Facile development, characterization, and evaluation of novel bicalutamide loaded pH-sensitive mesoporous silica nanoparticles for enhanced prostate cancer therapy.

It is a challenge to deliver therapeutics exclusively to cancer cells, while sparing the normal cells. However, pH-sensitive delivery systems have proved to be highly efficient in fulfilling this task due to their ability to provide on-demand and selective release of drug at acidic tumor sites. As a proof of concept, here pH responsive drug delivery system based on mesoporous core shell nanoparticles (NPs) surrounded with poly acrylic acid (PAA) layers were prepared employing a facile synthesis strategy. Bicalutamide (BIC) was encased into surface functionalized MCM-41 nanoparticles via electrostatic interactions. The synthesized NPs were characterized by nitrogen adsorption and desorption isotherms, SEM-EDS, TEM, LXRD, and WXRD. In vitro release studies demonstrated that BIC-MSN-PAA NPs exhibited a higher release in the acidic media which varied inversely with the increase in pH. Further, the results of cell cytotoxicity assay were evident that BICMSNs exhibited more potent killing of both PC-3 and LNCaP cells than free BIC. PAA-MSNs also exhibited an enhanced cellular uptake and prolonged circulation time in vivo. The results are suggestive of the fact that PAA functionalized MSNs can serve as an effective pH-responsive template and hold a great potential ahead in controlled release and effective cancer treatment.

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

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.

The present research was motivated by the dire need to design a targeted and safe Nano-vehicle for delivery of Etoposide (ETE), which would be tolerant of normal cells and exclusively toxic to prostate cancer cells. The folic acid functionalized mesoporous silica nanoparticles (MSNs) constructed by using a facile method acting as a unique selective platform for ETE delivery for effective prostate cancer treatment. FA@MSNs possessed good payload and encouraging in vitro release was obtained for ETE caged inside FA-MSNs compared with ETE-MSNs alone. Further, FA@MSNs exhibited an improved blood compatibility compared with pristine silica. The cellular analysis on PC-3 and LNCaP cell lines unveiled an excellent performance of cytotoxicity. Apoptosis assay confirmed a programmed cell death ruling out necrosis. Most importantly enhanced cellular uptake was obtained for FITC#FA@MSNs. In addition, pharmacokinetic and biodistribution studies in healthy mice indicated a favourable longer circulation time and reduced plasma elimination rate for ETE/FA@MSNs than free ETE. Further, histological and cell cytotoxicity results proved that nanocarriers themselves were safe without any noticeable toxicity. The results showed that FA@MSNs were ideal candidates for safe and effective delivery of ETE and hold a substantial potential as drug delivery vehicles for enhanced prostate cancer therapy.