Folic Acid–Functionalized Metal-Organic Framework Nanoparticles as Drug Carriers Improved Bufalin Antitumor Activity Against Breast Cancer

Abstract

Bufalin (Buf), an active ingredient of the traditional Chinese medicine Chansu, is known to have anticancer effects for breast cancer. However, its poor solubility, high toxicity, and extensive side effects limit its use. Metal-organic frameworks (MOFs) are a class of promising drug delivery systems known for their high porosity. Here, we designed and constructed pH-sensitive and redox-responsive folic acid–modified MOFs as drug carriers of Buf (FA-MOF/Buf). Moreover, the anticancer activity of nanomedicines was also explored in vitro and in vivo. Compared to free Buf, the FA-MOF/Buf nanoparticles demonstrated improved water solubility and stability, higher intracellular uptake, and enhanced cytotoxicity in breast cancer cells in vitro. Furthermore, it displayed improved accumulation in the tumor site, enhanced anticancer activity, and reduced side effects in vivo. Our results demonstrated that FA-MOF could be developed as a potential delivery system for Buf to improve its antitumor activity for breast cancer treatment.

Synthesis and Application of MOF-808 Decorated with Folic Acid-Conjugated Chitosan as a Strong Nanocarrier for the Targeted Drug Delivery of Quercetin

“…The results are in agreement with those reported previously, which indicates that the presence of FRs on cancerous cells facilitates cellular uptake of folate-conjugated MOFs for anticancer drug delivery. In addition, it supports the idea that these kinds of nanocarriers effectively promote cell death through the apoptosis route. , …”

“…In addition, it supports the idea that these kinds of nanocarriers effectively promote cell death through the apoptosis route. 120,122…”

Bufalin-loaded vitamin E succinate-grafted chitosan oligosaccharide/RGD-conjugated TPGS mixed micelles inhibit intraperitoneal metastasis of ovarian cancer

“…Moreover, due to its toxicity, insolubility, rapid metabolism and short half-life, the applications of BU for cancer treatment are limited. (Gao et al 2021a, b;Yang et al 2021a, b) Accordingly, multiple nanodelivery systems have been investigated for loading BU to achieve precise targeting, enhance its antitumor effects, reduce its toxicity, and prolong its half-life (Hu et al 2020;Zeng et al 2021).…”

“…Several studies have taken advantage of nano-drug delivery systems to target delivery of bufalin for enhance its antitumor therapy and attenuate toxicity, such as platelet membrane biomimetic nanoparticle, liposomes, polymeric prodrug, bovine serum albumin nanoparticle, monodisperse mesoporous silica nanoparticle, metal-organic frameworks(MOFs) and so on (Tian et al 2014;Ning et al 2022;Zeng et al 2021;Hu et al 2012;Wen et al 2017;Ettlinger et al 2022). Zeng et al designed pH-sensitive and redox-responsive folic acid-modified MOFs as drug carriers of bufalin (FA-MOF/Buf ), which could improve water solubility and stability, higher intracellular uptake, and enhanced antitumor effect of bufalin in breast cancer (Zeng et al 2021). Ning et al prepared a monodisperse mesoporous silica nanoparticle to load lenvatinib and bufalin for targeted delivery to cholangiocarcinoma, which indicated a superior therapeutic effect than free drugs (Ning et al 2022).…”

Current trends in the synthesis, characterization and application of metal-organic frameworks

“…A report on the in vitro and in vivo experiments of the MOF showed a high drug loading and encapsulation efficiency, high stability, and long circulation time, and it permitted longer sustained drug release in inflamed joint tissues. 14 Zeng et al 249 designed and constructed pH-sensitive and redox-responsive folic acid-modified MOFs (FA-MOF/Buf) as drug carriers of bufalin with anticancer effects for breast cancer. The anticancer activity of nanomedicines was explored in vitro and in vivo and the FA-MOF/Buf nanoparticles demonstrated improved water solubility and stability, higher intracellular uptake, and enhanced cytotoxicity in breast cancer cells in vitro .…”