In vitro and in vivo evaluation of folate receptor-targeted a novel magnetic drug delivery system for ovarian cancer therapy

Pathak

Artificial Cells, Nanomedicine, and Biotechnology

et al. 2019

Ovarian cancer is the second most common gynaecological malignancy. It usually occurs in women older than 50 years, and because 75% of cases are diagnosed at stage III or IV it is associated with poor diagnosis. Despite the chemosensitivity of intraperitoneal chemotherapy, the majority of patients is relapsed and eventually dies. In addition to the challenge of early detection, its treatment presents several challenges like the route of administration, resistance to therapy with recurrence and specific targeting of cancer to reduce cytotoxicity and side effects. In ovarian cancer therapy, nanocarriers help overcome problems of poor aqueous solubility of chemotherapeutic drugs and enhance their delivery to the tumour sites either by passive or active targeting, and thus reducing adverse side effects to the healthy tissues. Moreover, the bioavailability to the tumour site is increased by the enhanced permeability and retention (EPR) mechanism. The present review aims to describe the current conventional treatment with special reference to passively and actively targeted drug delivery systems (DDSs) towards specific receptors designed against ovarian cancer to overcome the drawbacks of conventional delivery. Conclusively, targeted nanocarriers would optimise the intra-tumour distribution, followed by drug delivery into the intracellular compartment. These features may contribute to greater therapeutic effect. ARTICLE HISTORY

Section: Skov-3 Female Balb/c Mice 88mentioning

confidence: 98%

RETRACTED ARTICLE: Nanoscale drug delivery strategies for therapy of ovarian cancer: conventional vs targeted

Pathak

Artificial Cells, Nanomedicine, and Biotechnology

et al. 2019

“…For instance, the chitosan-coated mixed micellar nanocarriers loaded with DOX and siRNA were used to provide pH responsiveness, and the nanocomplexes showed better DOX release in acidic tumor pH environments. 20 In addition, many tumor cells have specific expression of numerous receptors which are very important for malignant tumor proliferation, such as folate receptor 21 and biotin receptor. 22 Particularly in HCC, the galactose and N-acetylgalactosamine-terminated glycoproteins are recognized by asialoglycoprotein receptor (ASGPR) located on the surface of liver cancer cells, 23 hence ASGPR-mediated targeted delivery system has been regarded as one of the most efficient methods for treating HCC.…”

Section: Introductionmentioning

confidence: 99%

pH-sensitive doxorubicin-loaded polymeric nanocomplex based on β-cyclodextrin for liver cancer-targeted therapy

Yang¹,

Du²,

Cui³

et al. 2019

IJN

Background: Doxorubicin (DOX) is one of the most effective treatments for hepatocellular carcinoma (HCC), but is restricted by its poor pharmacokinetics. Herein, we exploited efficient targeted drug delivery systems and they have been found to be a worthy strategy for liver cancer therapy. Materials and methods: We investigated polymeric nanoparticles which were synthesized based on host-guest interaction between β-cyclodextrin and benzimidazole. The properties of nanoparticles with regard to size/shape, encapsulation efficiency, and drug release were investigated using conventional experiments. Cell proliferation assay in vitro, cell uptake assay, and cell apoptosis analysis were used to investigate cytotoxicity, uptake, and mechanism of targeted supramolecular prodrug complexes (TSPCs)-based self-assemblies and supramolecular prodrug complexes (SPCs)-based self-assemblies. Results: The pH-sensitive lactobionic acid (LA)-modified pH-sensitive self-assemblies were synthesized successfully. The results of in vitro released assay showed that the accelerated released of DOX from TSPCs-based self-assemblies with the decrease of pH value. When TSPCs-based self-assemblies were taken up by HepG2 cells, they demonstrated a faster release rate under acidic conditions and proved to have higher cytotoxicity than in the presence of LA. A mechanistic study revealed that TSPCs-based self-assemblies inhibited liver cell proliferation by inducing cell apoptosis. Conclusion: The pH-sensitive nanocomplex, as liver-targeted nanoparticles, facilitated the efficacy of DOX in HepG2 cells, offering an appealing strategy for the treatment of HCC.

Artificial Cells, Nanomedicine, and Biotechnology

“…A few dextran-coated MNP formulations have been approved as MRI contrast agents by the FDA and EMA [7]. A raise to a more desirable or better quality of recourse of tumour specific hitting, water-soluble folate conjugates are designed and synthesized as the folate conjugation facilitates the uptake by folate-receptor overexpressed cells [17].…”

Section: Introductionmentioning

confidence: 99%

“…Covalent linking of anticancer drugs has been a strategy to aim at cancer cells [17][18][19]. However, such strong bonds between the polymer and the drug need to be cleaved so that the prodrug action becomes tangible.…”

Section: Introductionmentioning

confidence: 99%

Folate-molecular encapsulator-tethered biocompatible polymer grafted with magnetic nanoparticles for augmented drug delivery

Ramasamy

David

Enoch

2018

Magnetic ferrite nanoparticles (MNPs) coated with biocompatible polymers capable of drug loading and release are fascinating nanostructures for delivering anti-cancer drugs. Herein, we report the synthesis and characterization of a novel β-cyclodextrin-folate-tethered dextran polymer. Nickel-zinc ferrite nanoparticles are prepared and coated with the polymer to form a biocompatible hybrid magnetic nanocarrier. To establish the significance of folate unit of the polymer in anticancer activity, a similar derivatized polymer, i.e. β-cyclodextrin-dextran conjugate without folate tether is used for comparison. The size of the hybrid MNPs is ∼20 nm, which is a size suitable for cancer drug targeting. The polymer-coated magnetic nanocarriers are soft ferromagnets as suggested by their narrow magnetic hysteresis loops. The anticancer drug camptothecin (CPT) is loaded on the magnetic nanocarriers. The drug loading efficiency is observed to be above 92%. The nanocarriers show sustained in vitro drug release for above 45 h. The in vitro cytotoxicity studies reveal that the loaded CPT retains its potency in the nanocarrier and the folate-tethered nanocarrier shows better anticancer activity than the one which does not carry a folate unit. The magnetic nanocarrier is suitable for magnetic field-guided drug transport, enhanced drug loading and release and folate receptor-mediated endocytotic uptake of drugs by cancer cells.