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<p>Nilotinib tartrate-loaded lactoferrin-functionalized polycaprolactone nanoparticles (NiloT-PCL-Lf-NPs) were developed as a targeted nanotherapeutic for colorectal cancer. Key carcinogenic targets were SRC, EGFR, and PIK3CA; NiloT showed the highest binding affinity to SRC (-8.641 kcal/mol). The optimised NPs showed good colloidal stability and appropriateness for EPR-mediated tumour accumulation (158.7 ± 35.26 nm; -13.9 ± 1.62 mV; PDI 0.183; entrapment 79.38 ± 7.9%, drug loading 7.45 ± 0.57%). Successful drug encapsulation, nilotinib molecular dispersion within the polymeric matrix, enhanced thermal stability, and the creation of uniformly distributed spherical nanoparticles with minimal aggregation were all validated by physicochemical characterization. Following first-order release kinetics (R<sup>2</sup> = 0.9781), the nanoformulation exhibited sustained, pH-responsive drug release, achieving 75.85 ± 2.39% cumulative release at pH 5.5 after 30 h. NiloT-PCL-Lf-NPs had an IC<sub>50</sub> value of 12.51 µg/mL against HT29 colorectal cancer cells, whereas NiloT had an IC<sub>50</sub> value of around 24.53 µg/mL, according to in vitro studies. Flow cytometric studies and fluorescence microscopy verified increased apoptotic populations (35% early apoptosis and 15% late apoptosis), enhanced cellular uptake and regulated ROS-mediated mitochondrial signaling. Anti-inflammatory research revealed reduced cellular migration and suppression of TNF-α, IL-6, and IL-1β production, indicating anti-metastatic potential. In the HET-CAM test, the formulation also demonstrated excellent vascular biocompatibility and antibacterial activity against Escherichia coli, suggesting decreased toxicity and increased biological safety. NiloT-PCL-Lf-NPs effectively combined receptor-mediated uptake, prolonged release, apoptotic control, inflammatory modulation and enhanced biocompatibility into a single multipurpose nanoplatform. These results provide preliminary preclinical data supporting NiloT-PCL-Lf-NPs as a viable targeted nanotherapeutic platform for colorectal cancer, warranting additional in vivo validation.</p> Graphical Abstract <p>NiloT-PCL-Lf-Nps enabled targeted CRC therapy through receptor-mediated uptake and pH-responsive drug release, resulting in enhanced anticancer activity and biocompatibility.</p> <p></p>

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Nilotinib Tartrate Encapsulated Polycaprolactone Polymeric Nanoparticle Fabricated With Lactoferrin for the Treatment of Colorectal Cancer: In-Silico and In-Vitro Investigation

  • 期刊论文

  • 发表日期：

    2026年7月17日

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  • Harsh Tiwari,
  • Sankha Bhattacharya,
  • Vishal Beldar,
  • Rehan Khan,
  • Ajesh Joshi,
  • Suprit D. Saoji

摘要

Nilotinib tartrate-loaded lactoferrin-functionalized polycaprolactone nanoparticles (NiloT-PCL-Lf-NPs) were developed as a targeted nanotherapeutic for colorectal cancer. Key carcinogenic targets were SRC, EGFR, and PIK3CA; NiloT showed the highest binding affinity to SRC (-8.641 kcal/mol). The optimised NPs showed good colloidal stability and appropriateness for EPR-mediated tumour accumulation (158.7 ± 35.26 nm; -13.9 ± 1.62 mV; PDI 0.183; entrapment 79.38 ± 7.9%, drug loading 7.45 ± 0.57%). Successful drug encapsulation, nilotinib molecular dispersion within the polymeric matrix, enhanced thermal stability, and the creation of uniformly distributed spherical nanoparticles with minimal aggregation were all validated by physicochemical characterization. Following first-order release kinetics (R2 = 0.9781), the nanoformulation exhibited sustained, pH-responsive drug release, achieving 75.85 ± 2.39% cumulative release at pH 5.5 after 30 h. NiloT-PCL-Lf-NPs had an IC50 value of 12.51 µg/mL against HT29 colorectal cancer cells, whereas NiloT had an IC50 value of around 24.53 µg/mL, according to in vitro studies. Flow cytometric studies and fluorescence microscopy verified increased apoptotic populations (35% early apoptosis and 15% late apoptosis), enhanced cellular uptake and regulated ROS-mediated mitochondrial signaling. Anti-inflammatory research revealed reduced cellular migration and suppression of TNF-α, IL-6, and IL-1β production, indicating anti-metastatic potential. In the HET-CAM test, the formulation also demonstrated excellent vascular biocompatibility and antibacterial activity against Escherichia coli, suggesting decreased toxicity and increased biological safety. NiloT-PCL-Lf-NPs effectively combined receptor-mediated uptake, prolonged release, apoptotic control, inflammatory modulation and enhanced biocompatibility into a single multipurpose nanoplatform. These results provide preliminary preclinical data supporting NiloT-PCL-Lf-NPs as a viable targeted nanotherapeutic platform for colorectal cancer, warranting additional in vivo validation.

Graphical Abstract

NiloT-PCL-Lf-Nps enabled targeted CRC therapy through receptor-mediated uptake and pH-responsive drug release, resulting in enhanced anticancer activity and biocompatibility.