Previous studies have demonstrated that induction of reactive oxygen species (ROS) significantly enhances the cytotoxicity of paclitaxel (Ptx). Tetrandrine (Tet), a potent ROS inducer, synergistically enhances the antitumor effects of Ptx. To codeliver Ptx and Tet, which have low solubility, high systemic toxicity, and poor tumor selectivity, we designed a tumor microenvironment-activatable prodrug-based delivery system. A ROS-responsive prodrug was developed by the conjugation of Ptx to a biocompatible polymer (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol), DSPE-PEG) via the ROS-cleavable thioketal (TK) linker, which could self-assemble into core-shell nanoparticles with Tet in the inner core to form redox-responsive Ptx/Tet-coloaded nanoparticles (P/T-NPs). The synergistic anticancer mechanism of Ptx and Tet was systematically investigated by cytotoxicity assays, ROS detection, mitochondrial tracing, transmission electron microscopy, and both in vitro and in vivo experiments. Cell uptake of P/T-NPs increased in a time-dependent manner, with partial accumulation observed in the mitochondria. The targeted release of Tet in tumor sites with high ROS levels could further elevate intracellular ROS, which in turn accelerated the cleavage of the TK linker and promoted the release of Ptx, thereby enhancing its antitumor effect. P/T-NPs showed superior cytotoxicity, which is strongly correlated to the superior autophagy-inducing ability of P/T-NPs. Moreover, P/T-NPs effectively inhibit the tumor growth compared to either the free drug or their combination therapy. This study integrates tumor microenvironment activation, self-amplified drug release, and ROS-enhanced chemotherapy into a single nanoplatform, offering a promising strategy for targeted cancer therapy.

Ulcerative colitis (UC) is a diffuse chronic inflammation in the superficial intestine. Excessive accumulation of reactive oxygen species (ROS) leads to the of the colorectal damage. As the anti-inflammation therapy needs to be last for at least 3-5 years, the drugs demand less toxicity. However, current treatments in the clinic are often accompanied by unavoidable adverse side effects. Hydrogen is a nontoxic antioxidant reagent with excellent permeability of biomembranes, which shows the potential in treating UC. A novel simply designed hydrogen storage particle, Magnesium Hydride (MgH2) particle with an outer shell of passivated Magnesium oxide (MgO), was constructed in the current study to enable the safe and controlled release of hydrogen. This studies demonstrated that magnesium hydride particle (MgH2@MgO) was effective in scavenging excessive ROS, relieving the inflammation, and reversing the progression of UC through inhibiting the NF-κB signaling pathway, which provided the experimental evidence for the clinical prevention and therapy of UC.

The Naples prognostic score (NPS) is an effective inflammatory and nutritional scoring system widely applied as a prognostic factor in various cancers. We aimed to analyze the prognostic value of the NPS in patients diagnosed with non-small-cell lung cancer (NSCLC). We prospectively collected 395 patients diagnosed with NSCLC between January 2016 and December 2018 in two university-affiliated hospitals. Patients were divided into three groups according to their pretreatment NPS (Group 0: NPS = 0; Group 1: NPS = 1–2; Group 2: NPS = 3–4). Kaplan–Meier survival curves indicated that patients with higher NPS had a poorer overall survival (OS) and progress-free survival (PFS) (both P < 0.05). NPS was further confirmed as an independent prognostic factors of OS and PFS by multivariable survival analysis (both P < 0.05). Furthermore, stratifying by TNM stage, NPS also has significant predictive performance for OS and PFS in both early (I–IIIA) and advanced (IIIB–IV) stage NSCLC (all P < 0.05). The time-dependent receiver operating characteristic curve analysis demonstrated that NPS was more superior to other prognostic factors in predicting OS and PFS. In conclusion, NPS may serve as an effective indicator to predict OS and PFS in NSCLC patients regardless of TNM stage.

