Metal-Organic Framework Nanocarriers for Drug Delivery in Biomedical Applications

Investigation of metal–organic frameworks(MOFs)for biomedical applications has attracted much attention in recent years.MOFs are regarded as a promising class of nanocarriers for drug delivery owing to well-defined structure,ultrahigh surface area and porosity,tunable pore size,and easy chemical functionalization.In this review,the unique properties of MOFs and their advantages as nanocarriers for drug delivery in biomedical applications were discussed in the first section.Then,state-ofthe-art strategies to functionalize MOFs with therapeutic agents were summarized,including surface adsorption,pore encapsulation,covalent binding,and functional molecules as building blocks.In the third section,the most recent biological applications of MOFs for intracellular delivery of drugs,proteins,and nucleic acids,especially aptamers,were presented.Finally,challenges and prospects were comprehensively discussed to provide context for future development of MOFs as efficient drug delivery systems.

XELOX doublet regimen versus EOX triplet regimen as first-line treatment for advanced gastric cancer:An open-labeled,multicenter,randomized,prospective phase III trial(EXELOX)

Background:There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer(AGC).We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine(XELOX)and epirubicin,oxaliplatin,plus capecitabine(EOX)regimens in treating AGC.Methods:This phase III trial enrolled previously untreated patients with AGC whowere randomly assigned to receive the XELOXor EOXregimen.The primary endpoint was non-inferiority in progression-free survival(PFS)for XELOX as compared with EOX on an intention-to-treat basis.Results:Between April 10,2015 andAugust 20,2020,448AGCpatientswere randomized to receive XELOX(n=222)or EOX(n=226).The median PFS(mPFS)was 5.0 months(95%confidence interval[CI]=4.5-6.0 months)in the XELOX arm and 5.5 months(95%CI=5.0-6.0 months)in the EOX arm(hazard ratio[HR]=0.989,95%CI=0.812-1.203;P_(non-inferiority)=0.003).There was no significant difference inmedian overall survival(mOS)(12.0 vs.12.0months,P=0.384)or objective response rate(37.4%vs.45.1%,P=0.291)between the two groups.In patients with poorly differentiated adenocarcinoma and liver metastasis,the EOX arm had a significantly longer mOS(P=0.021)and a trend of longer mPFS(P=0.073)than the XELOX arm.The rate of grade 3/4 adverse events(AEs)was 42.2%(90/213)in the XELOX arm and 72.5%(156/215)in the EOX arm(P=0.001).The global health-related quality of life(QoL)score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy.Conclusions:This non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients.However,the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.

The Chinese Society of Clinical Oncology(CSCO)clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma

Nasopharyngeal carcinoma(NPC)is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa.To develop these comprehensive guidelines for the diagnosis and management of NPC,the Chinese Society of Clinical Oncology(CSCO)arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write,discuss,and revise the guidelines.Based on the findings of evidencebased medicine in China and abroad,domestic experts have iteratively developed these guidelines to provide proper management of NPC.Overall,the guidelines describe the screening,clinical and pathological diagnosis,staging and risk assessment,therapies,and follow-up of NPC,which aim to improve the management of NPC.

TIGER:A Web Portal of Tumor Immunotherapy Gene Expression Resource

Immunotherapy is a promising cancer treatment method;however,only a few patients benefit from it.The development of new immunotherapy strategies and effective biomarkers of response and resistance is urgently needed.Recently,high-throughput bulk and single-cell gene expression profling technologies have generated valuable resources.However,these resources are not well organized and systematic analysis is difficult.Here,we present TIGER,a tumor immunotherapy gene expression resource,which contains bulk transcriptome data of 1508 tumor samples with clinical immunotherapy outcomes and 11,057 tumor/normal samples without clinical immunotherapy outcomes,as well as single-cell transcriptome data of 2,116,945 immune cells from 655 samples.TIGER provides many useful modules for analyzing collected and user-provided data.Using the resource in TIGER,we identified a tumor-enriched subset of CD4^(+)T cells.Patients with melanoma with a higher signature score of this subset have a significantly better response and survival under immunotherapy.We believe that TIGER will be helpful in understanding anti-tumor immunity mechanisms and discovering effective biomarkers.

Progress in the mechanism of radiation-induced lung injury

Radiation therapy is widely used to treat various thoracic tumors.However,X-rays inevitably cause damage to normal lung tissues while killing tumor cells,leading to the occurrence of radiation-induced lung injury(RILI).Recent data showed that lung cancer has the highest incidence of RILI(5-25%),followed by mediastinal lymphoma(5-10%),and breast cancer(1-5%).®With the progress in research,our understanding of the mechanism of RILI has changed from the traditional hypothesis of“target cell death”to“a continuous process involving multiple cells,”which is dynamic and evolving[Figure 1],In the present review,we summarize the current knowledge of RILI,and discuss the potential limitations of combined radio-immunotherapy.

Disulfide-Containing Molecular Sticker Assists Cellular Delivery of DNA Nanoassemblies by Bypassing Endocytosis

The delivery efficiency of DNA nanoassemblies to the cytosol remains unsatisfactory due to endoand lysosomal entrapment and degradation,which restricts their bioanalytical and biomedical applications.Herein,the authors developed a disulfide-containing molecular sticker(DSMS)assisted approach to achieve efficient cytosolic delivery of DNA nanoassemblies.DSMS is designed to consist of a disulfide unit for thiol-mediated uptake and a guanidinium cation unit for strongly adhering to DNA nanoassemblies.After attaching with DSMS,a set of DNA nanoassemblies maintained their original three-dimensional features but had a different cellular internalization pathway.These results demonstrated that DSMS-DNA nanoassemblies complex did not enter the cells via endocytosis but instead entered through thiol-mediated direct uptake.Taking advantages of this facile assembly,universal applicability,and direct cytosolic delivery,DSMS might serve as a potent agent to facilitate the applications of DNA nanoassemblies in a variety of fields,such as bioimaging,drug delivery,and gene therapy.

CACA guidelines for holistic integrative management of nasopharyngeal carcinoma

Purpose Nasopharyngeal carcinoma(NPC)is a malignant epithelial tumor originating in the nasopharynx and is particularly prevalent in southern China.Unfortunately,international guidelines,such as NCCN or ESMO,fail to adequately coincide with clinical practice in China,making it difficult to achieve precision personalized therapy in China.The aim of this guideline is to better promote a"Multidisciplinary Team to Holistic Integrative Medicine"(MDT to HIM)system for the prevention,screening,diagnosis,treatment,and rehabilitation of NPC.Methods The China Anti-Cancer Association(CACA)invited domestic multi-disciplinary experts,involving radiologists,oncologists,surgeons,pathologists,herbalists,physiatrists,and psychologists,to write,discuss,and revise the guidelines.Based on the integration of research evidence,clinical experience,and patient needs,the domestic experts have iteratively developed these guidelines to provide proper and feasible management of NPC.Results and conclusion The CACA Guidelines for Holistic Integrative Management of Nasopharyngeal Carcinoma are more suitable for China’s clinical practice,highlight Chinese characteristics,and have important clinical significance.