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Rational Design of Bioinspired Lipoprotein System to Improve Penetration in Colorectal Peritoneal Metastases
Yifei Chi1, Yi Lu2, Jingbo Wu3
1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
Abstract:
Chemotherapy of lethal colorectal peritoneal metastases (PM) is notoriously challenged by poor drug delivery efficiency in PM tumors. Inspired by the histopathological examinations of PM tumors from colon cancer patients, a C[RGDfK] peptide-modified bioinspired lipoprotein (R-BLP) system was optimized from 8 formulations with profound penetrating ability in PM tumors of colorectal cancers. Then, a chemotherapeutic 7-ethyl-10-hydroxy-camptothecin (SN38)-loaded R-BLP (termed SR-BLP) was designed to promote their penetration in PM tumors and improve the chemotherapeutic efficacy. In CT26-induced PM models, SR-BLP exhibited better penetration profiles in PM tumors over a counterpart liposomal formulation. SR-BLP treatment produced an 80.03% suppression of PM incidence with obvious DNA damage and topoisomerase I (TOP I) downregulation and caused a 1.78-fold prolongation of survival time. Therefore, the histopathological features-inspired R-BLP provides an encouraging tumor-penetrating delivery platform for the effective chemotherapy of colorectal PM.
Insights
Researchers developed a novel drug delivery system, SR-BLP, to overcome poor drug delivery in colorectal peritoneal metastases (PM). This system significantly improved chemotherapy effectiveness and prolonged survival in preclinical models.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanotechnology
Background:
- Colorectal peritoneal metastases (PM) present significant challenges in chemotherapy due to inefficient drug delivery.
- Targeted drug delivery systems are crucial for improving treatment efficacy in metastatic cancers.
Purpose of the Study:
- To design and optimize a novel tumor-penetrating drug delivery system for colorectal PM.
- To evaluate the efficacy of a chemotherapeutic-loaded system in preclinical models of colorectal cancer.
Main Methods:
- Optimization of a C[RGDfK] peptide-modified bioinspired lipoprotein (R-BLP) system for enhanced tumor penetration.
- Development of SN38-loaded R-BLP (SR-BLP) for improved chemotherapy delivery and efficacy.
- Assessment of SR-BLP penetration, anti-tumor activity, and survival benefits in CT26-induced PM models.
Main Results:
- SR-BLP demonstrated superior penetration in PM tumors compared to conventional liposomes.
- SR-BLP treatment resulted in 80.03% suppression of PM incidence.
- Significant DNA damage, topoisomerase I (TOP I) downregulation, and a 1.78-fold increase in survival time were observed.
Conclusions:
- The histopathology-inspired R-BLP system serves as an effective tumor-penetrating platform for colorectal PM chemotherapy.
- SR-BLP holds promise for enhancing chemotherapeutic efficacy and patient outcomes in metastatic colorectal cancer.