Purpose: To analyze the prognostic value of total, bioavailable and free 25-hydroxyvitamin D (25(OH)D) as well as vitamin D-binding protein (VDBP) in NSCLC patients. Methods: We prospectively collected and analyzed data for 395 patients diagnosed with NSCLC between January 2016 and December 2018 in two university-affiliated hospitals. Total and free 25(OH)D and VDBP were measured directly, and bioavailable 25(OH)D was calculated using a validated formula. Their prognostic values were evaluated by Cox proportional hazards model, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Results: Patients with NSCLC had significantly lower levels of total, bioavailable, and free 25(OH)D and higher VDBP levels in comparison to healthy controls (all P <0.001). In multivariate analyses, higher levels of total, bioavailable, and free 25(OH)D were independently associated better overall survival (OS) and progression-free survival (PFS). For OS, the adjusted HRs were 0.58 (95%CI, 0.40-0.87; P for trend=0.008), 0.45 (95%CI, 0.30-0.67; P for trend<0.001) and 0.49 (95%CI, 0.33-0.73; P for trend<0.001) for the highest versus lowest tertile of total, bioavailable and free 25(OH)D, respectively. The corresponding adjusted HRs for PFS were 0.61 (95%CI, 0.43-0.86; P for trend=0.006), 0.56 (95%CI, 0.40-0.80; P for trend=0.001) and 0.60 (95%CI, 0.42-0.85; P for trend=0.004), respectively. However, VDBP was not associated with either OS or PFS. Conclusion: The current study suggested that total, bioavailable and free 25(OH)D may be reliable prognosis indicators in NSCLC patients, though the optimal 25(OH)D form for NSCLC prognosis remains to be assessed in future studies.

Multiple myeloma (MM) is a second ranking hematological malignancy. Despite the fast advancement of new treatments such as bortezormib and daratumumab, MM patients remain incurable and tend to eventually become relapsed and drug‐resistant. Development of novel therapies capable of depleting MM cells is strongly needed. Here, daratumumab immunopolymersomes carrying vincristine sulfate (Dar‐IPs‐VCR) are reported for safe and high‐efficacy CD38‐targeted chemotherapy and depletion of orthotopic MM in vivo. Dar‐IPs‐VCR made by postmodification via strain‐promoted click reaction holds tailored antibody density (2.2, 4.4 to 8.7 Dar per IPs), superb stability, small size (43–49 nm), efficacious VCR loading, and glutathione‐responsive VCR release. Dar4.4‐IPs‐VCR induces exceptional anti‐MM activity with an IC50 of 76 × 10−12 m to CD38‐positive LP‐1 MM cells, 12‐ and 20‐fold enhancement over nontargeted Ps‐VCR and free VCR controls, respectively. Intriguingly, mice bearing orthotopic LP‐1‐Luc MM following four cycles of i.v. administration of Dar4.4‐IPs‐VCR at 0.25 mg VCR equiv. kg−1 reveal complete depletion of LP‐1‐Luc cells, superior survival rate to all controls, and no body weight loss. The bone and histological analyses indicate bare bone and organ damage. Dar‐IPs‐VCR appears as a safe and targeted treatment for CD38‐overexpressed hematological malignancies.

