Biological Synthesis of Bioactive Gold Nanoparticles from Inonotus obliquus for Dual Chemo-Photothermal Effects against Human Brain Cancer Cells

The possibility for an ecologically friendly and simple production of gold nanoparticles (AuNPs) with Chaga mushroom (Inonotus obliquus) (Ch-AuNPs) is presented in this study. Chaga extract’s reducing potential was evaluated at varied concentrations and temperatures. The nanoparticles synthesized were all under 20 nm in size, as measured by TEM, which is a commendable result for a spontaneous synthesis method utilizing a biological source. The Ch-AuNPs showed anti-cancer chemotherapeutic effects on human brain cancer cells which is attributed to the biofunctionalization of the AuNPs with Chaga bioactive components during the synthesis process. Further, the photothermal ablation capability of the as-prepared gold nanoparticles on human brain cancer cells was investigated. It was found that the NIR-laser induced thermal ablation of cancer cells was effective in eliminating over 80% of the cells. This research projects the Ch-AuNPs as promising, dual modal (chemo-photothermal) therapeutic candidates for anti-cancer applications.     

Piperlongumine as a Neuro-Protectant in Chemotherapy Induced Cognitive Impairment

Advances in the early diagnosis and treatment have led to increases in breast cancer survivorship. Survivors report cognitive impairment symptoms such as loss of concentration and learning and memory deficits which significantly reduce the patient’s quality of life. Additional therapies are needed to prevent these side effects and, the precise mechanisms of action responsible are not fully elucidated. However, increasing evidence points toward the use of neuroprotective compounds with antioxidants and anti-inflammatory properties as tools for conserving learning and memory. Here, we examine the ability of piperlongumine (PL), an alkaloid known to have anti-inflammatory and antioxidant effects, to play a neuroprotective role in 16-week-old female C57BL/6J mice treated with a common breast cancer regimen of doxorubicin, cyclophosphamide, and docetaxel (TAC). During social memory testing, TAC-treated mice exhibited impairment, while TAC/PL co-treated mice did not exhibit measurable social memory deficits. Proteomics analysis showed ERK1/2 signaling is involved in TAC and TAC/PL co-treatment. Reduced Nrf2 mRNA expression was also observed. mRNA levels of Gria2 were increased in TAC treated mice and reduced in TAC/PL co-treated mice. In this study, PL protects against social memory impairment when co-administered with TAC via multifactorial mechanisms involving oxidative stress and synaptic plasticity.     

晚期三阴性乳腺癌的药物治疗进展

三阴性乳腺癌为雌、孕激素受体及人表皮生长因子受体-2均为阴性的乳腺癌,由于缺乏特异性的治疗靶点,晚期治疗尚缺少有效的治疗方案。本文综述近年来晚期三阴性乳腺癌的药物治疗研究进展,主要包括化学治疗、靶向治疗、内分泌治疗、免疫治疗四个方面,旨在为临床治疗提供借鉴和参考。     

Aggregation-Induced Emission Luminogens for Mitochondria-Targeted Cancer Therapy

The importance of mitochondria in tumorigenesis makes these organelles an ideal target for cancer therapy. In recent years, luminogens with the aggregation-induced emission (AIE) effect have been developed for mitochondrial targeting and cancer treatment. The induction of mitochondrial dysfunction can be an effective pathway of chemotherapy, photodynamic therapy, and combination therapy against cancer. This review focuses on recent progress in the field of AIE luminogens (AIEgens) for cancer theranostics based on mitochondrial targeting and dysfunction. AIEgens for cancer treatment, including chemotherapy, photodynamic therapy, and combination therapy, are summarized herein. Molecular design efforts toward mitochondrial targeting and mitochondria-damaging mechanisms are also discussed. Finally, we discuss the challenges and future directions of development for AIEgens in mitochondria-targeted cancer treatment.     

