Metal (Au)-Decorated Chitosan-l-Arginine Polymeric Vector for Codelivery of Gefitinib and miR125b for Lung Cancer Therapy

Abstract

The progression of lung cancer is highly associated with the aberrant activation of epidermal growth factor receptor (EGFR) tyrosine kinase and the positive feedback loop between cancer cells and tumor-associated macrophages (TAMs). Hence, we use chitosan (CS) as a backbone and L-Arginine (L-Arg) as lateral chains to synthesize a biocompatible copolymer [(CS)-co-(L-Arg)]. With the electrostatic coupling between Au particles and [(CS)-co-(L-Arg)], the copolymer was further fabricated into [(CS)-co-(L-Arg)]-(AuNPs) nanoparticles with a nest-type perforated structure (CAAu NPs). Owing to the perforated structure and cationic property, CAAu NPs exhibit a high capacity for coloading of gefitinib (GFT) and miR125b, forming GFT-miR125b@CAAu nanomedicine. GFT-miR125b@CAAu shows a pulmonary-anchoring advantage, which is attributed to the mucoadhesion of the CS backbone. Meanwhile, L-Arg residues play a biomimetic role, which endows GFT-miR125b@CAAu with efficient internalization by cancer cells through Arg transportermediated endocytosis. Within the acidic tumor microenvironment, the electrostatic bonding of GFT-miR125b@CAAu cleaves, which facilitates pH-responsive release of GFT and miR125b. By combination of EGFR blocking and miR125b augmenting, GFT-miR125b@CAAu nanomedicine not only inhibits cancer cell survival but also deactivates protumoral TAMs, implementing a combination therapy against lung cancer.

Synthesis of Fe3O4 core/MIL-100(Fe) shell nanocomposites for tumor chemo-ferroptosis combination therapy and MR imaging

“…Moreover, the hydrodynamic diameter (∼420 nm, figure S3(a)) and zeta potential (−16.15 mV, figure S3(b)) of the FM were also determined by using dynamic light scattering (DLS). It was observed that the mean diameter in water suspension was significantly higher than one found during TEM analyze [33]. In addition, the crystal structures of the as-synthesized nanomaterials were further examined by XRD patterns (figure 1(d)).…”

Thermoresponsive [(PLA)-b-(Car)] based frustum-shaped capsules with extended porosity for biosensing and biomedical applications

“…As mentioned in Fig. 5a, five different concentrations (5,10,25,50, and 100 µg mL -1 ) of [(PLA)-b-(Car)] sample incubated with cell lines for treatment and obtained results reports greater than 85% cell viability with all the concentrations (details in section 2.6 Cell viability assay) [16,46,47].…”

“…Therefore, developing thermoresponsive and multifunctional nanosystems is novel and propagatory towards nanobioapplications as well real real-time industrial usage. Until now, quantum dots (QDTs) [11][12][13][14][15], carbon nanotubes (CNTs) [16][17][18], nanowires, nanorods, coreshell nanoparticles, micelles, etc., have been reported to their kind but thermoresponsive and morphologically modifiable [(PLA)-b-(Car)] based 1) frustum shaped nanoparticles, 2) elliptical cone shaped nanoparticles and 3) dome-shaped nanoparticles with huge porosity is newer and interesting concept to evaluate the catalytic activity for biomedical regulations [19][20][21]. Consequently, Scheme 1 deliberates steps involved in the synthesis of [(PLA)-b-(Car)] followed by the design and development of different types of nanoparticles and their stimuliresponsive catalytic activity through the fluorescence measurement of [(Cys)-(Au + )] [22][23][24][25][26].…”

Recent Advances in Boosting EGFR Tyrosine Kinase Inhibitors-Based Cancer Therapy

“…Targeting modulation TAM from M2 to M1 is widely applied to potentiate cancer immunotherapy, and this strategy is also applicable here to strengthen TKI therapy. A nest-type nanosystem loading Gefi and miR125b, a micro-RNA to deactivate M2 phenotype of TAMs, was developed to simultaneously block EGFR pathway in cancer cells and suppress M2 polarization of TAMs, demonstrating better inhibition of Lewis lung carcinoma than monotherapy . Another recent study revealed that this strategy is amenable to tackling the acquired resistance of EGFR T790M in NSCLC, where vorinostat was used as a TAM reprogramming agent to repolarize the protumor M2 phenotype to M1 and elevate ROS level in cancer cells, restoring the sensitivity of EGFR T790M -positive cancer cells to Gefi.…”