Abstract:With the widespread clinical use of drug combinations, the incidence of drug–drug interactions (DDI) has significantly increased, accompanied by a variety of adverse reactions. Drug transporters play an important role in the development of DDI by affecting the elimination process of drugs in vivo, especially in the pathological state. Tubulointerstitial fibrosis (TIF) is an inevitable pathway in the progression of chronic kidney disease (CKD) to end-stage renal disease. Here, the dynamic expression changes of … Show more
“…Western blot analysis was performed to evaluate the expression of drug resistance-related proteins caused by the different treatments. We found that free CDDP exhibited no significant effect on MDR1 expression, resulting in multidrug resistance. − Free Nira, MCT, and MNT moderately reduced MDR1 expression, and the effect of MNCT was the most significant owing to the synergistic effect of Nira. In the SKOV3 DDP cells, the drug-loaded NPs exhibited a higher decrease in MDR1 expression than the single free drugs.…”
Cisplatin (CDDP) is a widely used chemotherapeutic drug
with proven
efficacy for treating tumors. However, its use has been associated
with severe side effects and eventually leads to drug resistance,
thus limiting its clinical application in patients with ovarian cancer
(OC). Herein, we aimed to investigate the success rate of reversing
cisplatin resistance using a synthetic, multitargeted nanodrug delivery
system comprising a Mn-based metal–organic framework (Mn-MOF)
containing niraparib (Nira) and CDDP alongside transferrin (Tf) conjugated
to the surface (Tf-Mn-MOF@Nira@CDDP; MNCT). Our results revealed that
MNCT can target the tumor site, consume glutathione (GSH), which is
highly expressed in drug-resistant cells, and then decompose to release
the encapsulated Nira and CDDP. Nira and CDDP play a synergistic role
in increasing DNA damage and apoptosis, exhibiting excellent antiproliferation,
migration, and invasion activities. In addition, MNCT significantly
inhibited tumor growth in tumor-bearing mice and exhibited excellent
biocompatibility without side effects. Furthermore, it depleted GSH,
downregulated multidrug-resistant transporter protein (MDR) expression, and upregulated tumor suppressor protein phosphatase
and tensin homolog (PTEN) expression, consequently
reducing DNA damage repair and reversing cisplatin resistance. These
results indicate that multitargeted nanodrug delivery systems can
provide a promising clinical approach to overcoming cisplatin resistance.
This study provides an experimental basis for further investigation
into multitargeted nanodrug delivery systems to reverse cisplatin
resistance in patients with OC.
“…Western blot analysis was performed to evaluate the expression of drug resistance-related proteins caused by the different treatments. We found that free CDDP exhibited no significant effect on MDR1 expression, resulting in multidrug resistance. − Free Nira, MCT, and MNT moderately reduced MDR1 expression, and the effect of MNCT was the most significant owing to the synergistic effect of Nira. In the SKOV3 DDP cells, the drug-loaded NPs exhibited a higher decrease in MDR1 expression than the single free drugs.…”
Cisplatin (CDDP) is a widely used chemotherapeutic drug
with proven
efficacy for treating tumors. However, its use has been associated
with severe side effects and eventually leads to drug resistance,
thus limiting its clinical application in patients with ovarian cancer
(OC). Herein, we aimed to investigate the success rate of reversing
cisplatin resistance using a synthetic, multitargeted nanodrug delivery
system comprising a Mn-based metal–organic framework (Mn-MOF)
containing niraparib (Nira) and CDDP alongside transferrin (Tf) conjugated
to the surface (Tf-Mn-MOF@Nira@CDDP; MNCT). Our results revealed that
MNCT can target the tumor site, consume glutathione (GSH), which is
highly expressed in drug-resistant cells, and then decompose to release
the encapsulated Nira and CDDP. Nira and CDDP play a synergistic role
in increasing DNA damage and apoptosis, exhibiting excellent antiproliferation,
migration, and invasion activities. In addition, MNCT significantly
inhibited tumor growth in tumor-bearing mice and exhibited excellent
biocompatibility without side effects. Furthermore, it depleted GSH,
downregulated multidrug-resistant transporter protein (MDR) expression, and upregulated tumor suppressor protein phosphatase
and tensin homolog (PTEN) expression, consequently
reducing DNA damage repair and reversing cisplatin resistance. These
results indicate that multitargeted nanodrug delivery systems can
provide a promising clinical approach to overcoming cisplatin resistance.
This study provides an experimental basis for further investigation
into multitargeted nanodrug delivery systems to reverse cisplatin
resistance in patients with OC.
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