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Serotonin-Functionalized Vit-E Nanomicelles for Targeting of Irinotecan to Prostate Cancer Cells
Lakshmi Tunki1,2, Ashok Kumar Jangid3, Deep Pooja2
1Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana 500007, India.
Abstract:
Receptor-mediated endocytosis is key in the success of targeted nanomedicines for the treatment of cancer. Various receptors have been explored for the active targeting of anticancer drugs to avoid the drawbacks of conventional anticancer drugs. This research work aimed to investigate the potential of serotonin (ST)-conjugated Vit-E nanomicelles for the targeted delivery of irinotecan hydrochloride (IRI) to human prostate cancer cells. A ST receptor-targeting conjugate was synthesized by conjugating ST and d-α-tocopheryl polyethylene glycol succinate via a two-step synthesis reaction. The developed formulation demonstrated a size of about 14 nm, a negative zeta potential of around -20 mV, a high drug encapsulation efficiency, and sustained drug release over 48 h. Cytotoxicity studies revealed that ST-conjugated, IRI-loaded nanomicelles (IRI-STNM) were not only toxic to human prostate cancer cells but also eradicate these cells present in the form of 3D spheroids. This cytotoxicity of IRI-STNM was mediated through induction of apoptosis, reactive oxygen species generation, change in mitochondrial membrane potential, and inhibition of cell migration. Further, IRI-STNM performed significantly better than the native IRI and nontargeted nanomicelles, which was led by a higher cellular uptake of IRI-STNM, indicating the role of ST in targeting of drug-loaded nanomicelles.
Insights
Serotonin-conjugated nanomicelles effectively deliver irinotecan hydrochloride to prostate cancer cells, demonstrating potent cytotoxicity and targeting capabilities for improved cancer therapy.
Area of Science:
- Nanomedicine
- Cancer Therapy
- Drug Delivery Systems
Background:
- Receptor-mediated endocytosis is crucial for targeted nanomedicine efficacy in cancer treatment.
- Active targeting strategies using specific receptors aim to overcome limitations of conventional chemotherapy.
- Serotonin (ST) receptors present a potential target for enhanced drug delivery.
Purpose of the Study:
- To investigate serotonin (ST)-conjugated Vitamin E nanomicelles for targeted delivery of irinotecan hydrochloride (IRI) to human prostate cancer cells.
- To synthesize and characterize ST-conjugated nanomicelles for irinotecan hydrochloride delivery.
- To evaluate the in vitro efficacy and targeting potential of the developed nanomicelles.
Main Methods:
- Synthesis of ST-conjugated d-α-tocopheryl polyethylene glycol succinate.
- Preparation and characterization of irinotecan hydrochloride-loaded ST-conjugated nanomicelles (IRI-STNM) including size, zeta potential, encapsulation efficiency, and drug release.
- In vitro cytotoxicity assays on human prostate cancer cells and 3D spheroids.
- Assessment of apoptosis, reactive oxygen species generation, mitochondrial membrane potential, and cell migration.
- Cellular uptake studies comparing IRI-STNM with native IRI and non-targeted nanomicelles.
Main Results:
- Developed IRI-STNM exhibited a size of approximately 14 nm and a zeta potential of -20 mV.
- High drug encapsulation efficiency and sustained drug release over 48 hours were observed.
- IRI-STNM demonstrated significant cytotoxicity against human prostate cancer cells, including 3D spheroids.
- Cytotoxicity was mediated by apoptosis induction, increased reactive oxygen species, altered mitochondrial potential, and inhibited cell migration.
- IRI-STNM showed superior performance compared to native IRI and non-targeted nanomicelles due to enhanced cellular uptake, confirming ST-mediated targeting.
Conclusions:
- ST-conjugated Vitamin E nanomicelles are effective carriers for targeted irinotecan hydrochloride delivery to prostate cancer.
- The developed nanomicelles exhibit potent anticancer activity through multiple cytotoxic mechanisms.
- ST-mediated targeting significantly enhances cellular uptake and therapeutic efficacy, highlighting their potential in cancer therapy.
