According to the World Health Organization (WHO), cancer has become one of the world's largest causes of death. As the main means of treating cancer, chemotherapy has great toxic side effects due to lack of tumor selectivity. Harnessing innate immunity is an appealing therapeutic strategy for the treatment of cancers. Innate immunity is a natural defense system formed by the body during growth and development. So far, a number of strategies have been developed to specifically kill cancer based on the innate immune system, among which therapeutic antibodies and chimeric antigen receptor (CAR)-engineered natural killer (NK) cells or macrophages are most important. Despite their remarkable success, they are associated with technical hurdles, and the use of antibodies and CAR engineering may induce some adverse side effects, such as fever, nausea, vomiting, allergies, etc. Therefore, there is an urgent need to develop a relatively safe new method to specifically amplify innate immune killing against cancers.
Scheme 1. Schematic illustration of redirecting the innate cell killing against TNBC via MINBs.
In view of this, Prof. Zhen Liu’s group has developed a novel biomimetic molecular recognition-based cancer immunotherapy strategy, on the base of their previous development of reverse microemulsion-confined epitope-oriented surface imprinting and cladding (ROSIC) (Adv. Sci.2021, 8, 2101713; Sci. Bull.2022, 67, 278-287)and the applications of molecularly imprinted polymers in cancer therapy (Angew.Chem. Int. Ed. 2019,58: 10621; Angew.Chem.int. Ed. 2021,60,2663-2667; ACS Nano, 2021, 15, 11, 18214–18225;Small 2022, n/a, 2201671; Chem. Sci. 2022, 13, 10897-10903). This study developed a new strategy called molecularly imprinted nanobeacons (MINBs) for redirecting innate immune killing cells towards to efficiently kill cancer cells. Using refractory triple-negative breast cancer (TNBC) as a cancer model, the study synthesized recognizable molecularly imprinted nanoparticles (nanoMIP) targeting the biomarker non-metastatic melanoma glycoprotein B (GPNMB). Then the hapten fluorescein (FITC) were modified on the surface of the particle, which can be recognized and bound by its specific antibody. The MINBs could tag the TNBC cells via binding with GPNMB and thereby provide navigation for recruiting hapten-specific antibodies. The gathered antibodies could further bind Fc-gamma receptors expressed on natural killer cells and macrophages, triggering specific antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) to efficiently kill the tagged cancer cells (Scheme 1).The effective elimination of TNBC was achieved by the MINBs without any drugs. Moreover, the nanoplatform could be extended to other targets to develop immunotherapy for other diseases.
This research was published online in Angew. Chem. Int. Ed. Prof. Zhen Liu is the corresponding author, Ph.D. candidates Peixin Guan are the first authors. This work was funded by the Key Grant (21834003) and the Excellent Research Program of Nanjing University (ZYJH004).
Online link:
Molecularly Imprinted Nanobeacons Redirect Innate Immune Killing towards Triple Negative Breast Cancer
https://doi.org/10.1002/ange.202301202