Novel GnRH analogue decorated paclitaxel and CQDs co-loaded theranostic zein nanoparticles for treatment of breast cancer: Formulation optimization, in vitro and in vivo evaluation.
Leuprorelin-decorated nanoparticles show promise in improving breast cancer treatment efficacy and safety in preclinical models, but human trials are needed to confirm these findings.
Where it sits
this study against the rest of the leuprorelin corpusSummary and findings
The study developed ligand-decorated theranostic zein nanoparticles co-loaded with paclitaxel and carbon quantum dots for breast cancer treatment. Leuprorelin acetate was used as a ligand to enhance targeting and efficacy. The nanoparticles showed improved cytotoxicity and tumor regression in vitro and in vivo compared to uncoated nanoparticles and nab paclitaxel.
Abstract
Breast cancer is a diverse disease with intertumoral as well as intratumoral heterogeneity, which results in different treatment regimens, disease prognosis, and treatment outcomes. This heterogeneity generally arises due to genetic and epigenetic changes. This requires a delivery system that can treat the tumor as well as provide real-time monitoring of the tumor, i.e., size and location. Hence, current research work is focused on the development of biodegradable and cost-effective ligand-decorated theranostic zein nanoparticles (NPs) prepared by co-loading of an imaging agent, i.e., carbon quantum dots (CQDs), and an anticancer drug, paclitaxel (PCT), simultaneously, whereas leuprorelin acetate (LA) was used as a ligand and electrostatically coated on the surface of zein NPs. CQDs and PCT loading inside zein NPs were optimized using a Box-Behnken design. The optimized batch of CQDs and PCT-loaded zein NPs showed a particle size of 154.23 ± 7.51 nm and +19.65 ± 0.26 mV zeta potential, whereas the % entrapment efficiency of PCT and CQDs was found to be >90%. The LA-coated zein NPs showed a better cytotoxicity profile compared to the pure drug and uncoated zein NPs in MCF-7 and MDA-MB-231 cells. The qualitative and quantitative cellular uptake studies showed remarkably higher uptake of LA-coated zein NPs. An in vivo animal study showed that LA-coating acted as a protein corona, which significantly improved the mean blood circulation time and showed a better tumor regression profile than Nab PCT. Overall, ligand-decorated theranostic zein NPs showed a comparatively better pharmacokinetic profile, lower toxicity, and higher efficacy than the marketed nab PCT formulation.
Background
Breast cancer treatment is challenged by the disease's heterogeneity, which affects treatment outcomes and prognosis. Traditional therapies often lack specificity and can result in systemic toxicity. This study aims to address these issues by developing a targeted drug delivery system using theranostic nanoparticles that can simultaneously treat and monitor tumors.
Methods
The study used a Box-Behnken design to optimize the formulation of zein nanoparticles co-loaded with paclitaxel and carbon quantum dots. Leuprorelin acetate was used as a ligand for targeting, and the nanoparticles were evaluated for cytotoxicity in MCF-7 and MDA-MB-231 cell lines. An in vivo animal study assessed the pharmacokinetic profile and tumor regression efficacy.
Results
The optimized nanoparticles had a particle size of 154.23 ± 7.51 nm and a zeta potential of +19.65 ± 0.26 mV. The entrapment efficiency for paclitaxel and CQDs was greater than 90%. The LA-coated nanoparticles exhibited enhanced cytotoxicity and cellular uptake in vitro. In vivo, they showed improved blood circulation time and tumor regression compared to nab paclitaxel.
Interpretation
The study suggests that LA-coated zein nanoparticles may offer a more effective and less toxic alternative to existing breast cancer treatments like nab paclitaxel. However, the findings are based on preclinical models, and clinical significance in humans remains uncertain. The enhanced targeting and pharmacokinetic profile are promising, but further research is needed to confirm these benefits in human trials.
Key findings
- Particle size of 154.23 ± 7.51 nm.
- Zeta potential of +19.65 ± 0.26 mV.
- >90% entrapment efficiency for paclitaxel and CQDs.
- Improved cytotoxicity in MCF-7 and MDA-MB-231 cells.
- Enhanced tumor regression compared to nab paclitaxel.
Limitations
- Animal study, no human data.
- Short-term in vivo evaluation.
- Surrogate endpoints used.
- Not reported in abstract: long-term safety data.