Anti-cancer activity of camptothecin nanocrystals decorated by silver nanoparticles
Honglei Zhan1, Xiaqing Zhou, Yang Cao
1Department of Biomedical Engineering, Chemistry, and Biological Sciences, Charles V. Schaefer School of Engineering and Sciences, Stevens Institute of Technology, Castle Point on Hudson, Hoboken, NJ 07030, USA. jliang2@stevens.edu.
Abstract:
The emergence of multidrug resistant cancer phenotypes dramatically attenuates the efficiency of a variety of anti-cancer drugs. Silver nanoparticles (AgNPs) display excellent anti-cancer activity and dramatic inhibitory effect on drug resistance related proteins like P-glycoprotein (Pgp). Here we developed a novel drug nanocrystal formulation of Camptothecin (CPT), a broad spectrum anti-cancer agent, decorated by AgNPs. The resulting combinational formulation of CPT and AgNPs, named as CPT/Ag nanocrystals, demonstrated excellent dispersion properties and an improved dissolution rate, drug stability and cellular uptake rate. Because CPT nanocrystals are able to bypass Pgp recognition and AgNPs inhibit both Pgp expression and activity, CPT/Ag nanocrystals showed extreme and indiscriminate cytotoxicity against a variety of both drug sensitive and drug resistant cancer cells. Moreover, the quickly and plenty of released CPT from the CPT/Ag nanocrystals triggered by the tumor microenvironment led to a relaxed and cleavable chromatin structure, facilitating DNA damage and apoptotic potential of AgNPs that were subsequently released.
Insights
Silver nanoparticles (AgNPs) combined with Camptothecin (CPT) nanocrystals overcome multidrug resistance in cancer. This novel formulation exhibits potent cytotoxicity against both drug-sensitive and resistant cancer cells.
Area of Science:
- Nanotechnology
- Oncology
- Pharmacology
Background:
- Multidrug resistance (MDR) in cancer significantly limits therapeutic efficacy.
- Silver nanoparticles (AgNPs) show anti-cancer properties and can inhibit drug resistance mechanisms, such as P-glycoprotein (Pgp).
- Camptothecin (CPT) is a potent anti-cancer agent often hindered by MDR.
Purpose of the Study:
- To develop a novel drug nanocrystal formulation combining Camptothecin (CPT) and Silver Nanoparticles (AgNPs).
- To evaluate the efficacy of this CPT/Ag nanocrystal formulation against drug-sensitive and drug-resistant cancer cells.
- To investigate the underlying mechanisms of enhanced cytotoxicity and drug resistance circumvention.
Main Methods:
- Formulation of Camptothecin (CPT) nanocrystals decorated with Silver Nanoparticles (AgNPs).
- Characterization of CPT/Ag nanocrystals for dispersion, dissolution, stability, and cellular uptake.
- Assessment of cytotoxicity against various cancer cell lines, including MDR phenotypes.
- Evaluation of P-glycoprotein (Pgp) inhibition and its impact on drug resistance.
Main Results:
- CPT/Ag nanocrystals exhibited improved dispersion, dissolution, stability, and cellular uptake.
- The formulation demonstrated potent and indiscriminate cytotoxicity against both drug-sensitive and drug-resistant cancer cells.
- AgNPs inhibited P-glycoprotein (Pgp) expression and activity, while CPT nanocrystals bypassed Pgp recognition.
- Tumor microenvironment-triggered CPT release induced chromatin relaxation, enhancing DNA damage and AgNP-mediated apoptosis.
Conclusions:
- The novel CPT/Ag nanocrystal formulation effectively overcomes cancer multidrug resistance.
- This combinational approach offers a promising strategy for enhancing anti-cancer therapy efficacy.
- The synergistic action of CPT and AgNPs provides broad-spectrum cytotoxicity and improved therapeutic potential.