Improved drug loading via spray drying of a chalcone implant for local treatment of cutaneous leishmaniasis

Current chemotherapy of cutaneous leishmaniasis (CL), even the mildest forms, encompasses multiple and painful injections with toxic drugs that cause systemic adverse effects. Recently, we showed the promising use of poly(lactic-co-glycolic acid) (PLGA) microparticles loaded with an antileishmanial nitrosylated chalcone (CH8) for effective, safe, local, and single-dose treatment of CL. Here, we proposed to optimize the delivery system by increasing the CH8 loading in PLGA-microparticles using spray drying instead of emulsification-solvent evaporation. The effect of solvent composition and polymeric matrix changes on thermal properties, loading efficiency, particle size, morphology, and spatial drug distribution of the CH8-loaded microparticles was evaluated. The results showed that spray drying allowed a higher CH8 content (18% w/w), as contrasting with the previous solvent evaporation technique that maximally incorporated 7.8% of CH8. In vitro studies on 96-hour incubation with L. amazonensis-infected macrophages showed that entrapment in spray-dried PLGA microparticles rendered CH8 safer, preserved its antileishmanial activity, and did not affect its antioxidant properties.     

Towards Light-Activated Ruthenium–Arene (RAPTA-Type) Prodrug Candidates

Cancer is currently one of the deadliest diseases worldwide. Based on the high incidence of this disease, the side effects associated with current chemotherapies and the appearance of drug resistance, considerable efforts have been directed towards the development of new anticancer drugs with new modes of action. Metal-based compounds are particularly attractive candidates due to their metabolic mechanisms, which differ substantially from those of organic drugs. Of special interest in this context are organometallic ruthenium(II) complexes of the type [Ru(η⁶-arene)(pta)Cl₂] (arene: p-cymene, toluene, benzene, etc.; pta: 1,3,5-triaza-7-phosphaadamantane), which are abbreviated to RAPTA. Complementary to chemotherapy, photoactivated chemotherapy is a technique that has received increasing attention towards the development of treatment for numerous kinds of cancer. With this in mind, a photoactive RAPTA-type complex bearing azide ligands has been designed. The diazide complex, [Ru(η⁶-p-cymene)pta-(N₃)₂], is inert in water, but slowly releases the azide ligand upon exposure to light. Consequently, the in vitro cytotoxicity of the complex in the dark and upon light exposure at λ=450 nm in human cervical carcinoma (HeLa) and noncancerous retinal pigment epithelium (RPE-1) cells was investigated. Although the cytotoxicity of the complex was found to be modest in the dark, an increase in toxicity upon light exposure was observed.     

多种口服升白药物治疗化疗相关白细胞减少症的实验研究

目的: 通过小鼠实验研究评价5种常用口服升白细胞药物治疗化疗相关白细胞减少症的疗效。方法: 采用环磷酰胺腹腔注射法制备小鼠化疗相关白细胞减少症模型,以瑞白为阳性对照药物,分别将5种口服升白细胞药物(芪胶升白胶囊、维血宁、复方皂矾丸、升白安和利可君)灌胃,用全血细胞分析仪测定血细胞计数,解剖小鼠并将其重要脏器称重,计算脏器指数。结果: 各组小鼠死亡率无明显差别。按照升白细胞计数的功效,从高到低依次为瑞白、利可君、升白安、维血宁、芪胶升白胶囊、复方皂矾丸,其中芪胶升白胶囊、复方皂矾丸升白细胞作用不明显;除此之外,升白安、利可君还可以提高红细胞计数、血红蛋白浓度及血小板计数。心、脾、肺3个脏器的脏器指数受较多的药物影响,就单种药物而言,升白安对脏器的影响最小,而复方皂矾丸影响的脏器最多。结论: 瑞白提升白细胞效果最佳,其次是利可君,升白安对血三系提升均有一定的作用,且对脏器的影响最小。     

Revisiting Hepatic Artery Infusion Chemotherapy in the Treatment of Advanced Hepatocellular Carcinoma

