Cancer cell membrane-coated nanoparticles for bimodal imaging-guided photothermal therapy and docetaxel-enhanced immunotherapy against cancer

Background Mono-therapeutic modality has limitations in combating metastatic lesions with complications. Although emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. The rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer. Results Poly lactic-co-glycolic acid (PLGA, 50 mg) nanospheres were constructed with photothermal transduction agents (PTAs)-Prussian blue (PB, 2.98 mg) encapsulated in the core and chemotherapeutic docetaxel (DTX, 4.18 mg)/ immune adjuvant-imiquimod (R837, 1.57 mg) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated “M@P-PDR”), which acted as “Nano-targeted cells” to actively accumulate in tumor sites, and were guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by the immune adjuvant R837, the maturation rate of DCs increased by 4.34-fold compared with that of the control. In addition, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving the immunosuppressive TME. The proportion of M2-TAMs decreased from 68.57% to 32.80%, and the proportion of M1-TAMs increased from 37.02% to 70.81%. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased from 17.33% (control) to 35.5%. Primary tumors and metastasis were significantly inhibited when treated with “Nano-targeted cells”-based cocktail therapy. Conclusion “Nano-targeted cells”-based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/recurrence. Graphical Abstract

Radiolabeled Silicon-Rhodamines as Bimodal PET/SPECT-NIR Imaging Agents

Radiolabeled fluorescent dyes are decisive for bimodal imaging as well as highly in demand for nuclear- and optical imaging. Silicon-rhodamines (SiRs) show unique near-infrared (NIR) optical properties, large quantum yields and extinction coefficients as well as high photostability. Here, we describe the synthesis, characterization and radiolabeling of novel NIR absorbing and emitting fluorophores from the silicon-rhodamine family for use in optical imaging (OI) combined with positron emission tomography (PET) or single photon emission computed tomography (SPECT), respectively. The presented photostable SiRs were characterized using NMR-, UV-Vis-NIR-spectroscopy and mass spectrometry. Moreover, the radiolabeling conditions using fluorine-18 or iodine-123 were extensively explored. After optimization, the radiofluorinated NIR imaging agents were obtained with radiochemical conversions (RCC) up to 70% and isolated radiochemical yields (RCY) up to 54% at molar activities of g.t. 70 GBq/µmol. Radioiodination delivered RCCs over 92% and allowed to isolate the 123I-labeled product in RCY of 54% at a molar activity of g.t. 7.6 TBq/µmol. The radiofluorinated SiRs exhibit in vitro stabilities g.t. 70% after two hours in human serum. The first described radiolabeled SiRs are a promising step toward their further development as multimodal PET/SPECT-NIR imaging agents for planning and subsequent imaging-guided oncological surgery.

Artificial “Nano-Targeted Cells” for Bimodal Imaging-Guided Tumor Cocktail Therapy

Background: Single therapeutic modality always has its limitations in combating metastatic lesions with complicacy. Although the emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. Rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer.Results: Poly lactic-co-glycolic acid (PLGA) nanospheres were constructed with photothermal transduction agents (PTAs)- Prussian blue (PB) encapsulated in the core and chemotherapeutic docetaxel (DTX)/ immune adjuvant- imiquimod (R837) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated as “M@P-PDR”), which acted as “Nano-targeted cells” to actively accumulate in tumor sites, which was guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by immune adjuvant R837, the maturation of DCs were promoted. Besides, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving immunosuppressive TME. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased. The primary tumors and metastasis were significantly inhibited when treated with “Nano-targeted cells” based cocktail therapy.Conclusion: “Nano-targeted cells” based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/ recurrence.

Red Fluorescent Emissive Gd-Phenolic Nanoparticles for In Vivo Fluorescence and Magnetic Resonance Bimodal Imaging

Due to the combination of the high resolution of fluorescence imaging and the no limitation in penetration depth of magnetic resonance imaging, dual-mode imaging of magnetic resonance and fluorescence (MR/FI) have attracted extensive research in recent years. Herein, a novel MR/FI bimodal imaging probe is facile fabricated by attaching the rhodamine fluorophore covalently to the surface of the Gd-phenolic coordination polymer nanoparticles. The contents of Gd3+ and RB of the as prepared probe are calculated to be 8.2% and 12.5%. The quantum yield of the probe is about 8.84% as well as red fluorescent emissive. The longitudinal r1 value is 6.94 mM−1 s−1 and the ratio r2/r1 is very low and about 1.22. Subsequently, the and MR imaging and fluorescence both in vitro and In Vivo are performed. The metabolic pathways In Vivo are inferred by studying the bio-distribution of the probe in major organs. The as-prepared probe exhibits excellent imaging performance and biocompatibility, which is conducive to its further application.

