Development of dual-drug-loaded stealth nanocarriers for targeted and synergistic anti-lung cancer efficacy

Abstract

Combination chemotherapy is widely exploited for suppressing drug resistance and achieving synergistic anticancer efficacy in the clinic. In this paper, the nanostructured targeting methotrexate (MTX) plus pemetrexed (PMX) chitosan nanoparticles (CNPs) were developed by modifying methoxy polye (thylene glycol) (mPEG), in which PEGylation CNPs was used as stealth nanocarriers (PCNPs) and MTX was employed as a targeting ligand and chemotherapeutic agent as well. Studies were undertaken on human lung adenocarcinoma epithelial (A549) and Lewis lung carcinoma (LLC) cell lines, revealing the anti-tumor efficacy of nanoparticle drug delivery system. The co-delivery nanoparticles (MTX-PMX-PCNPs) had well-dispersed with sustained release behavior. Cell counting kit-8 (CCK8) has been used to measure A549 cell viability and the research showed that MTX-PMX-PCNPs were much more effective than free drugs when it came to the inhibition of growth and proliferation. Cell cycle assay by flow cytometry manifested that the MTX-PMX-PCNPs exhibited stronger intracellular taken up ability than free drugs at the same concentration. In vivo anticancer effect results indicated that MTX-PMX-PCNPs exhibited a significantly prolong blood circulation, more tumoral location accumulation, and resulted in a robust synergistic anticancer efficacy in lung cancer in mice. The results clearly demonstrated that such unique synergistic anticancer efficacy of co-delivery of MTX and PMX via stealth nanocarriers, providing a prospective strategy for lung cancer treatment.

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of “Stealthy” Nanomaterials

“…Although PEG has been considered for many years as the gold standard of stealth-inducing materials and is still used for the production of stealth drug delivery systems (Pasut et al, 2015;Chen et al, 2018;Cui et al, 2018;Viard et al, 2018;Zhong et al, 2019), many of its limitation have recently been evidenced. First, PEG does not only hinder the interactions of NPs with phagocytic cells responsible for their quick clearance, but also reduce the efficiency of uptake by the target cells NPs are directed against (Zhang et al, 2015).…”

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers

“…Chen et al designed and tested a new formulation MTX-PMX-PCNPs in which two different drugs MTX and pemetrexed (PMX, novel anti-folate with indication for lung cancer and malignant pleural mesothelioma treatment) were bonded with PEGylated chitosan nanoparticles (PCNPs) [223]. Drug release profiles of MTX and PMX were investigated using LLC and A549 cell lines.…”

Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine

“…Controlled anticancer drug release [142] Tumor targeted therapy [143] N-octyl-O-sulfate chitosan Self-assembled polymeric micelles Absorption enhancement of anticancer drug [144,145] Tumor targeted therapy [146][147][148] Increasing stability of drug loaded liposomes [149] 2-[phenylhydrazine (or hydrazine)-thiosemicarbazone]-chitosan Powder Pharmaceutical and food industries [150] (Ser-Ile-Lys-Val-Ala-Val) peptide-modified chitosan Hydrogel Skin substitutes for wound closure in mice [53,151] Galactosylated chitosan (GC) NPs Tumor targeted therapy [152][153][154][155] siRNA delivery [156,157] N-palmitoyl chitosan (NPCS) MPs and micelles Tumor targeted therapy [158,159] O-palmitoyl chitosan (OPC) Liposomes Intestinal drug delivery [160] Hydroxyapatite/CS NPs Drug delivery [161][162][163][164] CS loaded with antioxidant NPs Hydrogel Drug release [165] PEGylated CS NPs Tumor targeted therapy [166][167][168] Chitosan-based vaccine Polyelectrolyte, NPs Intranasal CS-DNA vaccine [169,170] 4. Conclusions CS, as a natural polymer, is actively used in tissue engineering and regenerative medicine as a biomaterial alone, as well as in combination with other polymers.…”