Multifunctional nanoparticles have been reported for cancer detection and treatment currently. However, the accurate diagnosis and efficient treatment for tumors are still not satisfied. Here we report on the development of targeted phase change multimodal polymeric nanoparticles for the imaging and treatment of HER2-positive breast cancer.Methods: We evaluated the multimodal imaging capabilities of the prepared nanoparticles in vitro using agar-based phantoms. The targeting performance and cytotoxicity of the nanoparticles were examined in cell culture using SKBR3 (over-expressing HER2) and MDA-MB-231 (HER2 negative) cells. We then tested the magnetic resonance (MR)/ photoacoustic (PA)/ ultrasound (US)/ near-infrared fluorescence (NIRF) multimodal imaging properties and photothermal effect of the nanoparticles in vivo using a SKBR3 breast xenograft model in nude mice. Tissue histopathology and immunofluorescence were also conducted.Results: Both in vitro and in vivo systematical studies validated that the hybrid nanoparticles can be used as a superb MR/US/PA/NIRF contrast agent to simultaneously diagnose and guide tumor photothermal therapy (PTT). When irradiated by a near infrared laser, the liquid PFP vaporizes to a gas, rapidly expelling the contents and damaging surrounding tissues. The resulting micro-sized bubbles provide treatment validation through ultrasound imaging. Localization of DIR and SPIO in the tumor region facilitate photothermal therapy for targeted tumor destruction. The mice treated with HER2 targeted nanoparticles had a nearly complete response to treatment, while the controls showed continued tumor growth.Conclusion: This novel theranostic agent may provide better diagnostic imaging and therapeutic potential than current methods for treating HER2-positive breast cancer.

BackgroundA sedentary lifestyle and poor diet are risk factors for the progression of non-alcoholic fatty liver disease. However, the pathogenesis of hepatic lipid accumulation is not completely understood. Therefore, the present study explored the effects of dietary supplementation of various ratios of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on a high-fat diet-induced lipid metabolism disorder and the concurrent liver damage.MethodsUsing high-fat diet-fed C57BL/6 J mice as the animal model, diets of various ratios of DHA/EPA (2:1, 1:1, and 1:2) with an n-6/n-3 ratio of 4:1 were prepared using fish and algae oils enriched in DHA and/or EPA and sunflower seed oils to a small extent instead of the high-fat diet.ResultsSignificantly decreased hepatic lipid deposition, body weight, serum lipid profile, inflammatory reactions, lipid peroxidation, and expression of adipogenesis-related proteins and inflammatory factors were observed for mice that were on a diet supplemented with DHA/EPA compared to those in the high-fat control group. The DHA/EPA 1:2 group showed lower serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol levels, lower SREBP-1C, FAS, and ACC-1 relative mRNA expression, and higher Fra1 mRNA expression, with higher relative mRNA expression of enzymes such as AMPK, PPARα, and HSL observed in the DHA/EPA 1:1 group. Lower liver TC and TG levels and higher superoxide dismutase levels were found in the DHA/EPA 2:1 group. Nonetheless, no other notable effects were observed on the biomarkers mentioned above in the groups treated with DHA/EPA compared with the DHA group.ConclusionsThe results showed that supplementation with a lower DHA/EPA ratio seems to be more effective at alleviating high-fat diet-induced liver damage in mice, and a DHA/EPA ratio of 1:2 mitigated inflammatory risk factors. These effects of n-3 polyunsaturated fatty acids (PUFA) on lipid metabolism may be linked to the upregulation of Fra1 and attenuated activity of c-Jun and c-Fos, thus ultimately reducing the severity of the lipid metabolism disorder and liver damage to some extent.

