Abstract
The administration of cytotoxic drugs in classical chemotherapy is frequently limited by water solubility, low plasmatic stability, and a myriad of secondary effects associated with their diffusion to healthy tissue. In this sense, novel pharmaceutical forms able to deliver selectively these drugs to the malign cells, and imposing a space-time precise control of their discharge, are needed. In the last two decades, silica nanoparticles have been proposed as safe vehicles for antitumor molecules due to their stability in physiological medium, high surface area and easy functionalization, and good biocompatibility. In this review, we focus on silica-based nanomedicines provided with specific mechanisms for intracellular drug release. According to silica nature (amorphous, mesostructured, and hybrids) nanocarriers responding to a variety of stimuli endogenously (e.g., pH, redox potential, and enzyme activity) or exogenously (e.g., magnetic field, light, temperature, and ultrasound) are proposed. Furthermore, the incorporation of targeting molecules (e.g., monoclonal antibodies) that interact with specific cell membrane receptors allows a selective delivery to cancer cells to be carried out. Eventually, we present some remarks on the most important formulations in the pipeline for clinical approval, and we discuss the most difficult tasks to tackle in the near future, in order to extend the use of these nanomedicines to real patients.
Highlights
In recent years, nanoparticles have emerged as key players in modern medicine, with applications ranging from contrast agents in medical imaging to gene delivery carriers in individual cells
In vitro cytotoxicity studies performed by MTT assay on HeLa human cervical carcinoma cells showed that DOX-magnetic mesoporous silica nanoparticles (MMSNs)@P(NIPAMco-methacrylic acid (MAA)) nanoparticles have an antitumor effect enhanced by the treatment with a magnetic field, confirming a synergistic effect of chemotherapy and magnetic hyperthermia
Many papers have tackled the use of nanoparticle/antibody conjugates for cancer therapy [80,81,82], the first report about targeted therapeutic systems against prostate cancer (PCa) based on silica nanoparticles (SNPs) was recently presented by our group (Figure 9)
Summary
Nanoparticles have emerged as key players in modern medicine, with applications ranging from contrast agents in medical imaging to gene delivery carriers in individual cells. The premature release problem limits the use of a DDS for effective therapy, and plays a major challenge on possible side effects that can be related to the activity of the active principle outside the targeted cells or tissue In this sense, surface functionalization of SNPs with appropriate organic groups allows for the incorporation of the therapeutic molecules by more stable interacting forces, such as ionic bond and covalent bond. One of the main advantages of these “smart systems” is that, by controlling the release of the drug in a specific area of the tissue, they allow, on the one hand, side effects to be minimized and, on the other hand, efficacy of the treatment to be improved [10] At this point, selective cancer therapy needs to develop methodologies to target malignant cells and minimize the impact on healthy tissue. We have introduced a brief description of the most important formulations that are currently in the pipeline for clinical testing
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