目的 基于炎症和营养指标探讨非小细胞肺癌(non-small-cell lung cancer,NSCLC)患者预后的影响因素建立预测总生存期(overall survival,OS)的列线图.方法 选取苏州肺癌生存队列2016年1月-2020年1月NSCLC患者371例,随机分为训练队列(n=278)和验证队列(n=93).在训练队列中,通过Cox比例风险模型确定独立危险因素,构建列线图.通过Bootstrap法和十折交叉验证对模型的性能进行评价.结果 训练队列和验证队列的1年生存率分别为83.8％和83.9％,2年生存率分别为65.1％和66.7％.最后纳入模型的变量为吸烟状况、分期、治疗方式、BMI、红细胞分布宽度(red cell distribution width,RDW)、中性粒细胞与淋巴细胞比值(neu-trophil-to-lymphocyte ratio,NLR)和白蛋白与球蛋白比值(albumin-to-globulin ratio,AGR)(均有P＜0.05).训练队列和验证队列的预测OS的C-index分别为0.824和0.762,模型十折交叉验证的平均准确率为77.3％,ROC曲线下面积(area under the curve,AUG)为0.885(95％ CI:0.751～1.000).结论 基于炎症和营养指标构建的列线图可以有效地预测NSCLC患者的总生存期.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although intensive chemotherapy greatly improved the survival rate, it is often accompanied by severe and lifelong side effects as a result of weak ALL selectivity. The intensive and poorly selective chemotherapy is also detrimental to patients' immune system. There is an urgent need to develop more selective and less toxic chemotherapy for ALL. Here, we report daratumumab-polymersome-vincristine (DP-VCR) as a CD38-directed nanotherapy for ALL. DP-VCR showed selective uptake in CD38-positive 697 and Nalm-6-Luc ALL cells and potent anti-ALL activity with an IC50 as low as 0.06 nM VCR, which was 13.7-fold more potent than free VCR. In contrast, no toxicity to human peripheral blood mononuclear cells was detected for DP-VCR even at 108.3 nM VCR. The apoptotic assays confirmed a high selectivity of DP-VCR to CD38-positive ALL cells. DP-VCR exhibited superior treatment of both 697 and Nalm-6-Luc orthotopic ALL models to all controls, as revealed by significant survival benefit and marked reduction of leukemia burden in bone marrow, blood, spleen, and liver. Importantly, DP-VCR induced few side effects. DP-VCR emerges as a safe and potent nanotherapy for CD38-positive ALL.

Purpose Elevated inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been identified as poor predictors of survival in several malignancies. This meta-analysis was performed to quantify the effect of pretreatment NLR and PLR on the survival of patients with endometrial cancer (EC). Methods This review systematically searched for relevant publications in databases of PubMed, Embase, and the Cochrane Library. Pooled hazard ratios (pHRs) with 95% confidence intervals (95% CIs) were determined and used to explore the association between inflammatory markers and overall survival (OS) and disease-free survival (DFS) in a random-effects model. Subgroup analysis, sensitivity analysis, and publication bias were also conducted in this meta-analysis. Results Nine articles comprising 3390 patients were included. NLR higher than the cutoff was associated with a shorter OS (pHR = 2.22, 95% CI 1.77–2.78) and poorer PFS (pHR = 1.81, 95% CI 1.35–2.41). Patients with elevated PLR had high risk of decreased OS (pHR = 1.99, 95% CI = 1.51–2.61) and unfavorable PFS (pHR = 2.02, 95% CI 1.45–2.80). Conclusions Elevated NLR and PLR during pretreatment are biomarkers of poor prognosis in patients with EC.

Paclitaxel (Ptx), a microtubule depolymerization inhibitor, is one of the first-line regimens in lung cancer chemotherapy. However, the poor solubility of Ptx, as well as hypersensitivity of the solvent Cremphor EL, severely limits its clinical application. Here we developed a drug-polymer conjugate of Ptx-SA-PEG, in which amphiphilic copolymers poly(ethylene glycol) (PEG) and Ptx were conjugated by succinic acid (SA). The Ptx-SA-PEG polymers self-assemble into nanoparticles (Ptx-NPs) for efficient delivery of Ptx; cell count kit-8 assay and clonogenic assay were used to analyze the antitumor effect of Ptx-NPs. Acridine orange/ethidium bromide double staining, apoptosis analysis and western blot were measured to explore the apoptotic cell death after Ptx-NPs or free Ptx treatment. Subcutaneous xenograft models were practiced to estimate its tumor cytotoxicity and nonspecific side effects in vivo. Immunohistochemistry was used to analyze the effects of apoptosis and proliferation in tumor tissue; in vitro studies demonstrated that Ptx-NPs treatment exhibited more tumor inhibitory activity compared with free Ptx, especially at the lower doses. Moreover, Ptx-NPs activated apoptotic proteins. Animal experiments showed Ptx-NPs induced less weight loss and organ damage than free Ptx. Moreover, tumor growth was slower after Ptx-NPs treatment, indicating the superior antitumor effect and slight side effect of Ptx-NPs over free Ptx. Conjugation of Ptx-SA-PEG provides a feasible way to acquire self-assembled supramolecular Ptx-loaded nanoparticles with higher drug loading efficiency, less non-specific toxicity and more stable and durable antitumor effect of Ptx, providing a potential strategy to meliorate its clinical therapeutic efficacy.

