency of this gene delivery system as well as functionally studied its inhibitory effect on prostate cancer (PCa) cell proliferation .Methods The construction of APT-PEG-PAMAM gene carrier was identified and confirmed by nuclear magnetic resonance (NMR) .The nano-complex sizes and zeta potential of APT-PEG-PAMAM gene carrier complexes were measured by zeta sizer .The efficiency of gene transfection of APT-PEG-PAMAM /miRNA nano-complexes were investigated by measuring the expression miRNA-34a in prostate cancer cells (PC3 and LNCaP);the PCa specific cell proliferation inhibition of APT-PEG-PAMAM / miRNA-34a nano-complexes were investigated by measuring CCK-8 cell proliferation inhibition experiments by comparing with APT-PEG-PAMAM and APT-PEG-PAMAM /miRNA-34a nano-complexes .Results NMR results demonstrated that APT-PEG-PAMAM /miRNA-34a nano-complexes were successfully synthesized by structural identification .Qualitative and quantitative transfection efficien-cy experiments data show that the cellular uptake of vectors were concentration-dependent ,after the APT further modified it significantly and increased the LNCaP cell transfection efficiency and specificity of PCa cells targeting ability .CCK8 cell prolif-eration assay data indicated that APT-PEG-PAMAM/miRNA-34a has the anti-PCa cells effect .Conclusion APT-PEG-PAM-AM/miRNA-34a may prove to see its efficacy for near future in pre-clinical and clinical study on the treatment of PCa .

Targeting Orthotopic Glioma in Mice with Genetically Engineered Salmonella typhimurium

OBJECTIVE: With the growing interests of bacteria as a targeting vector for cancer treatment, diverse genetically engineered Salmonella has been reported to be capable of targeting primary or metastatic tumor regions after intravenous injection into mouse tumor models. The purpose of this study was to investigate the capability of the genetically engineered Salmonella typhimurium (S. typhimurium) to access the glioma xenograft, which was monitored in mouse brain tumor models using optical bioluminescence imaging technique. METHODS: U87 malignant glioma cells (U87-MG) stably transfected with firefly luciferase (Fluc) were implanted into BALB/cAnN nude mice by stereotactic injection into the striatum. After tumor formation, attenuated S. typhimurium expressing bacterial luciferase (Lux) was injected into the tail vein. Bioluminescence signals from transfected cells or bacteria were monitored using a cooled charge-coupled device camera to identify the tumor location or to trace the bacterial migration. Immunofluorescence staining was also performed in frozen sections of mouse glioma xenograft. RESULTS: The injected S. typhimurium exclusively localized in the glioma xenograft region of U87-MG-bearing mouse. Immunofluorescence staining also demonstrated the accumulation of S. typhimurium in the brain tumors. CONCLUSION: The present study demonstrated that S. typhimurium can target glioma xenograft, and may provide a potentially therapeutic probe for glioma.

Cancer -Targeted MR Molecular Imaging

Magnetic resonance (MR) imaging has been widely used in the clinic because of the benefit of high spatial and temporal resolution, and the excellent anatomical tissue contrast. Cancer-targeted MR molecular imaging comprises 3 major components: a relevant molecular target which is specifically highly expressed on the membrane of the cancer cell; a target specific imaging probe which is composed of superparamagnetic iron oxide nanoparticle coreconjugated target specific ligand such as antibody, peptide, and molecules; MR imaging hardware and software which are sensitive to the imaging probe. Among the various molecular targets, HER2/neu receptor antibody, folic acid, and arginine-glycine-aspartic acid (RGD) are well known targeting ligands. The sensitivity of the cancer-targeted MR imaging is affected by the magnetic susceptibility of the T2 contrast agent, resolution of the image, targeting efficiency of the imaging probe, and image acquisition pulse sequence. Recently, successful cancer-targeted MR imaging with T1 contrast agent and cancer-specific molecular MR imaging using innate contrast of the cancer cell by chemical exchange phenomenon without using the imaging probe has been introduced. Cancer-targeted MR molecuar imaging is a robust diagnostic method to detect cancer at the cellular stage of the cancer development and it would help improve early detection rate of the cancer.