New Strategy to Develop an mRNA Vaccine for Durable Cancer Immunotherapy and Overcome Cancer Cell Drug Resistance
Data：2021-04-16 | 【 A A A 】 | 【Print】 【Close】
Resistance to chemotherapy or molecularly targeted therapies greatly impedes the efficacy of cancer treatments. The transmembrane P-glycoprotein (P-gp) pumps that efflux drugs are a major mechanism of cancer drug resistance. Inhibiting the function of drug efflux pumps has attracted a lot of attention in past several decades in order to improve the retention/bioavailability of therapeutic agents inside cancer cells. However, those studies have ignored one important fact that the drug efflux pumps play a crucial physiological role in protecting tissues from poisonous xenobiotics and endogenous metabolites that are widely distributed throughout the body. For example, P-glycoprotein (P-gp) is one of the major mechanisms contributing to multidrug resistant capacity of cancer cells, but they are also a major mechanism of the blood-brain barrier (BBB) and intestinal wall to minimize the entry of any toxic substances into the brain and blood, respectively. Therefore, systemic inhibition of the function of P-gp as conducted in the previous studies may cause unexpected side effects.
To address these issues on both the safety and efficacy of P-gp inhibition for cancer chemotherapy, Prof. WANG Hai from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences (CAS), collaborating with Prof. HE Xiaoming from University of Maryland, reported a unique nanoplatform that can precisely deliver P-gp inhibitor in tumor by targeting tumor vasculature and specifically release P-gp inhibitor in tumor under low-power near-infrared (NIR) laser irradiation, to avoid the unexpected accumulation and release of P-gp inhibitor in normal tissues. This nanoplatform (FSCNO) is made of carbon nano-onion and silica surface-decorated with fucoidan. Both in vitro and in vivo studies confirmed that this nanosystem can specifically inhibit the growth of multidrug resistance cancer cells without obvious side effects.