## 3 In Vivo Applications of MIP-Based DDS
### Targeted DDS  
MIPs are particularly useful in targeted tumor therapy. In addition to loading cytostatic drugs, MIPs can be used for imprinting specific epitopes for the recognition of cancer cells that overexpress specific biomarkers. The resulting dual-imprinted DDS have the ability to specifically recognize and target cancer cells, along with providing a sustained drug delivery at the targeted tissue/organ. Moreover, fluorescent materials or paramagnetic metals can be associated, leading to highly efficient theranostic platforms that combine imaging and targeted drug delivery for safer and more efficient therapeutics [5]. The double-imprinting approach was adopted by [PERSON] et al. for the development of fluorescent MIPs (FMIPs), intended for both targeted recognition and drug delivery. FMIPs were designed by imprinting two different templates: doxorubicin (DOX) and the N-helix terminal epitope of P32 protein, a membrane receptor that is overexpressed on the surface of 4T1 breast cancer cells. DOX-loaded cavities aimed to provide its sustained release, thus reducing potential harmful effects on healthy cells, while the epitope-imprinted sites were meant to specifically recognize, target, and kill the tumor cells which overexpress P32. The core-shell structure design of NPs consisted of an outer imprinted polymer layer prepared via the surface double-imprinting technique, alongside a nucleus-embedded silica NPs. In addition to the numerous advantages of these NPs bringing to the formulation, such as low toxicity, mechanical stability, high solubility, and biocompatibility, it also offers excellent fluorescent properties which subsequently result in the high efficiency of MIPs for targeted fluorescence imaging. In vitro experiments highlighted the major influence pH media had on tumor-targeted drug release, outlined by a 2.7 times greater release of DOX in the typical tumor acidic microenvironment (pH = 6) versus the neutral media (pH = 7.4). Moreover, in vitro cytotoxicity assay emphasized the targeted system's low toxicity and biocompatible characteristics attributed to the silica-core NPs. The complex platform exhibited superior in vivo anticancer effects described by an 0.8 times higher tumor reduction and subsequently revealed a major resemblance between the intravenous and intratumor routes regarding its antitumor efficacy [37]. Paramagnetic metals can also be added to the core-shell NPs for magnetic resonance imaging, gadolinium (Gd) being the most frequently used. Photosensitizers can be additionally loaded for an enhanced therapeutic effect. One paper follows the design and evaluation of a complex MIP-DDS intended for chemo-/photodynamic synergistic targeted cancer therapy. The dual-imprinting technique was selected to obtain MIPs that simultaneously deliver DOX and target an overexpressed biomarker, CD59 protein, represented herein by its epitope. Moreover, the platform was loaded with gadolinium-doped silicon quantum dots for fluorescent/magnetic resonance imaging, along with the chlorin e6 (Ce6) photosensitizer agent. Ce6's mechanism is based on generating reactive oxygen species when exposed to laser irradiation (655 nm). These radicals will exhibit localized cytotoxic effects and subsequently act synergistically with DOX by inducing cancer cell apoptosis. Along with the low toxic effects observed in both in vivo/vitro conditions, the DDS possess high biomarker-targeting activity, a superior therapeutic efficacy and a tolerable safety profile, assets that continue to advise in favor of their use as a promising tool in oncology [38]. The properties of MIPs can easily be adjusted by introducing additional co-monomers, such as HEAA, for faster release kinetics in neutral medium [27], or 4-vinylbenzeneboronic acid (4-VBBA), for improved imprinting effect [39]. The cooperation effect of 4-VBBA and MAA on the affinity of CAP imprinted MIPs was demonstrated by [PERSON] et al. [39]. The association of 4-VBBA and MAA was thought to exhibit a higher affinity for the template.