Tailor-made pH-sensitive polyacrylic acid functionalized mesoporous silica nanoparticles for efficient and controlled delivery of anti-cancer drug Etoposide

Abstract

A multifaceted therapeutic platform has been proposed for controlled delivery of Etoposide (ETS) leading to a synergistic advantage of maximum therapeutic efficacy and diminished toxicity. A state of the art pH responsive nanoparticles (NPs) MSNs-PAA consisting of mesoporous silica nanoparticles core and polymeric shell layers, were developed for controlled release of model anti-cancer drug ETS. Graft onto strategy was employed and amination served as an interim step, laying a vital foundation for functionalization of the MSN core with hydrophilic and pH responsive polyacrylic acid (PAA). MCM-41-PAA were investigated as carriers for loading and regulated release of ETS at different pH for the first time. The PAA-MSNs contained 20.19% grafted PAA as exhibited by thermogravimetric analysis (TGA), which enormously improved the solubility of ETS in aqueous media. The synthesized PAA-MSNs were characterized by various techniques viz, SEM-EDS, TEM, BET, FT-IR and powder XRD. ETS was effectively loaded into the channels of PAA-MSN via electrostatic interactions. The cumulative release was much rapid at extracellular tumor (6.8) and endosomal pH (5.5) than that of blood pH (7.4). Hemolysis study was done for the prepared NPs. MTT assay results showed that the drug-loaded ETS-MCM-41-PAA NPs were more cytotoxic to both prostate cancer cells namely PC-3 and LNCaP than free ETS, which was attributed to their slow and sustained release behavior. The above results confirmed that PAA-MSN hold a great potential as pH responsive carriers with promising future in the field of cancer therapy.

Etoposide encased folic acid adorned mesoporous silica nanoparticles as potent nanovehicles for enhanced prostate cancer therapy: synthesis, characterization, cellular uptake and biodistribution

“…WAXRD patterns were recorded to determine the crystalline nature of ETE (Figure 3(II)). Sharp peaks were observed at theta values of 10.9, 16.5, 19.9, 21.3, 24.1 and 25.9 [16]. For ETE loaded MSNs absence of crystalline phase was observed.…”

“…MCM-41 mesoporous silica nanoparticles were synthesized based on template synthesis method with few alterations [15,16]. For the fabrication of MSNs, 2.21 grams (g) of CTAB playing a role of the structural template was dissolved in deionized water and blended for 5 min (min).…”

“…The asynthesized MSNs obtained in the form of dry powder were subjected to calcination at 823 K for 6 h to completely evacuate the template. Further, the calcinated MSNs were added to toluene in an RBF followed by addition of APTS at 70 C for 12 h. After the reaction was complete, it was allowed to cool at RT and then filtered, followed by thorough washing with methanol and complete drying [16,17]. The product was marked as A@MSN.…”

Etoposide Loaded SPION‐PNIPAM Nanoparticles Improve the in vitro Therapeutic Outcome on Metastatic Prostate Cancer Cells via Enhanced Apoptosis

“…[26] Recently, Saroj and Rajput have shown that Etoposide encapsulated poly(acrylic acid)-mesoporous silica nanoparticles have more therapeutic potential than the free drug on prostate cancer cells. [27] Inorganic nanoparticles which offer an imaging modality are also very popular since they allow the combination of imaging with therapy. Superparamagnetic iron oxide nanoparticles (SPION) are the most popular of such nanoparticles, since they are already used in the clinic as MRI contrast agents.…”

Structure and Dynamics of Pyrene-Labeled Poly(acrylic acid): Molecular Dynamics Simulation Study

“…Water-soluble pH-responsive polymers, labeled covalently with fluorescent dyes, have attracted a major focus of interest in polymer photophysics due to their stimuli-responsive self-organizing behavior [1][2][3]. They have revealed numerous important applications for surface modification, structuring and, in particular, rheology control [1].…”