Advanced melanoma can rarely be cured. Photodynamic therapy (PDT) readily eradicates the primary melanoma but has limited ability to destroy the spreading tumor cells unless supported by other combinative interventions to augment systemic antitumor immunity. Based on the previously synthesized penetration‐enhancing biomaterials, a topically administered nanoformulation is developed, which profoundly assists 5‐aminolevulinic acid (5‐ALA) in circumventing skin barrier to be selectively delivered to tumor cells. After endocytosis, accumulated 5‐ALA is efficiently metabolized to a photosensitizer protoporphyrin IX (PpIX) which stimulates a large production of cytotoxic reactive oxygen species (ROS) under illumination. Accompanied by the robust inflammatory responses followed by primary tumor destruction, CD4+CD8+ double positive T cells are highly boosted to harness host immunity to purge metastases in lymphoid organs. Compared with dacarbazine and programmed death 1 (PD‐1) antibody, this treatment in advanced melanoma murine models, achieves a striking curable rate of 90% without melanoma prognostic markers LDH and S‐100B detection, followed by a relapse‐free survival rate of 83.33% in 300 days. Moreover, the cured mice's immune system function recovers to an extent similar to healthy mice without prolonged or exaggerated inflammation. This study using the synergistic biomaterials approach may thus render 5‐ALA‐mediated PDT a potentially curative therapy for advanced melanoma in clinic.
It is not efficient enough using the current approaches for tumor-selective drug delivery based on the EPR effect and ligand-receptor interactions, and they have largely failed to translate into the clinic. Therefore, it is urgent to explore an enhanced strategy for effective delivery of anticancer agents. Clinically, many cancers require large amounts of glutamine for their continued growth and survival, resulting in circulating glutamine extraction by the tumor being much greater than that for any organs, behaving as a "glutamine trap". In the present study, we sought to elucidate whether the glutamine-trap effect could be exploited to deliver therapeutic agents to selectively kill cancer cells. Here, a macromolecular glutamine analogue, glutamine-functionalized branched polyethylenimine (GPI), was constructed as the carrier to deliver anti-CD47 siRNA for the blockage of CD47 "don't eat me" signals on cancer cells. The GPI/siRNA glutamine-rich polyplexes exhibited remarkably high levels of cellular uptake by glutamine-dependent lung cancer cells, wild-type A549 cells (A549), and its cisplatin-resistant cells (A549), specifically under glutamine-depleted conditions. It was noted that the glutamine transporter ASCT2 was highly expressed both on A549 and A549 but with almost no expression in normal human lung fibroblasts cells. Inhibition of ASCT2 significantly prevented the internalization of GPI polyplexes. These findings raised the intriguing possibility that the glutamine-rich GPI polyplexes utilize the ASCT2 pathway to selectively facilitate their cellular uptake by cancer cells. GPI further delivered anti-CD47 siRNA efficiently both in vitro and in vivo to downregulate the intratumoral mRNA and protein expression levels of CD47. CD47 functions as a "don't eat me" signal and binds to the immunoreceptor SIRPα inducing evasion of phagocytic clearance. GPI/anti-CD47 siRNA polyplexes achieved significant antitumor activities both on A549 and A549 tumor-bearing nude mice. Notably, it had no adverse effect on CD47-expressing red blood cells and platelets, likely because of selective delivery. Therefore, the glutamine-rich carrier GPI driven by the glutamine-trap effect provides a promising new strategy for designing anticancer drug delivery systems.
A new erythritol-producing yeast (strain BH010) was isolated in this study. Analysis of the D1/D2 domain of the 26S rDNA sequence, the ITS/5.8S rDNA sequence, and the 18S rDNA sequence allowed the taxonomic position of strain BH010 to be discussed and it was identified and named Moniliella sp. BH010. Physiological characteristics were described. Scanning electron micrography clearly indicated that the cells were cylindrical to elliptical with an average size of 5 × 10 μm when growing in liquid medium, and that pseudohyphae and blastoconidia were observed when cultivated in agar plates. The erythritol reductase genes were cloned, sequenced, and analyzed. BLAST analysis and multiple sequence alignment demonstrated that erythritol reductase genes of Moniliella sp. BH010 shared very high homology with that of Trichosporonoides megachiliensis SNG-42 except for the presence of introns. The deduced amino acid sequences showed high homology to the aldo–keto reductase superfamily.
Instant rice porridge produced through cooking, drying and a series of other processes possesses inferior sensory quality which is related to the gelatinization and retrogradation of rice starch. The effects of different enzyme treatments including α-amylase, β-amylase and neutral protease and different drying methods including hot air drying, freeze drying and freeze-hot air drying on gelatinization and retrogradation of instant rice porridge were investigated in this work utilizing rapid viscosity analyzer (RVA), scanning electron microscopy (SEM) and X-ray diffraction (XRD). As for enzyme treatments, rice porridge treated by α-amylase demonstrated the lowest viscosity value and the greatest porosity which suggested that α-amylase exceeded other two enzymes in maintaining gelatinization, inhibiting retrogradation and facilitating rehydration of instant rice porridge. For different drying methods, it was found that freeze drying was most advantageous to maintain gelatinization with the lowest viscosity and the greatest porosity. This study is especially helpful to gain initial insight into the development of instant rice porridge processing technology.Keywords: enzyme treatments, drying methods, instant rice porridge, gelatinization, retrogradation *To whom correspondence should be addressed. E-mail: xiao@tju.edu.cn IntroductionWith the accelerating pace of modern life, people's demand for convenience foods has become more and more pressing. Instant rice porridge is a kind of convenience foods which is made of rice through cooking, drying and a series of other processes. At present, a few instant rice porridge products are available on the market, but one major problem still exists, namely, the inferior sensory quality compared with traditional freshly cooked rice porridge. The inferior sensory quality of instant rice porridge includes long rehydration time and hard texture which affects consumer acceptability and blocks the promotion of instant rice porridge.The sensory quality of instant rice porridge is related to the gelatinization and retrogradation of rice starch, which is a major component of rice, accounting for more than 70% of the total weight. Gelatinized rice starch tends to retrograde during the drying and cooling process (Miles et al., 1985), thus affects the rehydration of instant rice porridge.Literature can be reviewed concerning the effect of
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