Lipid-based nanoparticles (LNPs), including solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and polymeric lipid nanoparticles (PLNs), are promising for colorectal cancer (CRC) therapy due to their biodegradability, biocompatibility, reduced toxicity, and customizable functionality. These LNPs can be administered via oral, rectal, intravenous, intratumoral, hepatic artery infusion, and intraperitoneal routes. Optimized formulations and targeting strategies enhance their pharmacokinetic and pharmacodynamic properties, boosting their anti-tumor effects.
Significant progress has been made with LNPs incorporating various drugs like traditional chemotherapy agents, novel anti-cancer drugs, magnetic hyperthermia particles, and nucleic acid medications, showing promising results in CRC models. LNPs can also combine different antitumor agents to overcome resistance to conventional treatments.
However, challenges remain for clinical application, including:
- Industrial Scale-Up: Complex multi-step LNP formulations hinder consistent large-scale production.
- Tumor Microenvironment Complexity: In vitro and in vivo models often fail to replicate the human tumor microenvironment accurately, impacting clinical outcomes.
- Biocompatibility Concerns: Immunogenicity and toxicity issues, including immune responses, hemolysis, thrombosis, and hypersensitivity reactions, need addressing. Replacing PEG lipids with poly sarcosine lipids (pSar) may mitigate some concerns. Comprehensive toxicity assessments and understanding LNP distribution are necessary.
Future research should focus on scalable production methods, better tumor microenvironment modeling, improving biocompatibility, and long-term safety studies. Despite limitations, further research is crucial to refine LNP therapies for CRC, given the global burden of the disease. Progress in this field is essential for the clinical translation of LNPs and advancing CRC treatment.
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