Stimuli-responsive mesoporous silica nanoparticles for brain tumor theranostics and drug targeting

Designing a delivery system to target a drug to brain tumors (BT) is a complex process. Drug delivery to BT presents a plethora of obstacles, such as poor bioavailability, drug targeting and its efficacy due to the complexity of the brain's structure, anatomy, and implications of the blood-brain barrier's (BBB) functionality. The anatomical complexity of the brain limits other conventional modes, viz., radiation and major surgery. Moreover, the conventional chemotherapeutics, including radiation therapy for BTs, develop drug resistance and can cause complications further.

This review presents how nanotechnology-based drug delivery systems address these limitations when the drug is administered in a conventional mode. Liposomes, specialized nanoparticles (NPs) (nanoparticulate systems fabricated from polymers and gold), and dendrimers, other nanotechnology-driven carriers, were targeted for BT delivery. Nonetheless, their safety aspects, such as systemic toxicity, off-target effects of therapeutic agents, effective BBB permeability, and drug targeting, are elaborated.

Mesoporous silica nanoparticles (MSNs) offer specialized delivery with the potential of drug targeting directly to BTs via their mesoporous structure, extensive surface area, and adjustable pore size, drug-loading and stimuli-triggered responsiveness. Targeting ligands via surface functionalization enhances the tumor-targeting attributes of MSN modalities while reducing systemic toxicity and off-target effects. To ensure calibrated dosing of anticancer drugs triggered through biophysical response, MSNs can respond to such biophysical or biochemical stimuli originating from the tumor microenvironment (TME). Novel modalities of MSN, previously considered as ineffective owing to BBB restrictions, offer gene-editing tools, small-interfering RNA (siRNA) and further advancement. Clinical oncology, molecular biology, and nanotechnology concordantly develop novel treatment avenues that could significantly modulates desired potential for BT patients.

MSNs are regarded as effective nanocarriers targeting a drug to TME, as elaborated in this review, providing impetus to drug delivery, surface modifiability, and stimuli-triggered mechanisms, including both endogenous and exogenous stimuli.