Self-assembled dihydroartemisinin nanoparticles as a platform for cervical cancer chemotherapy

Abstract

Dihydroartemisinin (DHA) is a potent anti-cancer drug that has limited clinical applications due to poor water solubility and low bioavailability. We designed a biodegradable poly(ethylene glycol) methyl ether-poly(ε-caprolactone) (MPEG-PCL) micelle carrier for DHA using the self-assembly method. The DHA/MPEG-PCL nanoparticles were spherical with an average particle size of 30.28 ± 0.27 nm, and released the drug in a sustained manner in aqueous solution. The drug-loaded nanoparticles showed dose-dependent toxicity in HeLa cells by inducing cycle arrest and apoptosis. Furthermore, compared to free DHA, the DHA/MPEG-PCL nanoparticles showed higher therapeutic efficacy and lower toxicity in vivo , and significantly inhibited tumor growth and prolonged the survival of tumor-bearing nude mice. In addition, the tumor tissues of the DHA/MPEG-PCL-treated mice showed a marked decline in the in situ expression of proliferation and angiogenesis markers. Taken together, the self-assembled DHA/MPEG-PCL nanoparticles are a highly promising delivery system for targeted cancer treatment.

Dihydroartemisinin synergistically enhances the cytotoxic effects of oxaliplatin in colon cancer by targeting the PHB2‐RCHY1 mediated signaling pathway

“…5,6 Increasing evidence has shown that DHA can inhibit the growth of various cancers, including breast cancer, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, CC, and cervical cancer. [7][8][9][10][11] The role of DHA in regulating tumorigenesis is being increasingly appreciated as its preferential antiproliferative effects on cancer versus normal cells have been revealed. 12 In this study, we found that DHA not only inhibited CC cell proliferation but also synergistically enhanced the cytotoxicity of oxaliplatin in CC cells.…”

“…Dihydroartemisinin (DHA), a derivative of ART, is the active metabolite of ART compounds and has been reported to exhibit strong antiviral, antibacterial, and anticancer activities 5,6 . Increasing evidence has shown that DHA can inhibit the growth of various cancers, including breast cancer, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, CC, and cervical cancer 7–11 . The role of DHA in regulating tumorigenesis is being increasingly appreciated as its preferential antiproliferative effects on cancer versus normal cells have been revealed 12 …”

Development of nanoscale drug delivery systems of dihydroartemisinin for cancer therapy: A review

“…In many cases, more than one type of polymer can be contained in a DHA-encapsulated system. For instance, DHA-phospholipid complex NPs coated with biodegradable poly(lactic-co-glycolic acid) (PLGA) [103] or PEG methyl ether-poly(e-caprolactone) (MPEG-PCL) DHA polymeric micelles [104] were prepared to prevent drugs from rapid blood/renal clearance and suppress premature burst release. When compared with the unformulated drug, the polymeric NPs significantly enhanced the cytotoxicity of DHA.…”

“… DHA formulation Cancer Type Animal model Dosage Route Safety issues Ref. Tf-8arm-PEG-DHA NPs Lewis lung carcinoma LLC tumor-bearing female C57BL/6 mice 5 mg/kg or 10 mg/kg DHA every 2 d IV injection Reduced hypersensitivity reactions; no severe hematotoxicity [101] DHA-PEG-PTX nanosystems Colorectal cancer HT-29 tumor-bearing Balb/c nude mice 5 mg/kg PTX and 10 mg/kg DHA every 3 d IV injection No significant body weight loss [102] DHA/MPEG-PCL NPs Cervical cancer HeLa tumor-bearing female athymic BALB/C nude mice 20 mg/kg DHA every 2 d IV injection No significant pathological changes, weight loss or inflammatory lesions [104] DOX and DHA coencapsulated Soluplus®-TPGS mixed micelles Breast cancer MCF-7 xenografted female BALB/c nude mice 15 mg/kg DHA and/or 15 mg/kg DOX every 2 d IV injection Reduced the cardiotoxicity; avoided hepatic damage and necrosis [105] OxPt/DHA core-shell particles Colorectal cancer CT26 or MC38 tumor-bearing BALB/c, C57Bl/6 wild-type or Rag 2−/− mice 8 mg/kg OxPt, 2.86 mg/kg DHA, and/or 75 µg PD-L1 antibody every 3 d IP injection Reduced peripheral neuropathy [106] R 8 modified epirubicin–DHA liposomes Non-small-cell lung cancer A549 tumor-bearing BALB/c nude mice 3 mg/kg epirubicin; (epirubicin/DHA= 1:5, molar ratio) every 2 d IV injection Neglected systemic toxicity [116] LDLR-targeted lipid NPs coloading sorafenib and DHA Hepatocellular carcinoma HepG2 tumor-bearing BALB/c nu/nu nude mice 5 mg/kg SRF and/or DHA every 3 d IV injection Reduced body weight loss as compared to free drugs [118] Alkyl glycoside-modified DHA liposomes Hepatocellular carcinoma H22 tumo...…”

Co-Targeting Tumor Angiogenesis and Immunosuppressive Tumor Microenvironment: A Perspective in Ethnopharmacology

“…Sibusiso et al have reported the nanosystem doped with artemisinins, including polymeric, metal-based, and lipid nanoparticles, against cancer by enhancing effects recuperating poor solubility and bioavailability and targeting delivery ( Alven and Aderibigbe, 2020 ). Concurrently, Yun et al depicted a biodegradable poly (ethylene glycol) methyl ether-poly (ε-caprolactone) (MPEG-PCL) loading dihydroartemisinin (DHA) had allowed for a stronger anti-angiogenic effect than free DHA ( Lu et al, 2020 ).…”