Missing‐Linker‐Assisted Artesunate Delivery by Metal–Organic Frameworks for Synergistic Cancer Treatment

Abstract

Clinical translation of artesunate (ATS) as a potent antitumor drug has been obstructed by its rapid degradation and low bioavailability. Herein, we report the development of an ATS nanomedicine through the self‐assembly with Mn[Co(CN)6]2/3□1/3 metal–organic frameworks (MOFs) that have hidden missing linkers. The defects in MOFs originating from the missing linkers play a key role in increasing the biological stability and tumor accumulation of ATS. Chlorin e6 (Ce6) and ATS can be co‐loaded into MOFs for a synergistic antitumor efficacy. In the presence of intracellular HCO3−, Mn2+ acts as an efficient catalyst to promote the bicarbonate‐activated H2O2 system which oxidizes ATS to generate reactive oxygen species and induce oxidative death to cancer cells. The released [CoIII(CN)6] linker undergoes a redox reaction with intracellular glutathione to prevent the scavenging ability of reactive oxygen species, contributing to synergistic chemodynamic therapy of ATS and photodynamic therapy of Ce6. Thus, defect‐engineered MOFs with hidden missing linkers hold great promise in advancing the practical use of ATS as an antitumor medicine.

Glycopolymer-Functionalized MOF-808 Nanoparticles as a Cancer-Targeted Dual Drug Delivery System for Carboplatin and Floxuridine

“…For example, against MCF-7 cells, the IC 50 values for (FUDR+CARB)@MOF-808 and (FUDR+CARB)@MOF-808_act normalized to CARB loading are 4.2 and 4.4 μg mL –1 , respectively, slightly lower than CARB@MOF-808_act (5.4 μg mL –1 CARB) but significantly lower compared to free CARB (59.4 μg mL –1 ). Nevertheless, the decreases in CARB-normalized IC 50 values for the dual drug-loaded samples compared to the single drug-loaded samples confirm the beneficial effect of concomitantly delivering FUDR with CARB and show that this system is a rare example of combination drug delivery from MOF nanoparticles. − …”

A multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced chemodynamic therapy

“…Delivering exogenous peroxide compounds that generate ROS with the assistance of transition metal ions would avoid the restriction of insufficient endogenous peroxide compounds and boost the ROS generation. AS, a natural product with an endoperoxide bridge, is found to produce ROS in the presence of manganese ions ( Wang D. et al, 2021 ). Hence, we further examined the ROS generation ability of AS in the presence of manganese-based materials.…”

“…In this regard, there are two main strategies to replenish intratumoral peroxide species including amplification of H 2 O 2 production and delivery of other peroxide compounds. Some of the natural endoperoxide compounds such as artesunate (AS) can serve as exogenous peroxide species for replenishing the shortage of intracellular peroxide pools and boosting the Mn 2+ -mediated CDT ( Lin et al, 2020 ; Wang D. et al, 2021 ; Jin et al, 2021 ). Therefore, delivery of AS demonstrates the prominent advantages in overcoming insufficient H 2 O 2 for effective CDT.…”

Synergistically Enhancing Tumor Chemotherapy Using an Aggregation-Induced Emission Photosensitizer on Covalently Conjugated Molecularly Imprinted Polymer Nanoparticles

“…To improve the in vivo pharmacokinetics (PK) of drugs and reduce the off-target side effects of conventional antitumor drugs, people take many efforts on developing drug delivery systems, and some of them have been used in clinics, such as Abraxane, Onivyde, and DOXIL. − However, because the process of tumorigenesis is polygenic and heterogeneous, data from clinical trials are not as promising, and most them still fail to reach desired therapeutic effect. Alternately, synergistic enhancement of chemodrug by integrating other therapy methods can be an effective strategy for attacking tumor cells from different angles. − Photodynamic therapy (PDT) owns significant advantages, such as negligible drug resistance, low systemic toxicity, and minimal side effects. − Recent studies indicate that the sensitivity of cancer cells to chemotherapeutics can be increased to a great extent by combining with PDT, which leads to a reduction in drug dose, alleviates resistance to the drugs, and improves therapeutic efficiency. − But how to assemble different units in a nanoplatform to make full use and minimize side effects of chemodrugs, photosensitizers (PSs), and scaffolds is still a challenging and pressing task.…”