Application of Nano-Delivery Systems in Lymph Nodes for Tumor Immunotherapy

Immunotherapy has become a promising research“hotspot”in cancer treatment.“Soldier”immune cells are not uniform throughout the body;they accumulate mostly in the immune organs such as the spleen and lymph nodes(LNs),etc.The unique structure of LNs provides the microenvironment suitable for the survival,activation,and proliferation of multiple types of immune cells.LNs play an important role in both the initiation of adaptive immunity and the generation of durable anti-tumor responses.Antigens taken up by antigen-presenting cells in peripheral tissues need to migrate with lymphatic fluid to LNs to activate the lymphocytes therein.Meanwhile,the accumulation and retaining of many immune functional compounds in LNs enhance their efficacy significantly.Therefore,LNs have become a key target for tumor immunotherapy.Unfortunately,the nonspecific distribution of the immune drugs in vivo greatly limits the activation and proliferation of immune cells,which leads to unsatisfactory anti-tumor effects.The efficient nano-delivery system to LNs is an effective strategy to maximize the efficacy of immune drugs.Nano-delivery systems have shown beneficial in improving biodistribution and enhancing accumulation in lymphoid tissues,exhibiting powerful and promising prospects for achieving effective delivery to LNs.Herein,the physiological structure and the delivery barriers of LNs were summarized and the factors affecting LNs accumulation were discussed thoroughly.Moreover,developments in nano-delivery systems were reviewed and the transformation prospects of LNs targeting nanocarriers were summarized and discussed.

BIOPOLYMER BASED NANO-DELIVERY SYSTEMS FOR ENHANCING BIOAVAILABILITY OF NUTRACEUTICALS

Recently, there has been an increasing interest in the development of efficient food-grade oral nano-delivery systems for encapsulation, protection and target delivery of nutraceuticals to enhance their bioavailability, fiarther to prevent disease and promote human health and well-being. Food proteins represent promising candidates for efficient nutraceutical nanocarriers due to their exceptional characteristics, namely biodegradability, nonantigenicity, high nutritional value, abundant renewable sources and extraordinary binding capacity to various nutraceuticals. In addition, their biocompatibility, biodegradability, low toxicity, low cost, and non-starch polysaccharides possess many favourable characteristics such as stability in the harsh gastric environment, resistance to digestive enzymes, and mucoadhesiveness to intestinal mucosal surface. This review describes the design and formation of nanoscaled delivery systems for nutraceuticals using food-grade proteins （including peptides）, polysaccharides and their associative complexes. The toxicity and cellular uptake fate of the nanostructures, as well as their effects on the intestinal absorption of the encapsulated nutraceuticals were also discussed.

Applications and developments of gene therapy drug delivery systems for genetic diseases

Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity.Currently,gene therapy drugs such as siRNA,shRNA,antisense oligonucleotide,CRISPR/Cas9 system,plasmid DNA and miRNA have shown great potential in biomedical applications.To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues,cells and organelles,the development of excellent drug delivery vehicles is of utmost importance.Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression.With the development of nanotechnology,novel nanocarriers are gradually replacing viral vectors,emerging superior performance.This review mainly illuminates the current widely used gene therapy drugs,summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs,and sums up the application of gene therapy to treat genetic diseases.Additionally,the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system.

Toosendanin:upgrade of an old agent in cancer treatment

Toosendanin(TSN),a tetracyclic triterpenoid derived from Melia toosendan and M.azedarach,demonstrates broad application prospects in cancer treatment.Although previously employed as a pesticide,recent studies have revealed its potential therapeutic value in treating various types of cancer.TSN exerts an anticancer effect via mechanisms including proliferation inhibition,apoptosis induction,migration suppression,and angiogenesis inhibition.However,TSN's toxicity,particularly its hepatotoxicity,significantly limits its therapeutic application.This review explored the dual nature of TSN,evaluating both its anticancer potential and toxicological risks,emphasizing the importance of balancing these aspects in therapeutic applications.Furthermore,we investigated the incorporation of TSN into novel therapeutic strategies,such as Proteolysis-targeting chimeras(PROTAC)technology and nanotechnology-based drug delivery systems(DDS),which enhance treatment efficacy while mitigating toxicity in normal tissues.

An AIE Star Polymer with Enhanced Co-Delivery of Drug and Gene for Synergistic Pest Control

Pesticides,as the most common means of pest managements,have caused a series of problems such as pest resistance and environmental pollution.Aggregation-induced emission(AIE)polymers exhibit great potential in biological applications because their fluorescent intensities significantly enhance in the aggregated state.In this paper,an AIE star polymer including a tetraphenyl ethylene(TPE)core and poly(2-(dimethylamino)ethyl methacrylate)arms is designed and further developed as a multi-functional nanocarrier for agricultural pest control.The nanocarrier shows high water solubility,good size stability and AIE imaging ability.Meanwhile,the twisted AIE core and positively charged polymer arms make the nanocarrier efficiently co-load dinotefuran(DIN)and dsRNA via hydrogen bonds and electrostatic interactions,respectively.The AIE star polymer displays low toxicity and high fluorescence traceability.As a result,the nanocarrier co-loading with DIN and dsRNA exhibits a highly synergistic insecticidal effect with higher pest mortality compared to the separate delivery of DIN and dsRNA.This study develops the AIE star polymer to improve the efficiency of co-delivery of drug and dsRNA and proposes a new strategy toward efficient and synergistic pest control.

Nanomedicine for tumor therapy-current status and challenges

The field of nanomedicine in controlled drug delivery systems, especially for tumor targeting, has tremendously progressed over the past decades because of its plentiful benefits, such as biocompatibility, stability in blood circulation, and ability to reduce side effects. Although a large number of relevant papers are published every year, few nanodrugs are available for clinical treatment. The present review aimed to explore the barriers in nanomedicine delivery and tumor targeting. Rational design of nanomedicine should consider not only tumor heterogeneity, in vivo metabolism, and physicochemical properties, but also more efficient innovations in particulate formulations for clinical application.