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.

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.

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.