TCPP-Isoliensinine Nanoparticles for Mild-Temperature Photothermal Therapy.

PURPOSE: Photothermal therapy (PTT) is promising for the treatment of tumors due to its advantages including minimally invasive, easy implementation and selective localized treatment. However, single PTT suffers from several limitations, such as constrained light penetration and low delivery efficiency, typically leading to heterogeneous heating and incomplete elimination of cancer cells. Therefore, combination of PTT with other therapies, eg, chemotherapy is desirable in order to achieve synergistic effects in cancer treatment. METHODS: Here, we designed a new type of TCPP-Iso combined nanoparticle for synergetic therapy for breast cancer. Specifically, photothermal agent tetra(4-carboxyphenyl) porphine (TCPP) and anti-cancer drug isoliensinine (Iso) were encapsulated in PEG-b-PLGA polymeric nanoparticles through a precipitation process. RESULTS: The obtained NPs displayed well-controlled size and high stability over time. Tuning TCPP-Iso/polymer ratio, or total concentration of drug and polymers led to increased hydrodynamic radius of NPs from 65 to 108 nm without disturbing the narrow size distribution. Besides, the formed NPs showed a consequently cumulative release of TCPP and of Iso. The temperature elevation ability of both TCPP NPs and TCPP-Iso NPs was TCPP-concentration dependent. Solutions of TCPP NPs that contained equivalent amount of TCPP with respect to TCPP-Iso NPs, presented the same trend and exhibited non-obvious difference in temperature elevation under certain laser power. The viability of MDA-MB-231 cells treated with TCPP-Iso NPs could be inhibited effectively at a relatively mild temperature (42-43°C) compared to the other groups, which may minimize heat damage to the surrounding healthy tissues. CONCLUSION: The results indicate that the TCPP-Iso combined NPs showed hardly any toxicity to normal tissue cell line, but displayed an efficient synergistic effect for killing cancer cells under laser irradiation. Our study demonstrates that the successful combination of TCPP and Iso realized a synergistic therapy effect at a relatively mild temperature, and the insights obtained here shall be helpful for designing new combined PTT agents for cancer treatment.

One stone with two birds: Phytic acid-capped platinum nanoparticles for targeted combination therapy of bone tumors.

Targeted drug delivery to malignant bone lesions remains a challenging task in the treatment of bone tumors. In this article, we reported a naturally occurring phytic acid (PA) with both bone-targeting capability and anticancer activity. The PA-capped platinum nanoparticles showed high affinity to hydroxyapatite in vitro and in vivo, and maintained both the inherent anticancer ability of PA and photothermal effect of platinum nanoparticles. PA-capped nanoparticles displayed a 4-fold higher accumulation in the osteolytic lesions than sodium citrate-templated ones, and efficiently inhibited bone tumor growth and the tumor associated-osteolysis upon exposure to a near-infrared light. This study provides a novel and efficient strategy to prepare bone-targeted nanoparticles with inherent anticancer activity for combination therapy of malignant bone tumors.

Metabolomics reveals hippocampal metabolic fluctuations of postoperative fatigue syndrome and anti-fatigue effect of Carthamus tinctorius L extract in rat model.

Postoperative fatigue syndrome (POFS) is a common clinical complication followed by almost every major abdominal surgery. There is not a full explanation to the etiology of POFS, especially its central mechanism. Carthamus tinctorius L is a classic traditional Chinese medicine (TCM) which could exert the anti-fatigue effect on POFS. However, its mechanism is still lacking. Here, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOFMS) based metabonomic approach was used to characterize hippocampal metabolic fluctuations of POFS in a rat model induced by partial hepatectomy (PHx), and to evaluate the anti-fatigue effect of Carthamus tinctorius L extract (CTLE). With partial least-squares discriminant analysis for classification and selection of biomarkers, fifteen hippocampal metabolites related to POFS were identified, primarily involving alanine, aspartate and glutamate metabolism, valine, leucine and isoleucine degradation, purine metabolism, phenylalanine metabolism, tryptophan metabolism, phospholipid metabolism and fatty acid metabolism. With these altered metabolic pathways as possible drug targets, we systematically analyzed the protective effect of CTLE, which showed that CTLE could provide anti-fatigue effect on POFS through partially regulating the perturbed metabolic pathways. This study indicated that UHPLC-Q-TOFMS-based metabolomics provided a powerful tool to reveal hippocampal metabolic fluctuations of POFS and study the mechanism of TCM. This article is protected by copyright. All rights reserved.

Osteotropic peptide-mediated bone targeting for photothermal treatment of bone tumors.

The treatment of bone tumors is a challenging problem due to the inefficient delivery of therapeutics to bone and the bone microenvironment-associated tumor resistance to chemo- and radiotherapy. Here, we developed a bone-targeted nanoparticle, aspartate octapeptide-modified dendritic platinum-copper alloy nanoparticle (Asp-DPCN), for photothermal therapy (PTT) of bone tumors. Asp-DPCN showed much higher affinity toward hydroxyapatite and bone fragments than the non-targeted DPCN in vitro. Furthermore, Asp-DPCN accumulated more efficiently around bone tumors in vivo, and resulted in a higher temperature in bone tumors during PTT. Finally, Asp-DPCN-mediated PTT not only efficiently depressed the tumor growth but also significantly reduced the osteoclastic bone destruction. Our study developed a promising therapeutic approach for the treatment of bone tumors.