## 1 Introduction  
Worldwide, cancer is the second leading cause of death at ages under 70. As estimated, 10 million cancer deaths and 19.3 million new cancer cases occurred in 2020 [1]. Cancer cells can easily proliferate indefinitely and quickly relocate to normal and intact tissues. The cancerous tissues have an excessive metabolite accumulation of the biological microenvironment, leading to increased acidity and hypoxia [2; 3]. Treating cancer cells could be achieved using stimuli-sensitive drug delivery systems (DDSs), which are designed to selectively release drug molecules inside the targeted microenvironment of diseased tissues to improve anti-cancer activity [4; 5]. The penetration of the drug-loaded nanocarriers into the desired sites of tumour cells rely upon different factors such as cellular internalization, tumour tissue penetration, and prolonged blood circulation [6; 7]. Designing an ideal drug delivery system requires the release of the therapeutic agent to the desired site in the right dose within a specified period of time [8]. Mesoporous silica nanoparticles (MSNs) have been suggested to be a good platform for in vivo delivery of anti-cancer drugs to tumour tissues [9; 10; 11]. Silica has been considered as a safe material by the Food and Drug Administration (FDA) [12]. MSNs have several characteristics such as stable mesostructure, high surface area and pore volume, uniform pore size, modifiable morphology, and outstanding biocompatibility [13; 14; 15]. In the biological environments, unmodified MSNs loaded with anti-cancer drugs are more likely to agglomerate and suffer from lack of specificity [16; 17]. These drawbacks have been significantly minimized by the incorporation of biocompatible and stimuli-responsive polymers into the MSNs surface to produce materials with different morphologies such as Yolk-shell and brushes [18; 19]. Such polymers allow the host-encapsulated drug molecules to be released in the targeted site in an optimal manner [20; 21; 22]. Many biocompatible polymeric shells are considered to be stable in biological environments, which could minimize the side effects and toxicity of DDSs [23; 24]. Recently, many studies have been reported on the development of MSN-based pH-responsive systems as a mean of controlling the drug release [25; 26]. Polymers that are pH-responsive can undergo reversible and controllable confirmational structure changes by changing the pH value of their environments [27]. For illustration, poly(N,N diethylaminoethyl methacrylate), poly(N,N -dimethylaminoethyl methacrylate), and poly(b-amino ester) are base polymers and their amine end-groups experience structural changes when they become protonated. [PERSON] et al. synthesised poly(2-(tert-butylaminoethyl methacrylate) brushes (PTBAEMA) grafted into MSNs using surface-initiated atom transfer radical polymerization (SI-ATRP) techniques. It was found that PTBAEMA brushes became swollen and protonated at a low pH value. In contrast, PTBAEMA brushes became collapsed and deprotonated at a high pH value (\(>\)7.5) [28]. Another example of a base polymer is poly(2-(diethylaminoethyl methacrylate) (PDEAEMA), which can change from hydrophobic to hydrophilic in an acidic medium due to protonation process of tertiary amino groups [29]. [PERSON] et al. reported the synthesis of hollow mesoporous silica nanoparticles, coated with PDEAEMA brushes terminated with glucosamine [30]. This nanosystem was encapsulated with doxorubicin (DOX), and the results showed that the particle size increased from ca. 500 to ca. 980 nm after decreasing the pH from 9 to 6.5, leading to release DOX-drug within a controlled manner. [PERSON] et al. reported the synthesis of PDEAEMA brushes on mesoporous magnetic nanoparticles and modified them further with folic acid. It was found that ca. 20% and 5% of DOX was released in acidic and basic media, respectively [19].