The Geriatric Nutritional Risk Index (GNRI) is widely applied as a prognostic factor in different cancers. We aimed to analyze the prognostic value of the GNRI in 257 patients diagnosed with advanced non-small-cell lung cancer (NSCLC). Patients with GNRI >98, 92-98, and <92 were grouped into normal, low risk and moderate/high risk groups, respectively. There were 45.1% patients at risk for malnutrition. Kaplan-Meier survival curves indicated that patients with lower GNRI scores had a poorer overall survival (OS). Two-year OS for normal, low risk and moderate/high risk groups were 57.4%, 42.3% and 15.8%, respectively. In multivariate survival analysis, GNRI (<92), body mass index (BMI, >= 24 kg/m2), combined therapy, hemoglobin and neutrophil-to-lymphocyte ratio (NLR) were independent prognostic factors of OS. Stratifying by age groups, GNRI (<92), hemoglobin and NLR were independent prognostic factors of OS in patients aged <65 years. GNRI (<92), smoking, BMI (>= 24 kg/m2) and platelet-to-lymphocyte ratio were independent prognostic factors of OS in patients aged >= 65 years. In conclusion, GNRI was a significant prognostic factor in advanced NSCLC patients regardless of age. A decreased GNRI may be considered as a clinical trigger for nutritional support in advanced NSCLC patients, though additional studies are still required to confirm the best cut-point.

Paclitaxel (Ptx), a type of microtubule depolymerization inhibitor, is one of the main components in gastric cancer chemotherapy. Some studies have demonstrated that tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has potential antitumor effects in several cancers. Aside from the direct anticancer effect, Tet is proved to synergistically enhance the antitumor effect of Ptx in gastric cancer. However, the application of the combinational strategy is limited by the poor solubility of both drugs. Nanodrug delivery systems including polymeric nanoparticles, self-assembled nanofibers, hydrogels, etc., hold the potential to meet the need. Here, a novel supramolecular nanomaterial, based on the concept of "carrier-free nanodrugs", is reported as a feasible platform for synergistic drug delivery. Ptx-SA-RGD is obtained through the conjugation of Ptx and the tumor-specific peptide RGD (arginine-glycine-aspartic acid) with succinic acid (SA) as a linker. Ptx-SA-RGD could self-assemble into Ptx nanofibers (P-NFs) with high drugloading efficiency. Tet was then encapsulated into P-NFs to acquire novel Ptx and Tet coloaded self-assembled nanofibers (P/T-NFs). The uptake study shows the dynamic internalization of P/T-NFs by the gastric cancer cell line MGC-803. P/T-NFs significantly triggered the accumulation of reactive oxygen species (ROS) in gastric cancer cells MGC803 and further decreased the mitochondrial membrane potential, which led to the induction of mitochondrial apoptosis with superior cytotoxicity against free drugs. Moreover, P/T-NFs suppressed the expressions of p-STAT3 and p-JAK, initiated cytochrome-C release, and promoted caspase protein expression. Furthermore, P/T-NFs demonstrated the strongest tumor-delaying effect as well as the lowest toxicity. Therefore, self-assembled nanofibers of P/T-NFs demonstrated an increase of the mitochondrial apoptosis level and a stronger antitumor effect both in vitro.and in vivo, which could be a potential way to enhance the clinical efficacy and reduce the side-effects of Ptx in gastric cancer.

