Sterically Stabilised Polymeric Mesoporous Silica Nanoparticles Improve Doxorubicin Efficiency: Tailored Cancer Therapy

Abstract

The fruition, commercialisation and clinical application combining nano-engineering, nanomedicine and material science for utilisation in drug delivery is becoming a reality. The successful integration of nanomaterial in nanotherapeutics requires their critical development to ensure physiological and biological compatibility. Mesoporous silica nanoparticles (MSNs) are attractive nanocarriers due to their biodegradable, biocompatible, and relative malleable porous frameworks that can be functionalized for enhanced targeting and delivery in a variety of disease models. The optimal formulation of an MSN with polyethylene glycol (2% and 5%) and chitosan was undertaken, to produce sterically stabilized, hydrophilic MSNs, capable of efficient loading and delivery of the hydrophobic anti-neoplastic drug, doxorubicin (DOX). The pH-sensitive release kinetics of DOX, together with the anticancer, apoptosis and cell-cycle activities of DOX-loaded MSNs in selected cancer cell lines were evaluated. MSNs of 36-60 nm in size, with a pore diameter of 9.8 nm, and a cumulative surface area of 710.36 m 2 /g were produced. The 2% pegylated MSN formulation (PCMSN) had the highest DOX loading capacity (0.98 mg dox /mg msn ), and a sustained release profile over 72 h. Pegylated-drug nanoconjugates were effective at a concentration range between 20-50 µg/mL, inducing apoptosis in cancer cells, and affirming their potential as effective drug delivery vehicles.Molecules 2020, 25, 742 2 of 22 MSNs possess a large active surface area which can be selectively polymerised or functionalised for stimuli-responsive purposes [11], tunable pore size and large pore volumes for the loading and controlled release of the cargo, and have shown favourable tolerance levels both in vitro and in vivo [12][13][14].MSNs are being extensively researched as theranostic devices for diseases, especially for cancer therapy [15]. Conventional cancer treatment options such as surgery, radiotherapy and chemotherapy [16], have not been fully effective, resulting in snowballing recurrence rates and depression in the quality of life [17,18]. Unpleasant side-effects are often linked to the anti-neoplastic drugs used, which act by inhibiting cellular mechanisms of DNA replication that are up-regulated in cancer cells. These cytostatic or cytotoxic compounds usually have low bioavailability and are thus administered at high dosages or for prolonged dosing intervals, leading to systemic side effects at non-specific sites [19,20].Doxorubicin (DOX) remains one of the most efficient anthracycline drugs available and is used in the treatment of diverse cancers, including breast, cervical, bone, gastric and leukaemia [21][22][23]. Despite its popularity, its low solubility [24][25][26], coupled with increased dosing frequencies [27][28][29] has resulted in many associated side effects, including cardiotoxicity [30][31][32], myelosuppression [33,34], induced vomiting with nausea [35,36], and alopecia [18,37]. Critical evaluation of these detrimental side-effects that become more...

Characterization and Evaluation of Bone-Derived Nanoparticles as a Novel pH-Responsive Carrier for Delivery of Doxorubicin into Breast Cancer Cells

“…Moreover, an increase in drug-binding affinity leads to an increase in stability and cellular internalization of the drug-loaded carriers in cancer cells [ 58 ]. For example, in one study, pegylated mesoporous silica NPs showed an enhanced DOX loading efficacy of 0.98 mg (DOX)/mg (MSN) [ 59 ], which facilitated the apoptosis in cancer cells. In another study, a composite of bioengineered silk, EMS2, and magnetic iron oxide (IO) NPs displayed more than two-fold higher DOX-loading capacity compared to plain EMS2 spheres, which catalyzed their potential as a DDS [ 60 ].…”

Current Stimuli-Responsive Mesoporous Silica Nanoparticles for Cancer Therapy

“…Polymeric micelles, including MSNs that have been coated with cross-linking organic and/or inorganic polymers or lipid bilayers that enclose drug that has been electrostatically loaded onto the MSN core. Moodley et al, 2020 described a polyelectrolyte coated MSN that combined organic and inorganic co-polymers grafted on to the superficial surface of the MSN creating a brush-like covering that showed pH-sensitive release of loaded drug [ 85 ].…”

“…A polyelectrolyte coated MSN that showed pH-responsive drug release of 5-fluorouracil (5-FU) and doxorubicin, respectively in a cancer cell models was recently reported. It was concluded that the polymeric brush-coating of TPP, chitosan and PEG when protonated underwent a transformation, opening the MSN pores and releasing the drugs into the targeted cancer cells [ 85 , 110 ]. Yan et al, 2019 developed a MSN system capped with chitosan and folic acid for the pH-responsive release of both a chemotropic drug, DOX and a photosensitizer (pheophorbide a, PA) for targeted and synergistic cancer therapy [ 111 ].…”

Anti-c-myc RNAi-Based Onconanotherapeutics

“…The systems discussed were selectively used for the delivery of anti- c-myc RNAi molecules. Nano-delivery systems such as mesoporous silica nanoparticles [ 100 , 101 ] and magnetic nanoparticles [ 102 , 103 ] are not discussed in this review, but showed potential in drug delivery, which can be considered for as future carriers of siRNA, shRNA, or DsiRNA.…”