## 3 Results
### Nanoparticles for Colorectal Cancer Treatment  
Most of the studies included the chemotherapeutic oxaliplatin (OXA) as co-therapy with siRNA. A study performed by [PERSON] et al. (2022) used DAN nanoparticles as the main nanoplatform, assisted by DOTAP and integrated by PEG5k-b-PLGA11k. This research combined this drug with a siRNA targeting ATP7A, which correlated with oxaliplatin resistance in colorectal cancer (CRC) by reducing the intracellular concentration of the drug. The results of this study were exceptional with an improvement in sensitivity for oxaliplatin and reversed chemoresistance of cancer cells with 40% differential cellular viability between the control and the treated cells. In addition, in an in vivo assay these NPs reduced the tumor volume with the synergic therapy by 96.66% compared to the free OXA [22]. Another study performed by [PERSON] et al. (2023) used OXA as co-therapy with the patient's own endocytic primary exosomes loaded with siRNA against CCDC80, which is associated with liver metastasis and CRC chemoresistance. This treatment produced an 85% apoptosis compared to the individualized treatments in cells. Furthermore, xenograft tumor volume was drastically reduced by up to 70% compared to the free drug [23]. [PERSON] et al. (2022) employed a polyamidoamine (PAMAM) dendrimer modified with methoxylpolyethylene glycol (mPEG) and complexed OXA simultaneously with siRNA against ASPN, which promotes chemoresistance by regulating the Wnt/\(\beta\)-catenin signaling  
Figure 1: Flow diagram that represents the articles included in the systematic review. pathway and ABC transporters. It achieved a 25% cell viability reduction gap between the synergic treatment and the one without siRNA in resistant lines. In in vivo assays, it achieved an 80% reduction in tumoral volume and a 5-fold reduction in tumor weight between oxaliplatin alone and synergic treatment [24]. A study by [PERSON] et al. (2022) used oxaliplatin administered individually with silencing therapy (siLDHA) in a cationic polymeric nanoparticle. In this study, a xenograft tumor volume reduction of up to 33.33% was achieved between synergic treatment and OXA alone. It inhibited the M2-like polarization of tumor-associated macrophages (TAM), which was observed in the CD206 population where it was reduced to only 15-26% of the total versus 35% for the single drug [25]. In addition, [PERSON] et al. (2019) developed cationic lipid-assisted nanoparticles, made of biocompatible block copolymers of poly (ethylene glycol) and block-poly (lactic-co-glycolic acid), to carry an siRNA against IDO1 combined with the drug OXA. This protein was involved in the generation of the immunosuppressive microenvironment by inducing apoptosis of cytotoxic T lymphocytes. This therapy achieved a differential reduction of 65.9-70.4% in the size of in vivo tumors treated with synergistic therapy compared to individual treatments, drastically inhibited primary tumor growth and organ metastasis, and increased the percentage of central memory T and effector memory T cells by up to 1% and 3% in tumor site CD4\({}^{*}\) T cells, respectively [26]. Other studies incorporated another drug (simvastatin), like the study carried out by [PERSON] et al. (2023) that used ZIF-8 framework nanoparticles coated with PCBMA (carboxybeleaine methacrylate) and siRNA targeting x-CT. This was a protein of the anti-cystine/glutamate carrier system, related to ferrotopsis. This nanoformulation produced a reduction of 70% in cell viability in vitro, between synergic treatment at the highest concentration and ZIF-8 alone, and a 6-fold and 10-fold reduction in tumor volume and tumor weight, between synergic treatment and ZIF-8 alone, respectively [27]. On the other hand, [PERSON] et al. (2021) developed polymeric nanoparticles, with DSPE-PEG2k on the shell. It was loaded with siRNA against PD-L1 and encapsulated the drugs carboplatin and digitoxin simultaneously.