Non-small cell lung cancer (NSCLC) is the most commonly diagnosed lung cancer and is associated with poor prognosis. This study aimed to analyze if serum C-reactive protein (CRP), albumin (Alb), and CRP/Alb ratio could provide prognostic information in patients with NSCLC. 387 patients with primary NSCLC were included in this analysis. Cox proportional hazards regression was used to estimate hazard ratio (HR) and 95% confidence interval (CI) of death with adjustment for some potential confounders. The multivariate regression analyses revealed the statistically significant associations of decreased survival of patients with NSCLC with elevated CRP, decreased Alb, and elevated CRP/Alb ratio. The HRs of mortality were 1.56 (95% CI: 0.80–3.04) and 2.64 (95% CI: 1.35–5.16) for patients in the second and the highest tertiles of CRP ( P -trend = 0.003). For albumin, the HR was 0.50 (95% CI: 0.29–0.85) for the normal group. The CRP/Alb ratio strongly predicted the survival of patients in the highest tertile with a fourfold risk of dying compared with those in the lowest tertile (HR = 4.14, 95% CI: 2.15–7.98). The subgroup analysis according to various patient characteristics confirmed these associations. In conclusion, serum CRP, albumin, and CRP/Alb ratio are predictive of survival for Chinese patients with NSCLC.

Background: To evaluate the efficacy and safety of liposome-paclitaxel (L-PTX)/L-PTX plus S-1 in advanced gastric cancer patients with poor performance status (PS). Methods: We performed this retrospective study on 17 advanced gastric cancer patients with poor PS [rated as >= 2 based on the Eastern Cooperative Oncology Group (ECOG) scale] who underwent the following chemotherapy regimen: (I) L-PTX single-agent: L-PTX 60-80 mg/m(2) given on days 1 and 8, in a 21-day cycle; (II) timed sequential (TS) regimen: L-PTX 60-80 mg/m(2) given on days 1 and 8. S-1, 40-60 mg/m(2) twice a day on days 1-14, in a 21-day cycle. Initially, some patients could not tolerate the 2-drug combination chemotherapy regimen, only L-PTX single-agent was given. After the patient's physical condition was improved, plus S-1 was also given. Results: A total of 17 patients were studied. No complete response (CR) or partial response (PR) were observed in six patients, accounting for 35.29% (6/17). Stable disease (SD) was observed in five patients, accounting for 29.41% (5/17), and progressive disease (PD) in 6, accounting for 35.29% (6/17). The objective response and disease control rates were 35.29% (6/17) and 64.71% (11/17), respectively. The median progression-free survival (PFS) and median overall survival (OS) were 6.50 months [95% confidence interval (CI): 4.81-8.20] and 13.00 months (95% CI: 0.00-33.65), respectively. The most common hematological toxicities were neutropenia and anemia. Conclusions: L-PTX/L-PTX plus S-1 in the treatment of advanced gastric cancer patients with poor PS can prolong the patients' PFS and OS, and the toxicity is tolerable.

Purpose: Non-small-cell lung cancer (NSCLC) is the most diagnosed lung cancer and is associated with poor prognosis. This study aimed to analyze whether fasting blood glucose (FBG) levels could provide prognostic information in Chinese patients with NSCLC, using the Suzhou Lung Cancer Survival study. Patients and methods: A prospective cohort study of adult patients with primary NSCLC was performed. The patients who were hospitalized between January 2016 and April 2018 in two hospitals affiliated with Soochow University were recruited. Patient information, including lifestyle habits and clinical and laboratory data, were collected through face-to-face interviews and evaluation of medical records. Follow-up was initiated from the date of patient enrollment until May 8, 2018 or until patient death. The long-term survival of patients was assessed every 6 months. Patient vital status was confirmed by using hospital records, telephone interview, or local death registration system. Cox proportional hazards regression was used to estimate hazard ratio and 95% confidence interval (CI) for death, with adjustment for cancer stage, medical treatments, smoking, and other potential confounders. Results: A total of 387 patients were included in the analysis, and the numbers (percentages) of patients with stages I, II, III, and IV NSCLC were 53 (13.7%), 41 (10.6%), 64 (16.5%), and 215 (55.6%), respectively. The median duration of follow-up was 19.1 months. Compared with patients in the second tertile of FBG, the HRs for mortality were 2.16 (95% CI: 1.26-3.73) and 1.87 (95% CI: 1.03-3.42) for those in the lowest one and diabetic group, respectively. Subgroup analysis according to various patient characteristics confirmed these associations. Conclusion: Diabetes and low FBG could be important predictors of death in patients with NSCLC. Maintaining appropriate blood glucose levels may improve prognosis in patients with NSCLC.

