Bone tumor is a refractory neoplastic growth of tissue in bone. According to the unique environment and phys-chemical characteristics of bone tissues, the chemotherapeutic agents are unlikely to prolong the survival o...Bone tumor is a refractory neoplastic growth of tissue in bone. According to the unique environment and phys-chemical characteristics of bone tissues, the chemotherapeutic agents are unlikely to prolong the survival of patients and often associated with systemic side effects. The bone targeting drug delivery via systemic administration may provide both better treatment efficacy and less frequent administration. In this study, we describe the synthesis, in vitro and in vivo evaluation of novel melphalan-bisphosphonate hybrids, with a tumor microenvironment sensitive linkage, which could be enzymatic activation under tumor microenvironment conditions. We have also evaluated the in vitro targeting efficiency of these prodrugs via the affinity of hydroxyapatite （HA） and cellular proliferation. The in vivo distribution suggested the bisphosphonate conjugated prodrugs with high bone selectivity.展开更多
Immunotherapy techniques,such as immune checkpoint inhibitors,chimeric antigen receptor(CAR)T cell therapies and cancer vaccines,have been burgeoning with great success,particularly for specific cancer types.However,s...Immunotherapy techniques,such as immune checkpoint inhibitors,chimeric antigen receptor(CAR)T cell therapies and cancer vaccines,have been burgeoning with great success,particularly for specific cancer types.However,side effects with fatal risks,dysfunction in tumor microenvironment and low immune response rates remain the bottlenecks in immunotherapy.Nano metal-organic frameworks(nMOFs),with an accurate structure and a narrow size distribution,are emerging as a solution to these problems.In addition to their function of temporospatial delivery,a large library of their compositions,together with flexibility in chemical interaction and inherent immune efficacy,offers opportunities for various designs of nMOFs for immunotherapy.In this review,we overview state-of-the-art research on nMOFs-based immunotherapies as well as their combination with other therapies.We demonstrate that nMOFs are predominantly customized for vaccine delivery or tumor-microenvironment modulation.Finally,a prospect of nMOFs in cancer immunotherapy will be discussed.展开更多
基金financially supported by the National Natural Science Foundation of China (Nos. 31600811, 81573154, 81773432)the Application Fundamental Research Foundation of Sichuan Province Science and Technology Department, China (Nos. 2016JY0157, 2017JY0123)Scientific Research Foundation of the Health and Family Planning Commission of Sichuan Province, China (Nos. 17PJ556, 17PJ563)
文摘Bone tumor is a refractory neoplastic growth of tissue in bone. According to the unique environment and phys-chemical characteristics of bone tissues, the chemotherapeutic agents are unlikely to prolong the survival of patients and often associated with systemic side effects. The bone targeting drug delivery via systemic administration may provide both better treatment efficacy and less frequent administration. In this study, we describe the synthesis, in vitro and in vivo evaluation of novel melphalan-bisphosphonate hybrids, with a tumor microenvironment sensitive linkage, which could be enzymatic activation under tumor microenvironment conditions. We have also evaluated the in vitro targeting efficiency of these prodrugs via the affinity of hydroxyapatite （HA） and cellular proliferation. The in vivo distribution suggested the bisphosphonate conjugated prodrugs with high bone selectivity.
基金This work was supported by the National Natural Science Foundation of China(Nos.51773154,31771090,31971323 and 81871315)Shanghai Science and Technology Innovation(18JC1414500)N.W.would like to acknowledge supports from both Burapha and VISTEC.
文摘Immunotherapy techniques,such as immune checkpoint inhibitors,chimeric antigen receptor(CAR)T cell therapies and cancer vaccines,have been burgeoning with great success,particularly for specific cancer types.However,side effects with fatal risks,dysfunction in tumor microenvironment and low immune response rates remain the bottlenecks in immunotherapy.Nano metal-organic frameworks(nMOFs),with an accurate structure and a narrow size distribution,are emerging as a solution to these problems.In addition to their function of temporospatial delivery,a large library of their compositions,together with flexibility in chemical interaction and inherent immune efficacy,offers opportunities for various designs of nMOFs for immunotherapy.In this review,we overview state-of-the-art research on nMOFs-based immunotherapies as well as their combination with other therapies.We demonstrate that nMOFs are predominantly customized for vaccine delivery or tumor-microenvironment modulation.Finally,a prospect of nMOFs in cancer immunotherapy will be discussed.
