Engineered design of mesoporous silica-based nanoparticles functionalised by layer-by-layer technique as multifunctional nanotheranostic agents for cancer treatment

Cancer is the second leading cause of death globally and it is responsible for an estimated 9.6 million deaths in 2018, with 13.2 million deaths are expected in 2030 for global population. Due to the limits of conventional cancer treatments currently in use, an emerging field of treatments, known as nanotheranostics, has been studied for the past years, demonstrating a great potential thanks to the use of nano sized platforms with the dual capability of therapeutics and diagnostics. Researchers have focused on developing innovative systems in order to improve drug delivery at the specific target sites, kinetic drug release, biodistribution, and multimodal therapy trough the combination of different therapeutic methods such as chemotherapy and phototherapy. In this work, starting from state-of-the-art about nanotheranostic efficient systems, we have investigated the design of an innovative theranostic nanoparticle built through a bottom-up strategy, and characterised by a mesoporous silica-based nanoparticle (MSN) as internal core. According to the literature, MSNs have been widely applied in theranostic field as drug delivery carriers thanks to their high surface area, controllable pore size and morphology, and chemically modifiable surface. Particularly, synthesized MSN with an expected diameter of 50 nm, loaded with tripazamine (TPZ), can be then functionalized with 3-aminopropyltriethoxysilane (APTES) to obtain a positively charged MSN-NH_2. Layer-by-layer self-assembly strategy has been proposed to coat MSN-NH_2 with specific biomaterials in order to provide a multifunctional shell structure, incorporating another drug as Doxorubicin for a dual drug effect. Two charged bilayers of hyaluronic acid and poly(L-lysine) can be alternating deposited on the MSN-NH_2 to obtain a pH-responsive structure able to control the kinetics release. For providing a combination of different therapies, the cationic compound in the first bilayer is made up of porphyrin-based photosensitizers (PSs), key factors for photodynamic therapy (PDT). Additionally, according to the literature, PSs have demonstrated efficiency in NIR fluorescence, contributing to imaging-guided tumour targeted therapy. Moreover, PSs, generating deleterious reactive oxygen species (ROS) to irreversible damage tumour cells, TPZ, a drug that is only cytotoxic to hypoxic cells, strongly cooperate with PDT. Finally, the external layer can be functionalised with the hydrophilic chain polymer polyethylene glycol (PEG) linked with folic acid (FA) to avoid the effect of immune system, improve biostability and increase circulation time in the blood environment, and to promote active targeting to the tumour mass. The active targeting of the PEG-linked molecule is modifiable grafting specific biomolecules like antibodies depending on the treated tumour. The whole platform has been designed to satisfy the biocompatibility standard requirements set by Food and Drug Administration (FDA). In conclusion, a brief discussion on a MatLab computational study is proposed as a possible future way to analyse and predict kinetics release from a multilayer platforms in a biological medium in order to efficiently select materials and biomolecules doses to insert in the systems, reducing time consumption and costs for experimental tests.