A multi-functional nanoplatform for efficacy tumor theranostic applications

Nanomaterials with multiple functions have become more and more popular in the domain of cancer research. MoS2 has a great potential in photothermal therapy, X-ray/CT imaging and drug delivery. In this study, a water soluble MoS2 nanosystem(MoS2-PEG) was synthesized and explored in drug delivery, photothermal therapy(PTT) and X-ray imaging.Doxorubicin(DOX) was loaded onto MoS2-PEG with a high drug loading efficiency(~69%)and obtained a multifunctional drug delivery system(MoS2-PEG/DOX). As the drug delivery, MoS2-PEG/DOX could efficiently cross the cell membranes, and escape from the endosome via NIR light irradiation, lead to more apoptosis in MCF-7 cells, and afford higher antitumor efficacy without obvious toxic effects to normal organs owing to its prolonged blood circulation and 11.6-fold higher DTX uptake of tumor than DOX. Besides, MoS2-PEG/DOX not only served as a drug delivery system, but also as a powerful PTT agent for thermal ablation of tumor and a strong X-ray contrast agent for tumor diagnosis. In the in vitro and in vivo studies, MoS2-PEG/DOX exhibited excellent tumor-targeting efficacy, outstanding synergistic anti-cancer effect of photothermal and chemotherapy and X-ray imaging property,demonstrating that MoS2-PEG/DOX had a great potential for simultaneous diagnosis and photothermal-chemotherapy in cancer treatment.

Estimation of Potato Biomass and Yield Based on Machine Learning from Hyperspectral Remote Sensing Data

The estimation of potato biomass and yield can optimize the planting pattern and tap the production potential.Based on partial least square(PLSR),multiple linear regression(MLR),support vector machine(SVM),random forest(RF),BP neural network and other machine learning algorithms,the biomass estimation model of potato in different growth stages is constructed by using single variables such as original spectrum,first-order differential spectrum,combined spectrum index and vegetation index(VI)and their coupled combination variables.The accuracy of the models is compared and analyzed,and the best modeling method of biomass in different growth stages is selected.Based on the optimized modeling method,the biomass of each growth stage is estimated,and the yield estimation model of different growth stages is constructed based on the estimation results and the linear regression analysis method,and the accuracy of the model is verified.The results showed that in tuber formation stage,starch accumulation stage and maturity stage,the biomass estimation accuracy based on combination variable was the highest,the best modeling method was MLR and SVM,in tuber growth stage,the best modeling method was MLR,the effect of yield estimation is good.It provides a reference for the algorithm selection of crop biomass and yield models based on machine learning.

Advances of nanoparticles as drug delivery systems for disease diagnosis and treatment

Decades have passed since the first nanoparticles-base medicine was approved for human cancer treatment, and the research and development of nanoparticles for drug delivery are always undergoing.Nowadays, the significant advances complicate nanoparticles’ branches, including liposomes, solid lipid nanoparticles, inorganic nanoparticles, micelles, nanovaccines and nano-antibodies, etc. These nanoparticles show numerous capabilities in treatment and diagnosis of stubborn diseases like cancer and neurodegenerative diseases, emerging as novel drug carriers or therapeutic agents in future. In this review, the complicated branches of nanoparticles are classified and summarized, with their property and functions concluded. Besides, there are also some delivery strategies that make nanoparticles smarter and more efficient in drug delivery, and frontiers in these strategies are also summarized in this review. Except these excellent works in newly-produced drug delivery nanoparticles, some points of view and future expectations are made in the end.

Carrier-free programmed spherical nucleic acid for effective ischemic stroke therapy via self-delivery antisense oligonucleotide

Antisense oligonucleotide(ASO)for anti-apoptosis is emerging as a highly promising therapeutic agents for ischemic stroke with complex pathological environment.However,its therapeutic efficacy is seriously limited by a number of challenges including inefficient internalization,low blood-brain barrier(BBB)penetration,poor stability,and potential toxicity of the carrier.Herein,a carrier-free programmed spherical nucleic acid nanostructure is developed for effective ischemic stroke therapy via integrating multifunctional modules into one DNA structure.By co-encoding caspase-3-ASO and transferrin receptor(TfR)aptamer into circle template,the spherical nucleic acid nanostructure(TD)was obtained via self-assembly.The experimental results demonstrated that the developed TD displayed efficient BBB penetration capability(6.4 times)and satisfactory caspase-3 silence effect(2.3 times)due to the dense DNA packaging in TD.Taken together,our study demonstrated that the carrier-free programmed spherical nucleic acid nanostructure could significantly improve the therapeutic efficacy of ischemic stroke and was a promising therapeutic tool for various brain damage-related diseases.

