# Polymeric Nanoparticles--Tools in a Drug Delivery System in Selected Cancer Therapies
## 4 Polymeric Nanoparticles in Colorectal Cancer Treatment  
Colorectal cancer (CRC) is classified as the second leading cause of cancer deaths worldwide and categorized as a solid tumor developed from an initial adenoma [38; 39; 40]. The most challenging issue is the therapy of CRC patients. As a result of progression and angiogenesis, a tumor microenvironment (TME) is formed, which makes treatment with currently available cytostatic agents more difficult due to limited access to tumor cells [39]. Standard therapy includes the administration of mixed cytostatic drugs, e.g., oxaliplatin application together with 5-fluorouracil (5-FU), or the use of irinotecan instead of oxaliplatin [41]. In some cases, additional monoclonal antibodies are also used, e.g., bevacizumab, cetuximab or panitumumab [41]. In the case of therapy and administration of medicinal substances in the treatment of CRC, it is necessary to consider and take into account all physiological as well as pathological aspects occurring in this type of malignancy [41]. Due to its location, the administration of anticancer drugs is carried out mainly by injection of a suspension of polymeric nanoparticles loaded with the drug [41]. Most frequently, additional coating with ligands specific for CRC neoplastic cells is used in this case. Another way of drug administration is the oral route, which involves the use of a pH-dependent drug delivery and release system [41]. The drug, when administered orally, overcomes a number of physiological barriers associated with changes in the pH scale. Therefore, for this purpose,  
Figure 4: Comparison of properties of cancer cells used in treatment with polymeric nanoparticles with normal tissue structure: (**A**) normal tissue; (**B**) cancer tissue with microenvironment. Reprinted with permission from Ref. [34]. Copyright 2022 MDPI. polymeric nanoparticles are coated with an enteric layer, which, at higher pH levels, is degraded, so that the drug can be released at a specific location (Figure 5) [41]. The application of chemotherapeutic agents, due to their physicochemical properties, bioavailability and lack of tissue and cell selectivity, results in the patient's normal cells also being destroyed during therapy [41; 42]. Therefore, new methods of delivering a medicinal substance targeting only cancer cells are increasingly being investigated. To achieve this, researchers are attempting to use polymeric nanoparticles as drug delivery systems in colorectal cancer cells due to the small size of the nanoparticles, allowing them to freely penetrate blood vessels and achieve high stability and targeted release of the drug being carried [42]. An in vitro and in vivo study by the team of [PERSON] et al. [43] in 2020 on the SW620 cell line and BALB/c mice showed that the use of PLGA nanoparticles loaded with 5 mg 5-FU and 2 mg perfluorocarbon (PFC) conjugated to EGF (EGF-PLGA@5 FU/PFC NPs) formulated by the double emulsion solvent evaporation method resulted in the targeted delivery of the anticancer agent to tumor cells only via the active mechanism of the polymeric nanoparticle [43]. In addition, this formulation allows the chemoresistance of colorectal cancer cells to be abolished by locally increasing oxygen levels in the vicinity of the tumor tissues [43]. Such studies provide new information on the use of formulations in the delivery of drug combinations with synergistic effects. Consequently, the use of PNPs to deliver chemotherapeutics in CRC may prove crucial in the development of new strategies for targeted anticancer therapy, thereby reducing the adverse effects caused by the use of uracil-based drugs. In most cases, the polymers used to formulate nanoparticles such as d,l-PLGA are additionally coated with PEG in order to prolong their persistence in the circulation, which is important due to the difficulty of accessing tumor cells through the TME present in colorectal cancer [43]. Among polymeric nanoparticles, studies using the biopolymer chitosan for drug delivery systems in CRC can also be found [43].