A natural anthocyanin-based multifunctional theranostic agent for dual-modal imaging and photothermal anti-tumor therapy.

Nowadays, cancer is one of the most serious diseases threatening the health of human beings, and imaging-guided photothermal therapy (PTT) is rapidly emerging as a potent oncotherapy strategy due to its unique advantages of high efficiency, noninvasiveness, visualization, and accuracy. In this study, a multifunctional nanoplatform based on gadolinium ion chelated natural anthocyanins (ACNs) is reported, which can be used not only as an excellent photoacoustic/magnetic resonance (PA/MR) dual-modal contrast agent but also for imaging-guided tumor PTT. The nanoparticles obtained have a suitable size, good dispersity, and physiological stability. The excellent biocompatibility and remarkable photothermal effect of the nanoparticles in vitro were demonstrated by CCK-8 assays and co-staining experiments. Moreover, the magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) results obtained in vivo showed that the nanoparticles were ideal dual-modal contrast agents whether given by intravenous or intratumoral injection. After intratumoral injection, the dual-modal PAI/MRI was used for determining the maximum diffusion time of the probe in the tumor site to guide laser treatment, achieving complete tumor elimination without normal tissue injury. Importantly, ACN is a natural compound extracted from black carrots, possessing native biocompatibility and biodegradability, which was further proved by the results of the detailed safety evaluation. Overall, the as-prepared nanoparticles displayed significant tumor diagnosis and treatment effects while mitigating biosafety concerns, and thus this was found to be a promising nanotherapeutic method for cancer treatment.

IR820 functionalized melanin nanoplates for dual-modal imaging and photothermal tumor eradication.

Melanin as an endogenous biomolecule is widely applied in the biomedical field, focusing especially on diagnostic imaging and photothermal therapy in cancer treatment. However, its photothermal conversion efficiency, a benchmark in tumor photothermal therapy (PTT), often could not satisfy PTT requirements to some degree, and this greatly influenced its use in photothermal cancer therapy. As for fluorescence imaging, a small-molecule NIR dye as a fluorescence probe is easily and rapidly metabolized in vivo, resulting in low accumulation in a tumor. To overcome these problems, we attempt to use melanin as a carrier to conjugate a fluorochrome, a recombinant small NIR dye IR820 nanoplatform containing melanin (MNP-PEG-IR820 abbreviated to MPI). The addition of IR820 not only enhances the PTT ability of the nanoplatform, but also endows the material with excellent NIR fluorescence behavior. Most importantly, the integration of fluorescence dye and melanin improves the circulation and stability performance of IR820 while reducing its toxicity in vivo, owing to the protectivity of melanin. Thus, the diagnostic capability is enhanced. Meanwhile, the behavior of the nanoplatform in PAI/PTT is significantly improved. The in vitro investigations reveal that the MPI NPs afford a potent PTT effect and ideal resistance to photobleaching. After intravenous injection, the MPI NPs display effective PTT tumor eradication in a Hep-2 tumor bearing mouse model with excellent dual NIR-I fluorescence/photoacoustic imaging guided phototherapy. Hence, our work shows the potential of MPI NPs as nano-theranostics for biomedical application to laryngocarcinoma.

Modified-FOLFIRINOX combined with deep regional hyperthermia in pancreatic cancer: a retrospective study in Chinese patients.

BACKGROUND: FOLFIRINOX chemotherapy displays significant survival improvements in patients with pancreatic cancer. However, toxicities have hampered enthusiasm for the use of FOLFIRINOX in full dose. In order to increase the tolerability, many researchers focused on the modification of FOLFIRINOX. On the other hand, hyperthermia (HT) has been considered as an effective ancillary treatment for cancer therapy. Up to now, there is no report evaluating combining deep regional hyperthermia (DRHT) with modified-FOLFIRINOX for pancreatic cancer patients. METHODS: In this study, we conducted a retrospective review of pancreatic cancer patients treated with the combination of new form modified-FOLFIRINOX and DRHT (BSD2000). Patients underwent chemotherapy that included low-dose irinotecan (70-130 mg/m2), oxaliplatin (65-70 mg/m2) on day 1 and 5-FU (2400 mg/m2 as a 46 h continuous infusion, no bolus) or capecitabine (CAP) (1000 mg/m2 twice daily on days 1-10) or tegafur, gimeracil and oteracil potassium (TS-1) (80-120 mg/d twice daily on days 1-10), 2-week schedule. Generally, DRHT treatment was performed weekly, 45 min for each time during chemotherapy. RESULTS: The patients receiving mFOLFIRINOX as the first line chemotherapy combining with DRHT, obtained an improvement in OS and PFS, 17 months (95% CI 1.97-32.03 months) and 4 months (95% CI 0-8.29 months) respectively. Overall, this combination regimen was safe; 17.6% patients suffered from grade 3/4 toxicities. CONCLUSIONS: In conclusion, we conducted a retrospective study combining mFOLFIRINOX and DRHT, which was well tolerated. The efficacy in the treatment of pancreatic cancer was encouraging, but further studies would be required to prove its merit, compared with conventional treatment.

