PEGylated Cisplatin Nanoparticles for Treating Colorectal Cancer in a pH-Responsive Manner
Wei Li1, Yongjun Sun2, Jian Chen1
1Department of General Surgery, The 980th Hospital of the PLA Joint Logistics Support Force (Primary Bethune International Peace Hospital of PLA), Shijiazhuang, 050000 Hebei, China.
Journal of Immunology Research
|August 29, 2022
Summary
This study introduces a novel hyaluronic acid-polyethylene glycol-cisplatin nanoparticle (HA-mPEG-Cis NPs) system. These nanoparticles effectively target colorectal cancer cells, reduce cisplatin toxicity, and demonstrate significant antitumor efficacy in vivo.
Area of Science:
- Nanomedicine
- Oncology
- Drug Delivery Systems
Background:
- Colorectal cancer (CRC) presents a significant global health challenge with high incidence and mortality.
- Conventional cisplatin chemotherapy for CRC lacks tumor specificity and exhibits considerable toxicity, limiting its clinical utility.
- Nanodrug delivery systems offer potential for improved circulation time and enhanced tumor targeting.
Purpose of the Study:
- To synthesize and characterize hyaluronic acid-PEG-cisplatin nanoparticles (HA-mPEG-Cis NPs) for targeted delivery to CD44-positive CRC cells.
- To investigate the pH-responsive drug release and antitumor efficacy of the HA-mPEG-Cis NPs.
- To evaluate the in vivo antitumor performance and safety profile of the novel nanodrug delivery system.
Main Methods:
- Synthesis of HA-mPEG-Cis NPs via self-assembly.
- Characterization of nanoparticle size (48 nm hydrodynamic diameter) and polydispersity (0.13).
- In vitro assessment of pH-responsive cisplatin release, cellular apoptosis, and signaling pathway analysis (PI3K/AKT/mTOR).
- In vivo evaluation of antitumor efficacy in a CT26 cell-bearing mouse model.
Main Results:
- HA-mPEG-Cis NPs demonstrated pH-responsive cisplatin release.
- The nanoparticles induced the highest apoptosis rate (25.1%) in vitro.
- In vivo studies showed significantly reduced tumor volume and weight in the HA-mPEG-Cis NPs group.
- The nanodrug system improved stability and circulation time while reducing cisplatin side effects.
Conclusions:
- The developed pH-responsive HA-mPEG-Cis NPs exhibit promising targeted delivery and enhanced antitumor efficacy against colorectal cancer.
- This nanodrug delivery system offers a rational design strategy to improve cisplatin's therapeutic index by increasing stability and reducing systemic toxicity.
- Further research into this nanomedicine platform holds potential for future clinical applications in cancer therapy.
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