Hepatic artery infusion chemotherapy (HAIC) is a well-established and common treatment for advanced hepatocellular carcinoma (HCC), particularly in East Asia. However, HAIC is not recognized internationally. Although several trials have demonstrated the safety and efficacy of HAIC, evidence corroborating its overall survival (OS) benefits compared with standard treatments is insufficient. Nevertheless, HAIC may provide prominent benefits in selected patients such as patients with portal vein thrombosis or high intrahepatic tumor burden. Moreover, HAIC has been combined with several therapeutic agents and modalities, including interferon-alpha, multikinase inhibitors, radiation therapy, and immunotherapy, to augment its treatment efficacy. Most of these combinations appeared to increase overall response rates compared with HAIC alone, but results regarding OS are inconclusive. Two prospective randomized controlled trials comparing HAIC plus sorafenib with sorafenib alone have reported conflicting results, necessitating further research. As immunotherapy-based combinations became the mainstream treatments for advanced HCC, HAIC plus immunotherapy-based treatments also showed encouraging preliminary results. The trials of HAIC were heterogeneous in terms of patient selection, chemotherapy regimens and doses, HAIC combination agent selections, and HAIC technical protocols. These heterogeneities may contribute to differences in treatment efficacy, thus increasing the difficulty of interpreting trial results. We propose that future trials of HAIC standardize these key factors to reveal the clinical value of HAIC-based treatments for HCC.     

Blood–Brain Barrier in Brain Tumors: Biology and Clinical Relevance

The presence of barriers, such as the blood–brain barrier (BBB) and brain–tumor barrier (BTB), limits the penetration of antineoplastic drugs into the brain, resulting in poor response to treatments. Many techniques have been developed to overcome the presence of these barriers, including direct injections of substances by intranasal or intrathecal routes, chemical modification of drugs or constituents of BBB, inhibition of efflux pumps, physical disruption of BBB by radiofrequency electromagnetic radiation (EMP), laser-induced thermal therapy (LITT), focused ultrasounds (FUS) combined with microbubbles and convection enhanced delivery (CED). However, most of these strategies have been tested only in preclinical models or in phase 1–2 trials, and none of them have been approved for treatment of brain tumors yet. Concerning the treatment of brain metastases, many molecules have been developed in the last years with a better penetration across BBB (new generation tyrosine kinase inhibitors like osimertinib for non-small-cell lung carcinoma and neratinib/tucatinib for breast cancer), resulting in better progression-free survival and overall survival compared to older molecules. Promising studies concerning neural stem cells, CAR-T (chimeric antigen receptors) strategies and immunotherapy with checkpoint inhibitors are ongoing.     

Design of Biopolymer-Based Interstitial Therapies for the Treatment of Glioblastoma

Glioblastoma multiforme (GBM) is the most common form of primary brain cancer and has the highest morbidity rate and current treatments result in a bleak 5-year survival rate of 5.6%. Interstitial therapy is one option to increase survival. Drug delivery by interstitial therapy most commonly makes use of a polymer implant encapsulating a drug which releases as the polymer degrades. Interstitial therapy has been extensively studied as a treatment option for GBM as it provides several advantages over systemic administration of chemotherapeutics. Primarily, it can be applied behind the blood–brain barrier, increasing the number of possible chemotherapeutic candidates that can be used and reducing systemic levels of the therapy while concentrating it near the cancer source. With interstitial therapy, multiple drugs can be released locally into the brain at the site of resection as the polymer of the implant degrades, and the release profile of these drugs can be tailored to optimize combination therapy or maintain synergistic ratios. This can bypass the blood–brain barrier, alleviate systemic toxicity, and resolve drug resistance in the tumor. However, tailoring drug release requires appropriate consideration of the complex relationship between the drug, polymer, and formulation method. Drug physicochemical properties can result in intermolecular bonding with the polymeric matrix and affect drug distribution in the implant depending on the formulation method used. This review is focused on current works that have applied interstitial therapy towards GBM, discusses polymer and formulation methods, and provides design considerations for future implantable biodegradable materials.