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.

Multiresolution Finite Element Method Based on a New Locking-Free Rectangular Mindlin Plate Element

A locking-free rectangular Mindlin plate element with a new multi-resolution analysis (MRA) is proposed and a new finite element method is hence presented. The MRA framework is formulated out of a mutually nesting displacement subspace sequence whose basis functions are constructed of scaling and shifting on the element domain of basic full node shape function. The basic full node shape function is constructed by extending the split node shape function of a traditional Mindlin plate element to other three quadrants around the coordinate zero point. As a result, a new rational MRA concept together with the resolution level (RL) is constituted for the element. The traditional 4-node rectangular Mindlin plate element and method is a mono-resolution one and also a special case of the proposed element and method. The meshing for the monoresolution plate element model is based on the empiricism while the RL adjusting for the multiresolution is laid on the rigorous mathematical basis. The analysis clarity of a plate structure is actually determined by the RL, not by the mesh. Thus, the accuracy of a plate structural analysis is replaced by the clarity, the irrational MRA by the rational and the mesh model by the RL that is the discretized model by the integrated.

A RECTANGULAR SHELL ELEMENT FORMULATION WITH A NEW MULTI-RESOLUTION ANALYSIS

A multi-resolution rectangular shell element with membrane-bending based on the Kirchhoff-Love theory is proposed. The multi-resolution analysis （MRA） framework is formulated out of a mutually nesting displacement subspace sequence, whose basis functions are constructed of scaling and shifting on the element domain of basic node shape functions. The basic node shape functions are constructed from shifting to other three quadrants around a specific node of a basic element in one quadrant and joining the corresponding node shape functions of four elements at the specific node. The MRA endows the proposed element with the resolution level （RL） to adjust the element node number, thus modulating structural analysis accuracy accordingly. The node shape functions of Kronecker delta property make the treatment of element boundary condition quite convenient and enable the stiffness matrix and the loading column vectors of the proposed element to be automatically acquired through quadraturing around nodes in RL adjusting. As a result, the traditional 4-node rectangular shell element is a mono-resolution one and also a special case of the proposed element. The accuracy of a structural analysis is actually determined by the RL, not by the mesh. The simplicity and clarity of node shape function formulation with the Kronecker delta property, and the rational MRA enable the proposed element method to be implemented more rationally, easily and efficiently than the conventional mono-resolution rectangular shell element method or other corresponding MRA methods.