The commonly used ultrasound (US) molecular probes, such as targeted microbubbles and perfluorocarbon emulsions, present a number of inherent problems including the conflict between US visualization and particle penetration. This study describes the successful fabrication of phase changeable folate-targeted perfluoropentane nanodroplets (termed FA-NDs), a novel US molecular probe for tumor molecular imaging with US. Notably, these FA-NDs can be triggered by low-intensity focused US (LIFU) sonication, providing excellent US enhancement in B-mode and contrast-enhanced US mode in vitro. After intravenous administration into nude mice bearing SKOV3 ovarian carcinomas, 1,1′-dioctadecyl-3,3,3′,3′ -tetramethylindotricarbocya-nine iodide-labeled FA-NDs were found to accumulate in the tumor region. FA-NDs injection followed by LIFU sonication exhibited remarkable US contrast enhancement in the tumor region. In conclusion, combining our elaborately developed FA-NDs with LIFU sonication provides a potential protocol for US molecular imaging in folate receptor-overexpressing tumors.

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

Background Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers. Results The as-synthesized nanoplatforms penetrated deeply into the interior region of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment. Conclusions This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment. Graphical Abstract

Magnetic hyperthermia is a promising minimally invasive technique for tumor therapy which has drawn much attention.

BackgroundAs the protein-laden by-product, red blood cells (RBCs) from poultry blood is a potential source of protein used as food and feed ingredient. However, RBC was currently underutilized. Therefore, it is an urgent need to develop feasible and cost-effective methods for converting poultry waste into nutritional and functional products.ResultsTo take full advantage of this poultry waste, peptide hydrolysate was produced by deep controllable bioconversion of RBC, by means of synergistic combination of neutrase and flavourzyme. In this work, the functional properties and antioxidant activity of peptide hydrolysate were also characterized. The degree of hydrolysis (DH) was optimized using response surface methodology, and optimal hydrolysis conditions were found to be: temperature 51 °C, substrate concentration 14% (w/v), initial pH 7.0, and time 7.5 h. The red blood cell hydrolysate (RBCH) obtained not only possessed plentiful small peptides (< 3 kDa, 68.14%), but also was abundant in essential amino acids, accounting for over 50% of total amino acids. In addition to its excellent solubility (> 80%), emulsifying and foaming properties, RBCH also exhibited notable antioxidant activities, such as DPPH (2,2-diphenyl− 1-picrylhydrazyl) radical-scavenging activity (IC50, 4.16 mg/mL), reducing power, metal chelating ability and inhibiting lipid peroxidation.ConclusionsRBCH enriched in small peptides has the potential to be a new food additive with outstanding functional and antioxidant properties, and a process was established for converting poultry waste into peptide hydrolysate using neutrase and flavourzyme.Electronic supplementary materialThe online version of this article (10.1186/s12896-018-0475-5) contains supplementary material, which is available to authorized users.

The construction of high‐performance nanotheranostic agent with Food and Drug Administration (FDA)‐approved materials for efficient treatment of breast cancer is still of great challenge. This work reports, for the first time, on the elaborate integration of two FDA‐approved materials together to construct a multifunctional core/shell‐structured “nanococktail” for cancer theranostics. The biocompatible Prussian blue nanoparticles with high photothermal‐conversion performance are coated by poly(lactic‐co‐glycolic acid) followed by further surface targeting engineering (folic acid conjugation). The anticancer drug paclitaxel is concurrently encapsulated into the nanocarrier with high efficiency and capacity. Especially, these “nanococktails” act as the desirable contrast agents for photoacoustic/magnetic resonance imaging dual‐mode diagnostic imaging, providing the potential for guidance and monitoring during the therapeutic process, which has been systematically demonstrated both in vitro and in vivo. Importantly, these “nanococktails” have demonstrated their high performance in synergistic in vivo photothermal therapy and chemotherapy against breast cancer tumor xenograft. This work not only provides a high‐performance theranostic “nanococktail” platform for efficient theranostic treatment of cancer but also paves a new way for the integration of various functional moieties together for realizing the specific diagnostic imaging‐guided and synergistic cancer therapy.