Photoacoustic-imaging-guided therapy of functionalized melanin nanoparticles: combination of photothermal ablation and gene therapy against laryngeal squamous cell carcinoma.

Multimodality therapy under imaging-guidance is significant to improve the accuracy of cancer treatment. In this study, a photoacoustic imaging (PAI)-guided anticancer strategy based on poly-l-lysine functionalized melanin nanoparticles (MNP-PLL) was developed to treat laryngeal squamous cell carcinoma (LSCC). As a promising alternative to traditional therapies for LSCC, MNP-PLL/miRNA nanoparticles were combined with photothermal ablation against primary tumors and miR-145-5p mediated gene therapy for depleting the metastatic potential of tumor cells. Furthermore, taking advantage of the photoacoustic properties of melanin, PAI guided therapy could optimize the time point of NIR irradiation to maximize the efficacy of photothermal therapy (PTT). The in vitro and in vivo results proved that the combined treatments displayed the most significant tumor suppression compared with monotherapy. By integrating thermo-gene therapies into a theranostic nanoplatform, the MNP-PLL/miR-145-5p nanoparticles significantly suppressed the LSCC progression, indicating their great potential use for cancer therapy.

Ultrasmall endogenous biopolymer nanoparticles for magnetic resonance/photoacoustic dual-modal imaging-guided photothermal therapy.

Multi-modal imaging-guided photothermal therapy (PTT) has aroused extensive attention in biomedical research recently because it can provide more comprehensive information for accurate diagnosis and treatment. In this research, the manganese ion chelated endogenous biopolymer melanin nanoparticles were successfully prepared for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging-guided PTT. The obtained nanoparticles with an ultrasmall size of about 3.2 nm exhibited negligible cytotoxicity, high relaxivity for MRI, an excellent photothermal effect and PA activity. Moreover, in vivo MRI and PAI results all demonstrated that the nanoparticles began to diffuse in the blood after intratumoral injection into tumor-bearing mice and could spread throughout the whole tumor region at 3 h, indicating the optimal treatment time. The subsequent photothermal therapy of cancer cells in vivo was carried out and the result showed that tumor growth could be effectively inhibited without inducing any observed side effects. Besides, melanin as an endogenous biopolymer has native biocompatibility and biodegradability, and it can be excreted through both renal and hepatobiliary pathways after treatment. Therefore, the melanin-Mn nanoparticles may assist in better indicating the optimal treatment time, monitoring the therapeutic process and enhancing the therapeutic effect and showed great clinical translation potential for cancer diagnosis and therapy.

Type 2C protein phosphatase ABI1 is a negative regulator of strawberry fruit ripening.

Although a great deal of progress has been made toward understanding the role of abscisic acid (ABA) in fruit ripening, many components in the ABA signalling pathway remain to be elucidated. Here, a strawberry gene homologous to the Arabidopsis gene ABI1, named FaABI1, was isolated and characterized. The 1641bp cDNA includes an intact open reading frame that encodes a deduced protein of 546 amino acids, in which putative conserved domains were determined by homology analysis. Transcriptional analysis showed that the levels of FaABI1 mRNA expression declined rapidly during strawberry fruit development as evidenced by real-time PCR, semi-quantitative reverse transcription-PCR, and northern blotting analyses, suggesting that the Ser/Thr protein phosphatase PP2C1 encoded by FaABI1 may be involved in fruit ripening as a negative regulator. The results of Tobacco rattle virus-induced gene silencing and PBI121 vector-mediated overexpression suggested that the down- and up-regulation of FaABI1 mRNA expression levels in degreening strawberry fruit could promote and inhibit ripening, respectively. Furthermore, alteration of FaABI1 expression could differentially regulate the transcripts of a set of both ABA-responsive and ripening-related genes, including ABI3, ABI4, ABI5, SnRK2, ABRE1, CHS, PG1, PL, CHI, F3H, DFR, ANS, and UFGT. Taken together, the data provide new evidence for an important role for ABA in regulating strawberry fruit ripening in the processes of which the type 2C protein phosphatase ABI1 serves as a negative regulator. Finally, a possible core mechanism underlying ABA perception and signalling transduction in strawberry fruit ripening is discussed.

Frequency stability of a femtosecond optical parametric oscillator frequency comb.

Carrier-envelope-offset (CEO) and pulse-repetition frequencies of a Ti:sapphire-pumped femtosecond optical parametric oscillator were locked to uncertainties of 0.09 Hz and 0.16 mHz respectively, with the CEO beat signal linewidth being stabilized to 15 Hz (instrument limited). In-loop phase-noise power spectral density measurements showed a contribution of our servo electronics to the comb-line frequency uncertainty of up to 110 Hz. Complementary time-series data implied an in-loop comb instability of 2 x 10(-11) (1-s gate time), matching the Rb-stabilized reference used and verifying that dual servo-control of the CEO and repetition frequencies was effective in stabilizing the comb to at least this precision.