Hydrogel-mediated drug delivery for treating stroke

Stroke is a common disease and is the major cause of death and disability.It occurs and generates devastating neurological deficits when cerebral blood vessel is blocked(ischemic stroke,IS)or ruptured(hemorrhagic stroke,HS).Hydrogel,being biodegradable and biocompatible,have shown attractive advantages in stroke therapy as a new biomaterial with desirable mechanical properties and tunability of structure,owing to special ability to load different cargoes for multiple treatment strategies,such as pharmacotherapy based on drug-delivery systems and cell therapy including mesenchymal stem cells(MSCs)and neural progenitor cells(NPCs)for improving functional outcomes.However,a comprehensive review of the functional hydrogel for treatment of stroke is still lacking.Therefore,in this work,the main pathological mechanisms of stroke including IS and HS are comprehensively described.The benefits of hydrogel for stroke treatment are also summarized regarding the natural advantages and the delivery advantages.Simultaneously,the application development of hydrogel for treatment of stroke is highlighted.Finally,the unique considerations and challenges in the design and application of hydrogel is discussed for treatment of stroke and clinical application in the future.

Recent Progress on High-Z Metal-Based Nanomaterials for Cancer Radiosensitization

Radiotherapy is a mainstay treatment for malignant tumors in clinical practice.However,enhancing radiation damage to tumor cells meanwhile sparing normal tissues is still a great challenge in radiotherapy.Nanomaterials with high atomic number(Z)values are promising radiosensitizers by promoting the radiation energy deposition in irradiated tumor cells,thus enhancing the therapeutic ratio of radiotherapy.In this review,we described the mechanisms of high-Z element based-radiosensitizers and systematically summarized the recent progress on high-Z metal-based nanomaterials,including high-Z metal-based nanoparticles,high-Z metal-based nanoscale metal-organic frameworks and high-Z metal-doping nanomaterials.Finally,further potential and challenges in this field were discussed.

Boosting 5-ALA-based photodynamic therapy by a liposomal nanomedicine through intracellular iron ion regulation

5-Aminolevulinic acid(5-ALA)has been approved for clinical photodynamic therapy(PDT)due to its negligible photosensitive toxicity.However,the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells.Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair,a liposomal nanomedicine(MFLs@5-ALA/DFO)with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA,which was prepared by co-encapsulating 5-ALA and DFO(deferoxamine,a special iron chelator)into the membrane fusion liposomes(MFLs).MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery.MFLs@5-ALA/DFO could efficiently reduce iron ion,thus blocking the biotransformation of photosensitive protoporphyrin IX(Pp IX)to heme,realizing significant accumulation of photosensitivity.Meanwhile,the activity of DNA repair enzyme was also inhibited with the reduction of iron ion,resulting in the aggravated DNA damage in tumor cells.Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA.

Y-Shaped Circular Aptamer–DNAzyme Conjugates for Highly Efficient in Vivo Gene Silencing

Oligonucleotide drugs have been used widely as therapeutic agents for gene therapy,while their instability in biological media and inefficiency for intracellular delivery remain major hurdles for practical in vivo applications.Herein,we report a circular Y-shaped aptamer–DNAzyme conjugate(cYAD)for highly efficient in vivo gene silencing via RNA cleavage,which can been employed in various disease treatments,including cancer,inflammation,as well as viral infections.Systematic studies revealed that cyclization of the DNA structure could improve the stability of oligonucleotide drugs in vivo.Besides,the bivalent aptamer motifs provided a specific and enhanced tumor cell targeting ability for accumulation and retention of the oligonucleotide drugs at the tumor site.As a proof of concept,a widely applicable Na+-dependent fluorescent sensor,NaA43 DNAzyme,was used to inhibit MET gene expression in mice tumor model tissues,which exhibited highly efficient gene silencing performance in vivo,which confirmed our findings with cYAD.This strategy provides a novel approach for the construction of oligonucleotide drugs for practical therapeutic applications.