Numerous studies have explored the anti-tumor effect of berberine (BBR), but little clinical evidence guides the use of BBR in cancer patients. Our aim was to investigate the impact of BBR on various cancers in healthy animals to promote the transformation from bench to bed. PubMed, Embase, Springer, and Cochrane databases were searched from January 2000 to October 2018 for relevant articles. Only published studies focusing on the relationship between BBR and various cancers in vivo were qualified. Two review authors independently assessed the risk of bias for each study, and any disagreement was resolved by discussion or by involving a third assessor. A total of 26 studies from 2000 to 2018, focusing on various cancer types, including breast cancer, liver cancer, colorectal cancer, nasopharyngeal carcinoma, lung cancer, gastric cancer, neuroepithelial cancer, endometrial carcinoma, esophageal cancer, tongue cancer, cholangiocarcinoma, and sarcoma were included. Overall, BBR reduced tumor volume (SMD =3.72, 95% CI: 2.89, 4.56, Z = 8.73, p < 0.00001) and tumor weight (SMD =2.35, 95% CI: 1.51, 3.19, Z = 5.50, p < 0.00001) in a linear The dose–response relationship (Pearson r = − 0.6717, p < 0.0001 in tumor volume analysis; Pearson r = − 0.7704, p < 0.0005 in tumor weight analysis). BBR inhibited angiogenesis in tumor tissues (SMD = 4.29, 95% CI: 2.14, 6.44, Z = 3.92, p < 0.00001), but it had no significant effect on the body weight of experimental animals (SMD = 0.11, 95% CI: − 0.70, 0.92, Z = 0.27, p = 0.78). Publication bias was not detected. BBR exerted anti-tumor effects in a variety of tumors in vivo, especially breast cancer and lung cancer, and the evidence was still insufficient in colorectal cancer and gastric cancer.

Background: Numerous studies have reported contradicting results on the relationship between cancer mortality and schizophrenia. Our aim is to quantify the mortality rate of common site-specific cancers among patients with schizophrenia and to synthesize the available research evidence. Method: We performed a systemic search of the PubMed, EMBASE and Web of Science databases. Studies reporting the mortality rate of different cancer in patients with schizophrenia were included. A random-effects model was applied to calculate the pooled relative risks (RRs) with 95% confidence intervals (95%CIs). Results: Seven studies consisting of a total of 1,162,971 participants with schizophrenia were included in this meta-analysis. Data regarding mortality risk of breast, colon, lung and prostate cancer among schizophrenia patients were subjected to quantitative analysis. Pooled results showed significant increases in mortality risk of breast cancer (RR = 1.97, 95%CI 1.38–2.83), lung cancer (RR = 1.93, 95%CI 1.46–2.54) and colon cancer (RR = 1.69, 95%CI 1.60–1.80) in patients with schizophrenia compared with those in the general population or control group. The mortality risk of prostate cancer increased in male patients, although no significant difference was detected (RR = 1.58, 95% CI 0.79–3.15). Increased risks of mortality from lung and colon cancer were observed in female patients (RR = 2.49, 95%CI 2.40–2.59 and RR = 2.42, 95%CI 1.39–4.22, respectively) and elevated risks of mortality from lung and colon cancer in male patients (RR = 2.40, 95%CI 2.30–2.50 and RR = 1.90, 95%CI 1.71–2.11, respectively) were detected. Conclusions: Individuals with schizophrenia have a significantly high risk of mortality from breast, colon, and lung cancer.

