These results reveal that lime mint essential oil and β-caryophyllene are considered to be valuable as potential skin-whitening agents.
Intra-tumor heterogeneity is widely accepted as one of the key factors, which hinders cancer patients from achieving full recovery. Especially, cancer stem cells (CSCs) may exhibit self-renewal capacity, which makes it harder for complete elimination of tumor. Therefore, simultaneously inhibiting CSCs and non-CSCs in tumors becomes a promising strategy to obtain sustainable anticancer efficacy. Salinomycin (Sal) was reported to be critical to inhibit CSCs. However, the poor bioavailability and catastrophic side effects brought about limitations to clinical practice. To solve this problem, we previously constructed gelatinase-stimuli nanoparticles composed of nontoxic, biocompatible polyethylene glycol-polycaprolactone (PEG-PCL) copolymer with a gelatinase-cleavable peptide Pro-Val-Gly-Leu-Iso-Gly (PVGLIG) inserted between the two blocks of the copolymer. By applying our "smart" gelatinaseresponsive nanoparticles for Sal delivery, we have demonstrated specific accumulation in tumor, anti-CSCs ability and reduced toxicity of Sal-NPs in our previous study. In the present study, we synthesized Sal-Docetaxel-loaded gelatinase-stimuli nanoparticles (Sal-Doc NP) and confirmed single emulsion as the optimal method of producing Sal-Doc NPs (Sal-Doc SE-NP) in comparison with nanoprecipitation. Sal-Doc SE-NPs inhibited both CSCs and non-CSCs in mice transplanted with cervical cancer, and might be associated with enhanced restriction of epithelial-mesenchymal transition (EMT) pathway. Besides, the tumorigenic capacity and growing speed were obviously suppressed in Sal-Doc-SE-NPstreated group in rechallenge experiment. Our results suggest that Sal-Doc-loaded gelatinase-stimuli nanoparticles could be a promising strategy to enhance antitumor efficacy and reduce side effects by simultaneously suppressing CSCs and non-CSCs.
Therapeutic responses to chimeric antigen receptor (CAR) T cell therapy in patients with limited treatment options have been appealing in several clinical trials. However, the efficacy of CAR‐T therapy has been challenged by several obstacles when treating patients with solid tumors, such as severe toxicities, restricted access to tumor sites, suboptimal therapeutic persistence, and manufacturing issues. Nanotechnology has the advantages of protecting CAR‐T cells from being suppressed by tumor microenvironment (TME) and favorably adapting immune‐modulating drugs’ pharmacokinetics by modifying their spatiotemporal release profiles. Loaded with nanoparticles and packed onto CAR‐T cells, immune‐modulating drugs can be delivered to the tumor site and lymph node more efficiently, stimulating the expansion and activity of CAR‐T cells. To protect normal tissues from the nonspecific toxicity of the activated CAR‐T cells, formulations are optimized toward tumor targeting delivery of nanotechnology. This review summarizes the nanotechnology strategies to improve the safety and efficacy of CAR‐T therapy. In addition, the unsolved problems existing in the clinical application of CAR‐T therapy are focused on, where study and exploration by the way of nanotechnology is needed.
Chemotherapy has been one of the major standard treatments for a variety of cancers. cis-Dichlorodiamminoplatiunum (II) (cisplatin, CDDP), as one of the anticancer agents, demonstrated excellent efficacy against tumor and has been an indispensable component in chemotherapy, chemoradiation, chemo-molecular targeted therapy and chemo-immunotherapy. However, its therapeutic concentration was limited since its inevitable toxicity. Previously, we have constructed CDDPloaded nanoparticles (NPs) with mixture of poly(ethyleneglycol)-polycaprolactone (PEG-PCL) and polycarprolactone (HOPCL) by a facile method. The most optimal proportion of the two copolymers was selected through a series of physical, chemical, cytological and histological evaluations. In the present study, we explored the mechanisms of NPs and observed the in vivo antitumor effect after administrating CDDP-loaded PEG-PCL NPs. Positron emission tomography as well as computed tomography (PET/CT) were adopted for detecting tumoral metabolic activity. Images from fluorescence microscope revealed superior cellular uptake of CDDP-loaded NPs with rhodamine B aggregated intracellularly in cancer cells. Similar apoptotic rates between free CDDP group and CDDP-loaded NPs group was measured by flow cytometry. Tumor volumes and murine weights confirmed the superiority of CDDP-loaded NPs in therapeutic efficacy as compared with free CDDP. Blood tests showed milder side effects in CDDP-loaded nanoparticle group. PET/CT images illustrated less uptake intensity of FDG in mice received CDDP-loaded NPs than free CDDP. Our results suggest that PEG-PCL/PCL NPs could be a promising antitumor drug carrier for CDDP delivery with solid efficacy and minor side effects.
In this study, the tumor-targeted MRI contrast agent was prepared with gelatinase-stimuli nanoparticles (NPs) and Omniscan (Omn) by double emulsion method. The size, distribution, morphology, stability, drug loading, and encapsulation efficiency of Omn-NPs were characterized. The macroscopic and microscopic morphological changes of NPs in response to gelatinases (collagenases IV) were observed. The MR imaging using Omn-NPs as a contrast agent was evaluated in the oral squamous cell carcinoma models with Omn as a control. We found clear evidence that the Omn-NPs were transformed by gelatinases and the signal of T1-weighted MRI sequence showed that the tumor-to-background ratio was significantly higher in Omn-NPs than in Omn. The peak point of time after injection was much later for Omn-NPs than Omn. This study demonstrates that Omn-NPs hold great promise as MRI contrast agent with improved specificity and prolonged circulation time based on a relatively simple and universal strategy.
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