Background: Due to the higher intake of junk food and unhealthy lifestyle, the percentage of U.S. adults aged 50 to 75 years who were up-to-date with colorectal cancer screening increased 1.4 percentage points, from 67.4% in 2016 to 68.8% in 2018. This represents an additional 3.5 million adults screened for colorectal cancer. This is a severe concern of this research, and an attempt was made to prepare a target-specific formulation that could circumvent chemotherapy-related compilation and improvise higher cellular uptake. The fundamental agenda of this research was to prepare and develop Anti-EGFR mAb and 5-Fluorouracil (5-FU) fabricated polymeric nanoparticles for colorectal cancer.

Objective: The main objective of this research was to prepare and evaluate more target specific formulation for the treatment of colorectal cancer. PLGA and PEG-based polymeric nanoparticles are capable of preventing opsonization via the reticuloendothelial system. Hence, prepared polymeric nanoparticles are capable of higher cellular uptake.

Methods: The Poly(d,1-lactide-co-glycolide) (PLGA) and Polyethylene Glycol (PEG) were combined utilizing the ring-opening polymerization method. The presence of PEG prevents opsonization and distinguished blood concentration along with enhanced targeting. The presence of PLGA benefits in the sustained release of polymeric formulations. The optimized formulation (5-FU-PLGA- PEG-NP) was lyophilized using 4% trehalose (cryoprotectants) and conjugated with Anti- EGFR mAb on its surface to produce Anti-EGFR-5-FU-PLGA-PEG-NP; the final formulation, which increases target specificity and drug delivery system of nanoparticles.

Results: The spherical shaped optimized formulation, 5-FU-PLGA-PEG-NP-3 was found to have higher percentage drug entrapment efficacy (71.23%), higher percentage drug content (1.98 ± 0.34%) with minimum particles size (252.3nm) and anionic zeta potential (-31.23mV). The IC₅₀ value of Anti-EGFR-5-FU-PLGA-PEG-NP was 1.01μg/mL after 48 hours incubation period in the HCT 116 cell line, indicating higher anticancer effects of the final formulation.

Conclusion: From the outcomes of various experiments, it was concluded that Anti-EGFR-5-FUPLGA- PEG-NP has biphasic drug release kinetics, higher cellular uptake and higher cytotoxicity. Therefore, anti-EGFR-5-FU-PLGA-PEG-NP holds excellent potential for drug delivery to EGFR positive colorectal cancer cells.

背景：由于垃圾食品摄入量增加和不健康的生活方式，美国 50 至 75 岁成年人及时接受结直肠癌筛查的比例增加了 1.4 个百分点，从 2016 年的 67.4% 增加到 2018 年的 68.8% . 这代表了另外 350 万成年人接受了结肠直肠癌筛查。这是这项研究的一个严重问题，并尝试制备一种靶向特异性制剂，可以规避与化疗相关的汇编并即兴提高细胞摄取。这项研究的基本议程是制备和开发抗 EGFR mAb 和 5-氟尿嘧啶 (5-FU) 制造的用于结直肠癌的聚合物纳米颗粒。

目的：本研究的主要目的是制备和评估治疗结直肠癌的靶向特异性更高的制剂。PLGA 和基于 PEG 的聚合物纳米粒子能够通过网状内皮系统防止调理作用。因此，制备的聚合物纳米粒子能够更高的细胞摄取。

方法：采用开环聚合法将聚（d,1-丙交酯-共-乙交酯）（PLGA）和聚乙二醇（PEG）结合。PEG 的存在可防止调理作用和显着的血液浓度以及增强的靶向性。PLGA 的存在有利于聚合物制剂的持续释放。将优化后的制剂（5-FU-PLGA-PEG-NP）用4%海藻糖（冷冻保护剂）冻干，并在其表面与抗EGFR mAb偶联产生抗EGFR-5-FU-PLGA-PEG-NP；最终配方，增加了纳米颗粒的靶向特异性和药物递送系统。

结果：发现球形优化制剂 5-FU-PLGA-PEG-NP-3 具有更高的药物包封率百分比 (71.23%)、更高的药物含量百分比 (1.98 ± 0.34%) 和最小粒径 (252.3nm) ) 和阴离子 zeta 电位 (-31.23mV)。在 HCT 116 细胞系中孵育 48 小时后，Anti-EGFR-5-FU-PLGA-PEG-NP的 IC ₅₀值为 1.01μg/mL，表明最终制剂具有更高的抗癌效果。

结论：从各种实验的结果可以得出结论，Anti-EGFR-5-FUPLGA-PEG-NP 具有双相药物释放动力学、更高的细胞摄取和更高的细胞毒性。因此，抗 EGFR-5-FU-PLGA-PEG-NP 具有将药物递送至 EGFR 阳性结直肠癌细胞的绝佳潜力。