The Bimodal Neutron and X-ray Imaging Driven by a Single Electron Linear Accelerator

Both X-ray imaging and neutron imaging are essential methods in non-destructive testing. In this work, a bimodal imaging method combining neutron and X-ray imaging is introduced. The experiment is based on a small electron accelerator-based photoneutron source that can simultaneously generate the following two kinds of radiations: X-ray and neutron. This identification method utilizes the attenuation difference of the two rays’ incidence on the same material to determine the material’s properties based on dual-imaging fusion. It can enhance the identification of the materials from single ray imaging and has the potential for widespread use in on-site, non-destructive testing where metallic materials and non-metallic materials are mixed.

Low-dose X-ray enhanced tumor accumulation of theranostic nanoparticles for high-performance bimodal imaging-guided photothermal therapy

Background Theranostic nanoparticles (NPs) have achieved rapid development owing to their capacity for personalized multimodal diagnostic imaging and antitumor therapy. However, the efficient delivery and bulk accumulation of NPs in tumors are still the decisive factors in improving therapeutic effect. It is urgent to seek other methods to alters tumor microenvironment (like vascular permeability and density) for enhancing the efficiency of nanoparticles delivery and accumulation at the tumor site. Methods Herein, we developed a Raman-tagged hollow gold nanoparticle (termed as HAuNP@DTTC) with surface-enhanced Raman scattering (SERS) property, which could be accumulated efficiently in tumor site with the pre-irradiation of low-dose (3 Gy) X-ray and then exerted highly antitumor effect in breast cancer model. Results The tumor growth inhibition (TGI) of HAuNP@DTTC-induced photothermal therapy (PTT) was increased from 60% for PTT only to 97%, and the lethal distant metastasis of 4T1 breast cancer (such as lung and liver) were effectively inhibited under the X-ray-assisted PTT treatment. Moreover, with the strong absorbance induced by localized surface plasmon resonance in near-infrared (NIR) region, the signals of Raman/photoacoustic (PA) imaging in tumor was also significantly enhanced after the administration of HAuNP@DTTC, indicating it could be used as the Raman/PA imaging and photothermal agent simultaneously under 808 nm laser irradiation. Conclusions Our studied of the as-prepared HAuNP@DTTC integrated the Raman/PA imaging and PTT functions into the single platform, and showed the good prospects for clinical applications especially with the low-dose X-ray irradiation as an adjuvant, which will be a productive strategy for enhancing drug delivery and accumulation in tumor theranostics. Graphic Abstract

A novel ANG-BSA/BCNU/ICG MNPs integrated for targeting therapy of glioblastoma

Nanomedicine can improve the traditional disease treatment by actively targeting and enhancing the controlled release of drugs in the focus tissue in vivo, moreover the integration of diagnosis and treatment can be achieved by using tracer molecules to indicate the accumulation of nanodrugs in the focus. However ， almost all chemotherapeutic drugs and gene drugs failed to effectively treat glioblastoma (GBM) on account of the existence of blood-brain barrier (BBB) which play a role in GBM. So far, the survival rate of patients with GBM has been hardly improved. In the present study, we constructed an integrated nanoprobe based on albumin nanoparticles (NPs) for targeted diagnosis and treatment of GBM. The nanoprobe consists of albumin-coated superparamagnetic iron oxide (SPIO), Carmustine (BCNU) and indocyanine green (ICG) to achieve bimodal imaging and drug delivery. And the surface-coupled Angopep-2 (ANG, TFFYGGSRGKRNNFKTEEY) polypeptide can specifically bind to low density lipoprotein receptor-related protein (LRP), which is overexpressed in BBB and GBM cells. In the in vitro experiments, we verified that the targeting ability of nanoprobes to GBM cells was significantly better than that of the control group. In addition, in the in vivo experiments, nanoprobes significantly increased the accumulation of brain tumors compared with the control group. Cell killing of GBM cells (U87MG) with ANG-BSA/BCNU/ICG magnetic NPs shows a higher inhibitory effect compared with controls. This novel targeting imaging and drug delivery system provides an efficient strategy for targeted therapy and intraoperative localization of GBM.