Paclitaxel (Ptx) is a first-line chemotherapeutic drug for advanced gastric cancer. However, the poor solubility of Ptx still limits its clinical application. Here, we designed a methoxy poly(ethylene glycol)/poly(epsilon-caprolactone) (DSPE-PEG2000-TK-Ptx) nanoparticle loaded with "ROS sensitive" groups—thioketal (TK) to improve Ptx release in high ROS areas in cells. We evaluated the anticancer effect of the DSPE-PEG2000-TK-Ptx nanoparticles (Ptx-NPs) in the SGC-7901 gastric tumor cell line. The Ptx-NPs-treated group showed superior cytotoxicity to the same dose of free Ptx by MTT test and clonogenic assay. Autophagy inhibitor 3-MA protected cells from the cytotoxicity of Ptx in tumor cells. More autophagic cells were identified in the Ptx-NPs group via MDC/EB dual staining. NAC, an ROS inhibitor, inhibited cell autophagy induced by free Ptx or Ptx-NPs. SGC-7901 cells transfected with mCherry-EGFP-LC3II showed much brighter fluorescence in the Ptx-NPs group, while 3-MA markedly suppressed the fluorescence. Western blot verified the protein expression of autophagy, such as P62, Beclin 1 and LC3II. In this study, "ROS sensitive" conjugated DSPE-PEG2000-TK-Ptx nanoparticles with enhanced cancer-suppressive efficacy were produced. Ptx-NPs could be a promising antitumor agent for gastric cancer treatment with more efficiency and fewer side effects.

Chemotherapy is widely used in the clinic though its benefits are controversial owing to low cancer specificity. Nanovehicles capable of selectively transporting drugs to cancer cells have been energetically pursued to remodel cancer treatment. However, no active targeting nanomedicines have succeeded in clinical translation to date, partly due to either modest targetability or complex fabrication. CD44-specific A6 short peptide (KPSSPPEE) functionalized polymersomal epirubicin (A6-PS-EPI), which boosts targetability and anticancer efficacy toward human multiple myeloma (MM) in vivo, is described. A6-PS-EPI encapsulating 11 wt% EPI is small (≈55 nm), robust, reduction-responsive, and easy to fabricate. Of note, A6 decoration markedly augments the uptake and anticancer activity of PS-EPI in CD44-overexpressing LP-1 MM cells. A6-PS-EPI displays remarkable targeting ability to orthotopic LP-1 MM, causing depleted bone damage and striking survival benefits compared to nontargeted PS-EPI. Overall, A6-PS-EPI, as a simple and intelligent nanotherapeutic, demonstrates high potential for clinical translation.

Paclitaxel (Ptx) has been recommended as one of the main components of first-line chemotherapy for gastric cancer. However, the side effects of Ptx have greatly limited its clinical application because of its poor solubility and emerging resistance. In the current study, we designed novel self-assembled Ptx nanofibers with extremely high drug loading efficiency through conjugation of Ptx with succinic acid (sa), resulting in self-assembled nanofibers without the need for additional polymeric carriers. Cytotoxicity tests showed the superior effect of Ptx-sa against the gastric cancer cell lines SCG7901 and BGC823, but there was an obvious discrepancy between the number of apoptotic cells and dead cells, which indicates that other mechanisms may be involved in Ptx-sa-induced cell death. Mechanism studies, including apoptosis and autophagy detection, showed that Ptx-sa induced apoptosis and autophagy-induced cell death more efficiently than an equivalent dose of free Ptx. Most importantly, based on TEM and transfection with dual fluorescencelabeled LC3, more autophagosomes and increased autophagic flux were elicited by Ptx-sa in gastric cancer cells than an equivalent dose of free Ptx. Western blotting demonstrated that Ptx-sa induced the expression of LC3 II, a marker of autophagy, much more effectively than free Ptx. Moreover, an in vivo study demonstrated that Ptx-sa nanofibers significantly enhanced the anti-cancer effect of Ptx. Therefore, the self-assembled Ptx-sa nanofibers may exert cytotoxicity by inducing both apoptosis and autophagic cell death and thus might be a promising strategy to strengthen the therapeutic efficacy of Ptx in gastric cancer.